Haste or Speed? Alterations in the Impact of Incentive Cues on Task Performance in Remitted and Depressed Patients With Bipolar Disorder

A variety of evidence suggests that bipolar disorder is associated with disruptions of reward related processes, although the properties, and scope of these changes are not well understood. In the present study, we aimed to address this question by examining performance of patients with bipolar disorder (30 depressed bipolar; 35 euthymic bipolar) on a motivated choice reaction time task. We compared performance with a group of healthy control individuals (n = 44) and a group of patients with unipolar depression (n = 41), who were matched on several demographic variables. The task consists of an “odd-one-out” discrimination, in the presence of a cue signaling the probability of reward on a given trial (10, 50, or 90%) given a sufficiently fast response. All groups showed similar reaction time (RT) performance, and similar shortening of RT following the presentation of a reward predictive cue. However, compared to healthy individuals, the euthymic bipolar group showed a relative increase in commission errors during the high reward compared to low condition. Further correlational analysis revealed that in the healthy control and unipolar depression groups, participants tended either to shorten RTs for the high rather than low reward cue a relatively large amount with an increase in error rate, or to shorten RTs to a lesser extent but without increasing errors to the same degree. By contrast, reward-related speeding and reward-related increase in errors were less well coupled in the bipolar groups, significantly so in the BPD group. These findings suggest that although RT performance on the present task is relatively well matched, there may be a specific failure of individuals with bipolar disorder to calibrate RT speed and accuracy in a strategic way in the presence of reward-related stimuli

Enhanced brainstem cerebral blood flow accompanies symptoms of anhedonia in young adults

Study: Midbrain serotonergic projections are of crucial theoretical significance for mood disorders. Furthermore, learned helplessness (LH) is associated with enhanced metabolic activity in rodent serotonergic midbrain models. However, little evidence supports serotonergic projections in predicting illness severity. We employed arterial spin labeling (ASL) to measure whole brain cerebral blood flow (CBF) in distressed and healthy individuals varying in anxiety and anhedonia. Methods: 36 distressed (27 females; mean age=22.2, SD=2.1) and 34 healthy (19 females; mean age=21.5, SD=1.8) individuals underwent a resting acquisition. Blood flow was measured using a multiband pseudo continuous ASL sequence. Regional cerebral perfusion data was collected with 25 slices, multiband factor=5, 4mm slick thickness, FA=90, 64x64 resolution, FOV=192x912, TR/TE=3.5s/19ms, labeling time=1.5s and postlabeling delay=1.7s. Anhedonia was measured using the Mood and Anxiety Symptom Questionnaire Anhedonic Depression Scale (MASQ-ADS), with the Snaith–Hamilton Pleasure Scale (SHAPS) as a secondary measure. Anxiety was measured using the MASQ General Distress Anxious Symptoms Scale. Anhedonia, anxiety and group were included in the regression model. Results: Anhedonia (MASQ-ADS) was associated with increased CBF in the midbrain (T=5.24, p_FWE=0.033), proximal to putative locations of the dorsal/median raphe nuclei (-12, -34, -26). Similar, although weaker, findings were observed with the SHAPS. Conclusion: Anhedonia is associated with altered CBF in the midbrain in a young adult population showing heterogeneous symptoms of distress. Significance: ASL may provide a particularly promising tool to examine enhanced local perfusion, potentially reflecting underlying midbrain serotonergic activity, which is predicted on the basis of LH studies in rodents but has thus far been difficult to investigate in humans

Neuroticism And Individual Differences In Neural Function In Unmedicated Major Depression: Findings From The Embarc Study

BACKGROUND: Personality dysfunction represents one of the only predictors of differential response between active treatments for depression to have replicated. We examine whether depressed patients with higher neuroticism scores, a marker of personality dysfunction, show differences compared with depressed patients with lower scores in the functioning of two brain regions associated with treatment response, the anterior cingulate and anterior insula cortices. METHODS: Functional magnetic resonance imaging data during an emotional Stroop task were collected from 135 adults with major depressive disorder at four academic medical centers participating in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care) study. Secondary analyses were conducted including a sample of 28 healthy subjects. RESULTS: In whole-brain analyses, higher neuroticism among adults with depression was associated with increased activity in and connectivity with the right anterior insula cortex to incongruent compared with congruent emotional stimuli (all k $ 281, all p , .05 familywise error corrected), covarying for concurrent psychiatric distress. We also observed an unanticipated relationship between neuroticism and reduced activity in the precuneus (k 5 269, p , .05 familywise error corrected). Exploratory analyses including healthy subjects suggested that associations between neuroticism and brain function may be nonlinear over the full range of neuroticism scores. CONCLUSIONS: This study provides convergent evidence for the importance of the right anterior insula cortex as a brain-based marker of clinically meaningful individual differences in neuroticism among adults with depression. This is a critical next step in linking personality dysfunction, a replicated clinical predictor of differential antidepressant treatment response, with differences in underlying brain function

