Trial Outcomes & Findings for Maximizing the Impact of Neuroplasticity Using Transcranial Electrical Stimulation Study 2 (NCT NCT03896438)

NCT ID: NCT03896438

Last Updated: 2024-09-19

Results Overview

Most participants completed MRI sessions on a 3T scanner located in the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. FC measures how different brain regions change in activation together. We characterized FC using global connectivity from graph theory analysis. We extracted the fMRI time courses from 454 parcellations defined by the 400 S4 Schaefer Atlas (Schaefer et al., 2018) combined with the Melbourne Subcortex Atlas (Tian et al., 2020). We computed the absolute value of the Pearson's correlation for all possible pairs of time series, creating a 454x454 (N x N) connectivity matrix, which was then reduced to 10% most significant connections by subject. We estimated the FC by calculating the node strength for each parcellation, which is the weighted mean of all significant connections, from these connectivity matrices. Finally, we averaged node strength across parcellations to calculate global node strength. Higher values indicate more brain-wide FC.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 12 participants
• Primary outcome timeframe: baseline
• Results posted on: 2024-09-19

Participant Flow

Three participants dropped out before randomization, but completed the baseline session. Due to difficulty with recruitment and retention that led to low numbers, we were unable to conduct any statistical analyses. In addition, two participants were removed from the DPX neuroimaging results due to motion artefacts. One participant was removed from the NBack neuroimaging results due to scanning issues. One participant was removed from UPSA analyses due to missing scores.

Participant milestones

Measure	Right Active-tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Sham tDCS Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Overall Study STARTED	1	4	4
Overall Study COMPLETED	0	1	2
Overall Study NOT COMPLETED	1	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Maximizing the Impact of Neuroplasticity Using Transcranial Electrical Stimulation Study 2

Baseline characteristics by cohort

Measure	Right Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Total n=9 Participants Total of all reporting groups
Age, Continuous	25 years STANDARD_DEVIATION 0 • n=5 Participants	33 years STANDARD_DEVIATION 14.28 • n=7 Participants	42 years STANDARD_DEVIATION 6.48 • n=5 Participants	36.11 years STANDARD_DEVIATION 11.39 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: baseline

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Most participants completed MRI sessions on a 3T scanner located in the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. FC measures how different brain regions change in activation together. We characterized FC using global connectivity from graph theory analysis. We extracted the fMRI time courses from 454 parcellations defined by the 400 S4 Schaefer Atlas (Schaefer et al., 2018) combined with the Melbourne Subcortex Atlas (Tian et al., 2020). We computed the absolute value of the Pearson's correlation for all possible pairs of time series, creating a 454x454 (N x N) connectivity matrix, which was then reduced to 10% most significant connections by subject. We estimated the FC by calculating the node strength for each parcellation, which is the weighted mean of all significant connections, from these connectivity matrices. Finally, we averaged node strength across parcellations to calculate global node strength. Higher values indicate more brain-wide FC.

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Thalamocortical Functional Connectivity (FC)	17.3 a.u. Standard Deviation 1.7	—	18.2 a.u. Standard Deviation 3

PRIMARY outcome

Timeframe: baseline

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Task-dependent thalamocortical connectivity associated with the N-back task was calculated by modeling the block task design together with the thalamic regressor using psychophysiological interaction analysis (PPI). The thalamic regressor is the time series of the mediodorsal thalamus from the Melbourne atlas. The primary analysis focused on the 2-back conditions alone. The PPI analysis calculates the functional connectivity between the mediodorsal thalamus and all other brain regions specifically during 2-back trials. Neural activation related to the thalamic regressor was compared to neural activation during the fixation (no choices made) to normalize the relative activation (z-score). Positive values indicate increased functional connectivity with the thalamus during the 2-back choices. A z-score of zero represents no difference compared to the fixation cross (no choices). We report the average z-score of the PPI regressor within the control network (Yeo et al., 2011).

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Task-dependent Thalamocortical Functional Connectivity (fMRI) During the N-back Task.	-0.21 z-score Standard Deviation 0.27	—	0.02 z-score Standard Deviation 0.39

PRIMARY outcome

Timeframe: baseline

Task-dependent thalamocortical connectivity associated with the Dot Pattern Expectancy (DPX) task demands will be identified by analyzing cue and probe events together with the thalamic regressor using psychophysiological interaction analysis (PPI). The thalamic regressor is the time series of the mediodorsal thalamus from the Melbourne atlas. We examined B-cue related connectivity. The PPI analysis calculates the functional connectivity between the mediodorsal thalamus and all other brain regions specifically during B-cue trials. Neural activation related to the thalamic regressor was compared to neural activation during the fixation (no choices made) to normalize the relative activation (z-score). Positive values indicate increased functional connectivity with the thalamus during the B-cue responses. A z-score of zero represents no difference compared to the fixation cross (no choices). We report the average z-score of the PPI regressor within the control network.

