Widespread white matter microstructural differences in schizophrenia across 4322 individuals:Results from the ENIGMA Schizophrenia DTI Working Group

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.Molecular Psychiatry advance online publication, 17 October 2017; doi:10.1038/mp.2017.170

Decoding emotional prosody: Resolving differences in functional neuroanatomy from fMRI & lesion studies using TMS

BackgroundProsody conveys information about the emotional state and intention of others. Lesion studies have shown that damage to the right posterior temporal region is associated with prosody decoding deficits. Dissimilarly to findings from lesion studies, neuroimaging data show substantial bilateral peri-Sylvian activation.ObjectiveThis study aimed to investigate the involvement of the left and right superior temporal gyrus (STG) in prosodic and semantic processing using transcranial magnetic stimulation (TMS). These two regions of interest were chosen for their correspondence to Wernicke’s area in the left hemisphere and its analog in the right.MethodsOffline TMS with a stimulation frequency of 1 Hz and intensity of 60% of stimulator output (approximately 1.1 Tesla) with one pulse applied per second for 10 minutes (600 pulses) was performed. Directly after TMS on the right STG, the left STG or sham-stimulation, participants completed a prosody decoding or a semantic judgment task (whether the tone/meaning was happy or sad).ResultsReaction times (RT) for the prosodic task were significantly slower when TMS was applied in the right STG in comparison to left STG and sham conditions. TMS over both right and left STG delayed RT in the semantic task, significantly when the tone of voice was incongruent with the meaning.ConclusionsOur data strongly suggests that left temporal regions are not crucial to the basic task of prosody decoding per se; however, the analogous region on the right is. Hence, involvement of the left STG in prosodic decoding revealed in previous imaging data is incidental

Dissociable Effects of Cocaine Dependence on Reward Processes: The Role of Acute Cocaine and Craving

The relative impact of chronic vs acute cocaine on dependence-related variability in reward processing in cocaine-dependent individuals (CD) is not well understood, despite the relevance of such effects to long-term outcomes. To dissociate these effects, CD (N=15) and healthy controls (HC; N=15) underwent MRI two times while performing a monetary incentive delay task. Both scans were identical across subjects/groups, except that, in a single-blind, counterbalanced design, CD received intravenous cocaine (30 mg/70 kg) before one session (CD+cocaine) and saline in another (CD+saline). Imaging analyses focused on activity related to anticipatory valence (gain/loss), anticipatory magnitude (small/medium/large), and reinforcing outcomes (successful/unsuccessful). Drug condition (cocaine vs saline) and group (HC vs CD+cocaine or CD+saline) did not influence valence-related activity. However, compared with HC, magnitude-related activity for gains was reduced in CD in the left cingulate gyrus post-cocaine and in the left putamen in the abstinence/saline condition. In contrast, magnitude-dependent activity for losses increased in CD vs HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-saline. Across outcomes (ie, successful and unsuccessful) activity in the right habenula decreased in CD in the abstinence/saline condition vs acute cocaine and HC. Cocaine-dependent variability in outcome- and loss-magnitude activity correlated negatively with ratings of cocaine craving and positively with how high subjects felt during the scanning session. Collectively, these data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-related insensitivity to reinforcing outcomes/‘liking', but having no discernible effect on dependence-related alterations in incentive salience/‘wanting'. The relationship of drug-related affective sequelae to non-drug reward processing suggests that CD experience a general alteration of reward function and may be motivated to continue using cocaine for reasons beyond desired drug-related effects. This may have implications for individual differences in treatment efficacy for approaches that rely on reinforcement strategies (eg, contingency management) and for the long-term success of treatment