O determine the relationship between observed eventrelated blood oxygen level-dependent (BOLD) signal and regressors representing expected neural responses to trial events. To examine the effects of reward separate from learning, the first 10 trials of each run were excluded from analysis.20 Decision events (at the time of button press) and reward presentations (at the midpoint of the reward presentation window) were modeled as stick functions in the general linear model along with their first-order temporal derivatives. In addition, in order to identify regions where the BOLD signal changed as a function of PE, reward presentation events were parametrically modulated (correlated) by their respective PE, with values ranging from – 27 to 27. The first-order PEH-MRSH-MRS data were quantified in the time domain, incorporating prior knowledge AUY922 mechanism of action derived from in vitro and in vivo metabolite spectra (for details see refs 25?7). Cramer-Rao lower bounds, an estimate of uncertainty, were calculated for each peak; data with Cramer-Rao lower bounds 430 were excluded. Glx was quantified with respect to creatine, and will hereafter be referred to as Glx. Spectroscopy data were not obtained in 1 SZ completing the reward task, spectral quality was poor in 4 HC and 5 SZ, and 1 SZ was excluded as an outlier (43 s.d. above mean), leaving 15 HC and 15 SZ in analyses involving Glx. An analysis of covariance with age and smoking as covariates was performed to assess group differences in Glx.Combined fMRI/MRSRegression analyses were performed in SPM8 to identify regions in the midbrain/SN and ventral striatum where the linear relationship between PE and BOLD during Reward Presentation was correlated with SN Glx. The analysis was performed in HC and SZ using the same masks as above withTable 1.Demographics, clinical measures, and task performancea SZ (n = 22) HC (n = 19) 57.9 36.47 (12.12) 7.50 (4.76) 42.1 0.36 (0.50) t/X2 1.77 – 0.74 12.52 4.82 – 1.74 P-value 0.31 0.47 0.25 0.03 0.Gender ( male) Age Parental occupationb Smoking status ( smokers) Smoking (packs per day) Diagnosis Schizophrenia Schizoaffective disorder Illness duration (in years) Antipsychotic medication First generation Second generation First and second generations Clozapinec BPRSd Total Positive Negative RBANS total index Prediction error task Total reward earned ( ) Mean prediction error ( ) Task performancee77.3 39.41 (6.70) 6.70 (5.05) 72.7 0.66 (0.60) 15 7 17.68 (11.53) 2 17 1 2 30.27 5.77 4.27 76.14 (8.86) (3.74) (1.75) (9.33)93.32 (11.49) 12.41 (1.14) – 0.31 (0.33) 0.01 (0.02)5.28 1.59 – 1.13 2.32fo 0.01 0.12 0.26 0.11.71 (1.59) – 0.19 (0.33) 0.03 (0.01)Abbreviations: HC, healthy controls; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; SZ, schizophrenia. a Mean (s.d.) unless indicated otherwise. b Ranks determined from Diagnostic Interview for Genetic Studies (1?8 scale); higher rank (lower numerical value) corresponds to higher socioeconomic status. Parental occupation unknown in three HC and two patients with schizophrenia, n = 36. c One SZ with clozapine monotherapy and one SZ with combination of clozapine and ziprasidone. d Brief Psychiatric Rating Scale (1? scale); positive (conceptual disorganization, hallucinatory behavior, and unusual thought content); negative (AZD0156 custom synthesis emotional withdrawal, motor retardation, and blunted affect). e To assess diagnostic status as predictor of trial response, linear regression was conducted (button press as dependent variabl.O determine the relationship between observed eventrelated blood oxygen level-dependent (BOLD) signal and regressors representing expected neural responses to trial events. To examine the effects of reward separate from learning, the first 10 trials of each run were excluded from analysis.20 Decision events (at the time of button press) and reward presentations (at the midpoint of the reward presentation window) were modeled as stick functions in the general linear model along with their first-order temporal derivatives. In addition, in order to identify regions where the BOLD signal changed as a function of PE, reward presentation events were parametrically modulated (correlated) by their respective PE, with values ranging from – 27 to 27. The first-order PEH-MRSH-MRS data were quantified in the time domain, incorporating prior knowledge derived from in vitro and in vivo metabolite spectra (for details see refs 25?7). Cramer-Rao lower bounds, an estimate of uncertainty, were calculated for each peak; data with Cramer-Rao lower bounds 430 were excluded. Glx was quantified with respect to creatine, and will hereafter be referred to as Glx. Spectroscopy data were not obtained in 1 SZ completing the reward task, spectral quality was poor in 4 HC and 5 SZ, and 1 SZ was excluded as an outlier (43 s.d. above mean), leaving 15 HC and 15 SZ in analyses involving Glx. An analysis of covariance with age and smoking as covariates was performed to assess group differences in Glx.Combined fMRI/MRSRegression analyses were performed in SPM8 to identify regions in the midbrain/SN and ventral striatum where the linear relationship between PE and BOLD during Reward Presentation was correlated with SN Glx. The analysis was performed in HC and SZ using the same masks as above withTable 1.Demographics, clinical measures, and task performancea SZ (n = 22) HC (n = 19) 57.9 36.47 (12.12) 7.50 (4.76) 42.1 0.36 (0.50) t/X2 1.77 – 0.74 12.52 4.82 – 1.74 P-value 0.31 0.47 0.25 0.03 0.Gender ( male) Age Parental occupationb Smoking status ( smokers) Smoking (packs per day) Diagnosis Schizophrenia Schizoaffective disorder Illness duration (in years) Antipsychotic medication First generation Second generation First and second generations Clozapinec BPRSd Total Positive Negative RBANS total index Prediction error task Total reward earned ( ) Mean prediction error ( ) Task performancee77.3 39.41 (6.70) 6.70 (5.05) 72.7 0.66 (0.60) 15 7 17.68 (11.53) 2 17 1 2 30.27 5.77 4.27 76.14 (8.86) (3.74) (1.75) (9.33)93.32 (11.49) 12.41 (1.14) – 0.31 (0.33) 0.01 (0.02)5.28 1.59 – 1.13 2.32fo 0.01 0.12 0.26 0.11.71 (1.59) – 0.19 (0.33) 0.03 (0.01)Abbreviations: HC, healthy controls; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; SZ, schizophrenia. a Mean (s.d.) unless indicated otherwise. b Ranks determined from Diagnostic Interview for Genetic Studies (1?8 scale); higher rank (lower numerical value) corresponds to higher socioeconomic status. Parental occupation unknown in three HC and two patients with schizophrenia, n = 36. c One SZ with clozapine monotherapy and one SZ with combination of clozapine and ziprasidone. d Brief Psychiatric Rating Scale (1? scale); positive (conceptual disorganization, hallucinatory behavior, and unusual thought content); negative (emotional withdrawal, motor retardation, and blunted affect). e To assess diagnostic status as predictor of trial response, linear regression was conducted (button press as dependent variabl.