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Task-dependent Thalamocortical Functional Connectivity (fMRI) During the DPX Task.	-0.03 z-score Standard Deviation 0.58	0.45 z-score Standard Deviation 0	-0.02 z-score Standard Deviation 0.37

PRIMARY outcome

Timeframe: baseline

The n-back task measures working memory capacity. The participant is presented with a series of stimuli and instructed to indicate with a button press when the current stimulus matches the stimulus that appeared a pre-determined number (n) of trials before. d' (d prime) will be calculated as a measure of signal detection, which indicates the normalized rate of hits to false positives (d' = z(H) - z(F)). Increase in d' signifies improved signal detection, i.e. a better outcome. A d' near zero indicates a performance at chance, i.e., a poor performance. The range is -4.65 to 4.65

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in N-back Performance	1.45 d-prime score Standard Deviation 0.31	0 d-prime score Standard Deviation 0	1.99 d-prime score Standard Deviation 0.95

PRIMARY outcome

Timeframe: baseline

The Dot Pattern Expectancy (DPX) task is an adaptation of the expectancy AX task that uses pairs of simple dot patterns rather than letter pairs as stimuli. The DPX task will be performed in 3 blocks. Each trial consists of a cue dot pattern followed by a probe dot pattern. Different combinations of cues and probes enable the identification of a specific deficit in a subject's ability to maintain goal-relevant information throughout a trial. Timing will be jittered and each block of the DPX task will consist of 40 trials: 24 AX (60%), 6 AY (15%), 6 BX (15%) and 4 BY (10%). Each block will last 6 minutes. d'-context will be calculated as a measure of signal detection, which indicates the normalized rate of AX hits to BX false positives (d' = z(H) - z(F)). Increase in d' -context signified improved signal detection, i.e. a better outcome. A d' near zero indicates a performance at chance, i.e., a poor performance. The range is -4.65 to 4.65.

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in DPX Performance	2.65 d-prime score Standard Deviation 0.72	2.51 d-prime score Standard Deviation 0	2.78 d-prime score Standard Deviation 0.73

PRIMARY outcome

Timeframe: baseline

Intends to provide a relatively brief evaluation of key cognitive domains relevant to schizophrenia and related disorders. The composite score is reported as a T-score, with a mean of 50 and standard deviation of 10. Higher values indicate greater cognitive functioning.

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score	48.8 T-score Standard Deviation 11.9	48 T-score Standard Deviation 0	53 T-score Standard Deviation 9.7

PRIMARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Most participants completed MRI sessions on a 3T scanner located in the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. FC measures how different brain regions change in activation together. We characterized FC using global connectivity from graph theory analysis. We extracted the fMRI time courses from 454 parcellations defined by the 400 S4 Schaefer Atlas (Schaefer et al., 2018) combined with the Melbourne Subcortex Atlas (Tian et al., 2020). We computed the absolute value of the Pearson's correlation for all possible pairs of time series, creating a 454x454 (N x N) connectivity matrix, which was then reduced to 10% most significant connections by subject. We estimated the FC by calculating the node strength for each parcellation, which is the weighted mean of all significant connections, from these connectivity matrices. Finally, we averaged node strength across parcellations to calculate global node strength. Higher values indicate more brain-wide FC.

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Thalamocortical Functional Connectivity (FC)	17.4 arbitrary units Standard Deviation 2.4	—	18.8 arbitrary units Standard Deviation 2.7

PRIMARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right and left active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Most participants completed MRI sessions on a 3T scanner located in the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. FC measures how different brain regions change in activation together. We characterized FC using global connectivity from graph theory analysis. We extracted the fMRI time courses from 454 parcellations defined by the 400 S4 Schaefer Atlas (Schaefer et al., 2018) combined with the Melbourne Subcortex Atlas (Tian et al., 2020). We computed the absolute value of the Pearson's correlation for all possible pairs of time series, creating a 454x454 (N x N) connectivity matrix, which was then reduced to 10% most significant connections by subject. We estimated the FC by calculating the node strength for each parcellation, which is the weighted mean of all significant connections, from these connectivity matrices. Finally, we averaged node strength across parcellations to calculate global node strength. Higher values indicate more brain-wide FC.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Thalamocortical Functional Connectivity (FC)	16.5 arbitrary units Standard Deviation 3.2	—	—

PRIMARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Task-dependent thalamocortical connectivity associated with the N-back task was calculated by modeling the block task design together with the thalamic regressor using psychophysiological interaction analysis (PPI). The thalamic regressor is the time series of the mediodorsal thalamus from the Melbourne atlas. The primary analysis focused on the 2-back conditions alone. The PPI analysis calculates the functional connectivity between the mediodorsal thalamus and all other brain regions specifically during 2-back trials. Neural activation related to the thalamic regressor was compared to neural activation during the fixation (no choices made) to normalize the relative activation (z-score). Positive values indicate increased functional connectivity with the thalamus during the 2-back choices. A z-score of zero represents no difference compared to the fixation cross (no choices). We report the average z-score of the PPI regressor within the control network (Yeo et al., 2011).

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Task-dependent Thalamocortical Functional Connectivity (fMRI) During the N-back Task.	-0.92 z-score Standard Deviation 0.63	—	-0.03 z-score Standard Deviation 0.58

PRIMARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Task-dependent thalamocortical connectivity associated with the N-back task was calculated by modeling the block task design together with the thalamic regressor using psychophysiological interaction analysis (PPI). The thalamic regressor is the time series of the mediodorsal thalamus from the Melbourne atlas. The primary analysis focused on the 2-back conditions alone. The PPI analysis calculates the functional connectivity between the mediodorsal thalamus and all other brain regions specifically during 2-back trials. Neural activation related to the thalamic regressor was compared to neural activation during the fixation (no choices made) to normalize the relative activation (z-score). Positive values indicate increased functional connectivity with the thalamus during the 2-back choices. A z-score of zero represents no difference compared to the fixation cross (no choices). We report the average z-score of the PPI regressor within the control network (Yeo et al., 2011).

Outcome measures

Measure	Sham tDCS n=1 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=2 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Task-dependent Thalamocortical Functional Connectivity (fMRI) During the N-back Task.	-1.24 z-score Standard Deviation 0	—	-0.38 z-score Standard Deviation 0.01

PRIMARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

PPI regressor (z-score) within Control Network associated with B-cue Task-dependent thalamocortical connectivity associated with the DPX task demands will be identified by analyzing cue and probe events together with the thalamic regressor using psychophysiological interaction analysis (PPI). The thalamic regressor is the time series of the mediodorsal thalmus from the Melbourne atlas (THA-DAm; Tian et al., 2020). Preliminary analysis for the DPX task will examine B-cue related connectivity alone. We report the average z-score of the PPI regressor within the control network (Yeo et al., 2011). Neural activation was normed to calculated z-scores, such that postive values indicate increased connectivity with the thalamus, and negative values indicate decreased connectivity with the thalamus.

Outcome measures

Measure	Sham tDCS n=1 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Task-dependent Thalamocortical Functional Connectivity (fMRI) During the DPX Task.	-0.52 z-score Standard Deviation 0	—	-0.14 z-score Standard Deviation 0.16

PRIMARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

PPI regressor (z-score) within Control Network associated with B-cue Task-dependent thalamocortical connectivity associated with the DPX task demands will be identified by analyzing cue and probe events together with the thalamic regressor using psychophysiological interaction analysis (PPI). The thalamic regressor is the time series of the mediodorsal thalmus from the Melbourne atlas (THA-DAm; Tian et al., 2020). Preliminary analysis for the DPX task will examine B-cue related connectivity alone. We report the average z-score of the PPI regressor within the control network (Yeo et al., 2011). Neural activation was normed to calculated z-scores, such that postive values indicate increased connectivity with the thalamus, and negative values indicate decreased connectivity with the thalamus.