Inter-regional connectivity within the win/loss anticipation network in depressed individuals with bipolar disorder, in depressed individuals with major depressive disorder and healthy controls

Identifying biomarkers distinguishing depressed individuals with bipolar disorder (BDD) from those with major depressive disorder (MDD) would help to develop better therapeutic strategies and improve treatment outcomes. Depressed individuals are often biased (i.e., pessimistic bias) in their anticipation of future negative outcomes. Goal: to determine the differences in connectivity within the reward anticipation network between BDD, MDD and HC (healthy controls) using a graph modelling method. BDD had denser connectivity among fronto-striatal regions, while MDD had denser connectivity among occipital regions. BDD and MDD had similar fronto-striatal connectivity that was less dense compared to HC. Altered fronto-striatal and occipital connectivity patterns during win anticipation distinguished BDD from MDD and HC and might reflect a neurobiological mechanism for impaired processing of positive stimuli in BDD

Early infant prefrontal gray matter volume is associated with concurrent and future infant emotionality

Abstract High levels of infant negative emotionality (NE) are associated with emotional and behavioral problems later in childhood. Identifying neural markers of high NE as well as low positive emotionality (PE) in infancy can provide neural markers to aid early identification of vulnerability, and inform interventions to help delay or even prevent psychiatric disorders before the manifestation of symptoms. Prefrontal cortical (PFC) subregions support the regulation of NE and PE, with each PFC subregion differentially specializing in distinct emotional regulation processes. Gray matter (GM) volume measures show good test-retest reliability, and thus have potential use as neural markers of NE and PE. Yet, while studies showed PFC GM structural abnormalities in adolescents and young adults with affective disorders, few studies examined how PFC subregional GM measures are associated with NE and PE in infancy. We aimed to identify relationships among GM in prefrontal cortical subregions at 3 months and caregiver report of infant NE and PE, covarying for infant age and gender and caregiver sociodemographic and clinical variables, in two independent samples at 3 months (Primary: n = 75; Replication sample: n = 40) and at 9 months (Primary: n = 44; Replication sample: n = 40). In the primary sample, greater 3-month medial superior frontal cortical volume was associated with higher infant 3-month NE (p < 0.05); greater 3-month ventrolateral prefrontal cortical volume predicted lower infant 9-month PE (p < 0.05), even after controlling for 3-month NE and PE. GM volume in other PFC subregions also predicted infant 3- and 9-month NE and PE, together with infant demographic factors, caregiver age, and/or caregiver affective instability and anxiety. These findings were replicated in the independent sample. To our knowledge, this is the first study to determine in primary and replication samples associations among infant PFC GM volumes and concurrent and prospective NE and PE, and identify promising, early markers of future psychopathology risk

Resting State Functional Connectivity between Dorsal Attentional Network and Right Inferior Frontal Gyrus in Concussed and Control Adolescents

Concussion among adolescents continues to be a public health concern. Yet, the differences in brain function between adolescents with a recent concussion and adolescents with no history of concussion are not well understood. Although resting state functional magnetic resonance imaging (fMRI) can be a useful tool in examining these differences, few studies have used this technique to examine concussion in adolescents. Here, we investigate the differences in the resting state functional connectivity of 52 adolescents, 38 with a concussion in the previous 10 days (mean age = 15.6; female = 36.8%), and 14 controls with no concussion history (mean age = 15.1; female = 57.1%). Independent component analysis and dual regression revealed that control adolescents had significantly greater functional connectivity between the dorsal attention network (DAN) and right inferior frontal gyrus (RIFG) compared to concussed adolescents (p-corrected < 0.001). Specifically, there was a positive DAN-RIFG connectivity in control, but not concussed, adolescents. Our findings indicate that concussion is associated with disrupted DAN-RIFG connectivity, which may reflect a general, nonspecific response to injury

Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study.

Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE). We also examined bilateral visual cortex activation coupled to outcome anticipation. Significant VS PE-related activity was observed at the first testing session, but at the second testing session, VS PE-related activation was significantly reduced. