Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent brain function that can be associated with clinical variables or modulated by interventions such as behavioral training or pharmacological manipulations. These biomarkers include time-averaged regional brain function as manifested by regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion MRI and correlated temporal fluctuations of function across brain networks with either ASL or blood oxygenation level dependent (BOLD) fMRI. Resting-state studies are typically carried out using just one of several prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual fixation on a cross-hair (FIX), which may affect the reliability and specificity of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting-state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance task), and examined the effects of these task conditions on reliability and reproducibility as well as trait specificity of regional brain function. We also acquired resting-state BOLD fMRI under FIX and compared the network connectivity reliabilities between the four ASL conditions and the BOLD FIX condition. For resting-state ASL data, EC provided the highest CBF reliability, reproducibility, trait specificity, and network connectivity reliability, followed by EO, while FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability, reproducibility and trait specificity than EO and EC. Overall network connectivity reliability was comparable between ASL and BOLD. Our findings confirm ASL CBF as a reliable, stable, and consistent measure of resting-state regional brain function and support the use of EC or EO over FIX and PVT as the resting-state condition.

Excessive discounting of future rewards has been related to a variety of risky behaviors and adverse clinical conditions. Prior work examining delay discounting in schizophrenia suggests an elevated discount rate. However, it remains uncertain whether this reflects the disease process itself or an underlying genetic vulnerability, whether it is selective for delay discounting or reflects pervasive changes in decision-making, and whether it is driven by specific clinical dimensions such as cognitive impairment. Here we investigated delay discounting, as well as loss aversion and risk aversion, in three groups: schizophrenia (SZ), unaffected first degree family members (FM), and controls without a family history of psychosis (NC). SZ had elevated discounting, without changes in loss aversion or risk aversion. Contrary to expectations, the FM group did not show an intermediate phenotype in discounting. Higher discount rates correlated with lower cognitive performance on verbal reasoning, but this did not explain elevated discount rates in SZ. Group differences were driven primarily by the non-smoking majority of the sample. This study provides further evidence for elevated discounting in schizophrenia, and demonstrates that steeper discounting is not necessarily associated with familial risk, cannot be wholly accounted for by cognitive deficits, and is not attributable to smoking related impulsivity.

OBJECTIVE Anhedonia is central to multiple psychiatric disorders and causes substantial disability. A dimensional conceptualization posits that anhedonia severity is related to a transdiagnostic continuum of reward deficits in specific neural networks. Previous functional connectivity studies related to anhedonia have focused on case-control comparisons in specific disorders, using region-specific seed-based analyses. Here, the authors explore the entire functional connectome in relation to reward responsivity across a population of adults with heterogeneous psychopathology. METHOD In a sample of 225 adults from five diagnostic groups (major depressive disorder, N=32; bipolar disorder, N=50; schizophrenia, N=51; psychosis risk, N=39; and healthy control subjects, N=53), the authors conducted a connectome-wide analysis examining the relationship between a dimensional measure of reward responsivity (the reward sensitivity subscale of the Behavioral Activation Scale) and resting-state functional connectivity using multivariate distance-based matrix regression. RESULTS The authors identified foci of dysconnectivity associated with reward responsivity in the nucleus accumbens, the default mode network, and the cingulo-opercular network. Follow-up analyses revealed dysconnectivity among specific large-scale functional networks and their connectivity with the nucleus accumbens. Reward deficits were associated with decreased connectivity between the nucleus accumbens and the default mode network and increased connectivity between the nucleus accumbens and the cingulo-opercular network. In addition, impaired reward responsivity was associated with default mode network hyperconnectivity and diminished connectivity between the default mode network and the cingulo-opercular network. CONCLUSIONS These results emphasize the centrality of the nucleus accumbens in the pathophysiology of reward deficits and suggest that dissociable patterns of connectivity among large-scale networks are critical to the neurobiology of reward dysfunction across clinical diagnostic categories.

Background: Amotivation, or decisional anhedonia, is a prominent and disabling feature of depression. However, this aspect of depression remains understudied, and no prior work has applied objective laboratory tests of motivation in both unipolar and bipolar depression.Methods: We assessed motivation deficits using a Progressive Ratio Task (PRT) that indexes willingness to exert effort for monetary reward. The PRT was administered to 96 adults ages 18-60 including 25 participants with a current episode of unipolar depression, 28 with bipolar disorder (current episode depressed), and 43 controls without any Axis I psychiatric disorders.Results: Depressed participants exhibited significantly lower motivation than control participants as objectively defined by progressive ratio breakpoints. Both the unipolar and bipolar groups were lower than controls but did not differ from each other.Limitations: Medication use differed across groups, and we did not have a separate control task to measure psychomotor activity; however neither medication effects or psychomotor slowing are likely to explain our findings.Conclusions: Our study fills an important gap in the literature by providing evidence that diminished effort on the PRT is present across depressed patients who experience either unipolar or bipolar depression. This adds to growing evidence for shared mechanisms of reward and motivation dysfunction, and highlights the importance of improving the assessment and treatment of motivation deficits across the mood disorders spectrum. (C) 2016 Elsevier B.V. All rights reserved.

Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain’s reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.

Motivational deficits play a central role in disability caused by schizophrenia and constitute a major unmet therapeutic need. Negative symptoms have previously been linked to hypofunction in ventral striatum (VS), a core component of brain motivation circuitry. However, it remains unclear to what extent this relationship holds for specific negative symptoms such as amotivation, and this question has not been addressed with integrated behavioral, clinical, and imaging measures. Here, 41 individuals with schizophrenia and 37 controls performed a brief, computerized progressive ratio task (PRT) that quantifies effort exerted in pursuit of monetary reward. Clinical amotivation was assessed using the recently validated Clinical Assessment Interview for Negative Symptoms (CAINS). VS function was probed during functional magnetic resonance imaging using a monetary guessing paradigm. We found that individuals with schizophrenia had diminished motivation as measured by the PRT, which significantly and selectively related to clinical amotivation as measured by the CAINS. Critically, lower PRT motivation in schizophrenia was also dimensionally related to VS hypofunction. Our results demonstrate robust dimensional associations between behavioral amotivation, clinical amotivation, and VS hypofunction in schizophrenia. Integrating behavioral measures such as the PRT will facilitate translational efforts to identify biomarkers of amotivation and to assess response to novel therapeutic interventions.

Neuroimaging studies of mood disorders demonstrate abnormalities in brain regions implicated in reward processing. However, there is a paucity of research investigating how social rewards affect reward circuit activity in these disorders. Here, we evaluated the relationship of both diagnostic category and dimensional depression severity to reward system function in bipolar and unipolar depression. In total, 86 adults were included, including 24 patients with bipolar depression, 24 patients with unipolar depression, and 38 healthy comparison subjects. Participants completed a social reward task during 3T BOLD fMRI. On average, diagnostic groups did not differ in activation to social reward. However, greater depression severity significantly correlated with reduced bilateral ventral striatum activation to social reward in the bipolar depressed group, but not the unipolar depressed group. In addition, decreased left orbitofrontal cortical activation correlated with more severe symptoms in bipolar depression, but not unipolar depression. These differential dimensional effects resulted in a significant voxelwise group by depression severity interaction. Taken together, these results provide initial evidence that deficits in social reward processing are differentially related to depression severity in the two disorders.