Outcome measures

Measure	Sham tDCS n=1 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=2 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Changes in Task-dependent Thalamocortical Functional Connectivity (fMRI) During the DPX Task.	0.47 z-score Standard Deviation 0	—	0.04 z-score Standard Deviation 0.23

PRIMARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

The n-back task measures working memory capacity. The participant is presented with a series of stimuli and instructed to indicate with a button press when the current stimulus matches the stimulus that appeared a pre-determined number (n) of trials before. d' (d prime) will be calculated as a measure of signal detection, which indicates the normalized rate of hits to false positives (d' = z(H) - z(F)). Increase in d' signifies improved signal detection, i.e. a better outcome. A d' near zero indicates a performance at chance, i.e., a poor performance. The range is -4.65 to 4.65

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in N-back Performance	2.31 d-prime score Standard Deviation 0.61	—	2.71 d-prime score Standard Deviation 1.13

PRIMARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

The n-back task measures working memory capacity. The participant is presented with a series of stimuli and instructed to indicate with a button press when the current stimulus matches the stimulus that appeared a pre-determined number (n) of trials before. d' (d prime) will be calculated as a measure of signal detection, which indicates the normalized rate of hits to false positives (d' = z(H) - z(F)). Increase in d' signifies improved signal detection, i.e. a better outcome. A d' near zero indicates a performance at chance, i.e., a poor performance. The range is -4.65 to 4.65

Outcome measures

Measure	Sham tDCS n=1 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=2 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in N-back Performance	1.81 d-prime score Standard Deviation 0	—	3.81 d-prime score Standard Deviation 0.58

PRIMARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

The Dot Pattern Expectancy (DPX) task is an adaptation of the expectancy AX task that uses pairs of simple dot patterns rather than letter pairs as stimuli. The DPX task will be performed in 3 blocks. Each trial consists of a cue dot pattern followed by a probe dot pattern. Different combinations of cues and probes enable the identification of a specific deficit in a subject's ability to maintain goal-relevant information throughout a trial. Timing will be jittered and each block of the DPX task will consist of 40 trials: 24 AX (60%), 6 AY (15%), 6 BX (15%) and 4 BY (10%). Each block will last 6 minutes. d'-context will be calculated as a measure of signal detection, which indicates the normalized rate of AX hits to BX false positives (d' = z(H) - z(F)). Increase in d' -context signified improved signal detection, i.e. a better outcome. A d' near zero indicates a performance at chance, i.e., a poor performance. The range is -4.65 to 4.65.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in DPX Performance	3.48 d-prime score Standard Deviation 0.08	—	3.42 d-prime score Standard Deviation 0.44

PRIMARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

The Dot Pattern Expectancy (DPX) task is an adaptation of the expectancy AX task that uses pairs of simple dot patterns rather than letter pairs as stimuli. The DPX task will be performed in 3 blocks. Each trial consists of a cue dot pattern followed by a probe dot pattern. Different combinations of cues and probes enable the identification of a specific deficit in a subject's ability to maintain goal-relevant information throughout a trial. Timing will be jittered and each block of the DPX task will consist of 40 trials: 24 AX (60%), 6 AY (15%), 6 BX (15%) and 4 BY (10%). Each block will last 6 minutes. d'-context will be calculated as a measure of signal detection, which indicates the normalized rate of AX hits to BX false positives (d' = z(H) - z(F)). Increase in d' -context signified improved signal detection, i.e. a better outcome. A d' near zero indicates a performance at chance, i.e., a poor performance. The range is -4.65 to 4.65.

Outcome measures

Measure	Sham tDCS n=1 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=2 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in DPX Performance	1.57 d-prime score Standard Deviation 0	—	3.68 d-prime score Standard Deviation 0.11

PRIMARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

MCCB Composite T-Score Intends to provide a relatively brief evaluation of key cognitive domains relevant to schizophrenia and related disorders. The composite score is reported as a T-score, with a mean of 50 and standard deviation of 10. Higher values indicate greater cognitive functioning.

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score	49.7 T-score Standard Deviation 18.6	—	48.33 T-score Standard Deviation 8.5

PRIMARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

MCCB Composite T-Score Intends to provide a relatively brief evaluation of key cognitive domains relevant to schizophrenia and related disorders. The composite score is reported as a T-score, with a mean of 50 and standard deviation of 10. Higher values indicate greater cognitive functioning.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score	69.5 T-score Standard Deviation 4.9	—	42 T-score Standard Deviation 0

PRIMARY outcome

Timeframe: follow-up (week 24)

Population: We had difficulty with recruitment, so there were zero people that completed the right and left active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

MCCB Composite T-Score Intends to provide a relatively brief evaluation of key cognitive domains relevant to schizophrenia and related disorders. The composite score is reported as a T-score, with a mean of 50 and standard deviation of 10. Higher values indicate greater cognitive functioning.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) Composite Score	68 T-score Standard Deviation 2.8	—	—

SECONDARY outcome

Timeframe: baseline

Measures functional capacity by assessing skills involved in everyday tasks important to daily living. Points are scored for each of two sub scales based on the participant's correct performance of items in the sub scale (incorrect: 0 points, correct: 1 or 2 points). Points are used to derive a sub scale score by dividing points scored by the number of items in the sub scale (percentage correct) and multiplied by 50. The two sub scale scores are then added to derive the total score, with a possible range of 0-100. Higher scores represent better outcomes.

