Studies. Exclusion criteria were major medical/neurological conditions, pregnancy, substance abuse within 6 months of enrollment, and head injury with loss of consciousness. HC were without history of Axis I disorders or family history of psychosis. Cognitive functioning was characterized by the Repeatable Battery for the Assessment of Neuropsychological Status,18 and symptom severity by the Brief Psychiatric Rating Scale.19 fMRI data were acquired using the gradient-recalled echo-planar imaging sequence (repetition time/echo time (TR/TE) = 2,000/25 ms, flip angle = 70? field of view = 192 mm, 6 mm slice thickness, 32 axial slices). An IFIS-SA system (MRI Devices, Corp., Waukesha, WI, USA) running E-Prime (version 1.2, Psychology Software Tools Inc., Sharpsburg, PA, USA) was used to control stimulus delivery and record responses. We used a turbo spin echo sequence with magnetization transfer contrast to visualize the SN and aid in placement of an 1H-MRS voxel (13 ?13 ?13 mm; Figure 2) positioned around the left SN. Following manual shimming, water-suppressed spectra were collected with the point-resolved spectroscopy sequence (TR/TE = 2,000/80 ms, 640 averages; for details see refs 16, 21).Reward taskAfter a training session, subjects performed a probabilistic monetary reward X-396 chemical information Decision task modeled after Rolls et al.20 during fMRI (six runs of 25 trials; Figure 1). Each trial consisted of three conditions (Decision, Decision Display and Reward Presentation). Each condition was displayed in a pseudorandomly jittered fashion lasting 2, 4, or 6 s (total of 10 s per trial). During Decision, participants selected either a large reward of 30?or a smaller reward of 10?by pushing a right or left box. Although the probability of receiving 10?remained constant (0.9), the probability of receiving 30?varied between runs (0.1, 0.33, and 0.9). Participants were informed that the left/right position of the different reward amounts and probability of receiving the reward of buy Vadadustat higher magnitude would change from run to run, but remain constant within a given run. That is, for a given run, the left/right position of the 10?30?choice would not change. During Decision Display, to indicate a response had been made, the color of the box selected changed. During Reward Presentation, the reward magnitude (RM) earned during a given trial (0? 10? or 30? was displayed. Subjects were instructed to sample both sides offered in each run to determine which selection was more advantageous, with the goal of maximizing the amount of money earned. As previously reported,20 subjects took less than 10 trials to adjust to change in probability and develop an expected value (EV) of that run. After the 10th trial of each run, the EV (RM ?probability) for selecting 10?throughout the run was 9?and, based on increasing probability levels, the EVs for selecting 30?were 3? 10? or 27? Thus, after the 10th trial, the task was such that subjects generated PE. PE was calculated as the difference between the RM for each trial and EV for that run (RM – EV; that is, if EV = 9?(0.9 ?10?, but RM = 0? then PE = – 9). PE could take any one of the following values: – 27, – 10, – 9, – 3, 1, 3, 20, and 27.Statistical analysesDemographics and behavioral data. Independent samples’ t-tests and 2tests were used to compare groups on demographic and behavioralImage acquisitionAll scanning was done on a 3 T Siemens Allegra head-only scanner (Siemens, Erlangen, Germany). A high-resolution structural scan w.Studies. Exclusion criteria were major medical/neurological conditions, pregnancy, substance abuse within 6 months of enrollment, and head injury with loss of consciousness. HC were without history of Axis I disorders or family history of psychosis. Cognitive functioning was characterized by the Repeatable Battery for the Assessment of Neuropsychological Status,18 and symptom severity by the Brief Psychiatric Rating Scale.19 fMRI data were acquired using the gradient-recalled echo-planar imaging sequence (repetition time/echo time (TR/TE) = 2,000/25 ms, flip angle = 70? field of view = 192 mm, 6 mm slice thickness, 32 axial slices). An IFIS-SA system (MRI Devices, Corp., Waukesha, WI, USA) running E-Prime (version 1.2, Psychology Software Tools Inc., Sharpsburg, PA, USA) was used to control stimulus delivery and record responses. We used a turbo spin echo sequence with magnetization transfer contrast to visualize the SN and aid in placement of an 1H-MRS voxel (13 ?13 ?13 mm; Figure 2) positioned around the left SN. Following manual shimming, water-suppressed spectra were collected with the point-resolved spectroscopy sequence (TR/TE = 2,000/80 ms, 640 averages; for details see refs 16, 21).Reward taskAfter a training session, subjects performed a probabilistic monetary reward decision task modeled after Rolls et al.20 during fMRI (six runs of 25 trials; Figure 1). Each trial consisted of three conditions (Decision, Decision Display and Reward Presentation). Each condition was displayed in a pseudorandomly jittered fashion lasting 2, 4, or 6 s (total of 10 s per trial). During Decision, participants selected either a large reward of 30?or a smaller reward of 10?by pushing a right or left box. Although the probability of receiving 10?remained constant (0.9), the probability of receiving 30?varied between runs (0.1, 0.33, and 0.9). Participants were informed that the left/right position of the different reward amounts and probability of receiving the reward of higher magnitude would change from run to run, but remain constant within a given run. That is, for a given run, the left/right position of the 10?30?choice would not change. During Decision Display, to indicate a response had been made, the color of the box selected changed. During Reward Presentation, the reward magnitude (RM) earned during a given trial (0? 10? or 30? was displayed. Subjects were instructed to sample both sides offered in each run to determine which selection was more advantageous, with the goal of maximizing the amount of money earned. As previously reported,20 subjects took less than 10 trials to adjust to change in probability and develop an expected value (EV) of that run. After the 10th trial of each run, the EV (RM ?probability) for selecting 10?throughout the run was 9?and, based on increasing probability levels, the EVs for selecting 30?were 3? 10? or 27? Thus, after the 10th trial, the task was such that subjects generated PE. PE was calculated as the difference between the RM for each trial and EV for that run (RM – EV; that is, if EV = 9?(0.9 ?10?, but RM = 0? then PE = – 9). PE could take any one of the following values: – 27, – 10, – 9, – 3, 1, 3, 20, and 27.Statistical analysesDemographics and behavioral data. Independent samples’ t-tests and 2tests were used to compare groups on demographic and behavioralImage acquisitionAll scanning was done on a 3 T Siemens Allegra head-only scanner (Siemens, Erlangen, Germany). A high-resolution structural scan w.
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