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in University of California San Diego Performance-Based Skills Assessment - Brief (UPSA-B)	76.3 raw score Standard Deviation 6.8	84 raw score Standard Deviation 0	85.5 raw score Standard Deviation 7.9

SECONDARY outcome

Timeframe: baseline

Measures symptom severity in patients with schizophrenia. Scores are assigned for symptom categories based on a semi-structured clinical interview with anchored severity scales (1-7) for each symptom category. Total score is derived by adding up individual symptom scores, resulting in a total score range of 24-168. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Psychiatric Rating Scale (BPRS) Score	53.3 raw score Standard Deviation 8.5	33 raw score Standard Deviation 0	51.5 raw score Standard Deviation 9.7

SECONDARY outcome

Timeframe: baseline

Measures of symptom severity in patients with schizophrenia with an emphasis on negative symptoms. Scores are assigned to symptom categories based on a semi-structured clinical interview with anchored severity scales (0-6 or 0-9). Total score is derived by adding up individual symptom scores, resulting in a total score range of 0-90. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Negative Symptom Scale (BNSS) Score	12.5 raw score Standard Deviation 10.7	5 raw score Standard Deviation 0	9.25 raw score Standard Deviation 7.04

SECONDARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures functional capacity by assessing skills involved in everyday tasks important to daily living. Points are scored for each of two sub scales based on the participant's correct performance of items in the sub scale (incorrect: 0 points, correct: 1 or 2 points). Points are used to derive a sub scale score by dividing points scored by the number of items in the sub scale (percentage correct) and multiplied by 50. The two sub scale scores are then added to derive the total score, with a possible range of 0-100. Higher scores represent better outcomes.

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in University of California San Diego Performance-Based Skills Assessment - Brief (UPSA-B)	61.3 raw score Standard Deviation 7.1	—	83 raw score Standard Deviation 4.3

SECONDARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures functional capacity by assessing skills involved in everyday tasks important to daily living. Points are scored for each of two sub scales based on the participant's correct performance of items in the sub scale (incorrect: 0 points, correct: 1 or 2 points). Points are used to derive a sub scale score by dividing points scored by the number of items in the sub scale (percentage correct) and multiplied by 50. The two sub scale scores are then added to derive the total score, with a possible range of 0-100. Higher scores represent better outcomes.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in University of California San Diego Performance-Based Skills Assessment - Brief (UPSA-B)	82.5 raw score Standard Deviation 3.5	—	80 raw score Standard Deviation 0

SECONDARY outcome

Timeframe: follow-up (week 24)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures functional capacity by assessing skills involved in everyday tasks important to daily living. Points are scored for each of two sub scales based on the participant's correct performance of items in the sub scale (incorrect: 0 points, correct: 1 or 2 points). Points are used to derive a sub scale score by dividing points scored by the number of items in the sub scale (percentage correct) and multiplied by 50. The two sub scale scores are then added to derive the total score, with a possible range of 0-100. Higher scores represent better outcomes.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in University of California San Diego Performance-Based Skills Assessment - Brief (UPSA-B)	74.5 raw score Standard Deviation 7.8	—	85 raw score Standard Deviation 0

SECONDARY outcome

Timeframe: mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures symptom severity in patients with schizophrenia. Scores are assigned for symptom categories based on a semi-structured clinical interview with anchored severity scales (1-7) for each symptom category. Total score is derived by adding up individual symptom scores, resulting in a total score range of 24-168. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Psychiatric Rating Scale (BPRS) Score	49 raw score Standard Deviation 8.2	—	55 raw score Standard Deviation 9

SECONDARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures symptom severity in patients with schizophrenia. Scores are assigned for symptom categories based on a semi-structured clinical interview with anchored severity scales (1-7) for each symptom category. Total score is derived by adding up individual symptom scores, resulting in a total score range of 24-168. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Psychiatric Rating Scale (BPRS) Score	40.5 raw score Standard Deviation 4.9	—	50 raw score Standard Deviation 0

SECONDARY outcome

Timeframe: follow-up (week 24)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures symptom severity in patients with schizophrenia. Scores are assigned for symptom categories based on a semi-structured clinical interview with anchored severity scales (1-7) for each symptom category. Total score is derived by adding up individual symptom scores, resulting in a total score range of 24-168. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Psychiatric Rating Scale (BPRS) Score	30 raw score Standard Deviation 5.6	—	37 raw score Standard Deviation 0

SECONDARY outcome

Timeframe: baseline

Measures of symptom severity in patients with schizophrenia with an emphasis on negative symptoms. Scores are assigned to symptom categories based on a semi-structured clinical interview with anchored severity scales (0-6 or 0-9). Total score is derived by adding up individual symptom scores, resulting in a total score range of 0-90. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=4 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Negative Symptom Scale (BNSS) Score	12.5 raw score Standard Deviation 10.7	5 raw score Standard Deviation 0	9.25 raw score Standard Deviation 7.04

SECONDARY outcome

Timeframe: Mid-test (week 6)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures of symptom severity in patients with schizophrenia with an emphasis on negative symptoms. Scores are assigned to symptom categories based on a semi-structured clinical interview with anchored severity scales (0-6 or 0-9). Total score is derived by adding up individual symptom scores, resulting in a total score range of 0-90. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=3 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=3 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Negative Symptom Scale (BNSS) Score	14 raw score Standard Deviation 8.9	—	7.3 raw score Standard Deviation 6.8

SECONDARY outcome

Timeframe: post-test (week 12)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures of symptom severity in patients with schizophrenia with an emphasis on negative symptoms. Scores are assigned to symptom categories based on a semi-structured clinical interview with anchored severity scales (0-6 or 0-9). Total score is derived by adding up individual symptom scores, resulting in a total score range of 0-90. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Negative Symptom Scale (BNSS) Score	12.5 raw score Standard Deviation 10.6	—	20 raw score Standard Deviation 0

SECONDARY outcome

Timeframe: follow-up (week 24)

Population: We had difficulty with recruitment, so there were zero people that completed the right active-tDCS for this attribute, and therefore we cannot report anything for the mean (there is no value)

Measures of symptom severity in patients with schizophrenia with an emphasis on negative symptoms. Scores are assigned to symptom categories based on a semi-structured clinical interview with anchored severity scales (0-6 or 0-9). Total score is derived by adding up individual symptom scores, resulting in a total score range of 0-90. Higher scores indicate greater symptom severity. A decrease in scores over time would indicate symptom reduction, i.e. a better outcome.

Outcome measures

Measure	Sham tDCS n=2 Participants Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Right Active tDCS 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=1 Participants 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
Change in Brief Negative Symptom Scale (BNSS) Score	17 raw score Standard Deviation 11.3	—	13 raw score Standard Deviation 0

Adverse Events

Right Active-tDCS

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Left Active-tDCS

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sham tDCS

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Right Active-tDCS n=1 participants at risk 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA right (AF4 anode - AF3 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Left Active-tDCS n=4 participants at risk 2-3 times/week for 12 weeks: ramp-up for 30 seconds, 2mA left (AF3 anode - AF4 cathode) for 20 min, and then ramp-down for 30 seconds. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.	Sham tDCS n=4 participants at risk Current will be turned off immediately after the initial 30-second ramp-up period. Transcranial Direct Current Stimulation (tDCS): Three different stimulation montages will be programmed: right, left and sham. During the Ramp periods, 2 mA current will be delivered to both AF3 and AF4 with an ascending (RampUp) and descending ramp (RampDown) over 30 sec via two saline soaked electrode sponges (\~ 25cm²; current density = 0.08 mA/cm²). In this way, all subjects experience the same sensation on both sides to blind them to condition. During the Constant period, current will be set based on the Condition: Right - 2mA AF4 anode-AF3 cathode; Left - 2mA applied to AF3 anode-AF4 cathode; Sham - current turned off.
General disorders Burn from tDCS electrode	0.00% 0/1 • 12 weeks	25.0% 1/4 • Number of events 1 • 12 weeks	0.00% 0/4 • 12 weeks
General disorders Reported brain fog(moderate or greater)	0.00% 0/1 • 12 weeks	50.0% 2/4 • Number of events 2 • 12 weeks	0.00% 0/4 • 12 weeks

Additional Information

Melanie Stimac

University of Minnesota

Phone: 612-301-2449

Email: stima011@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place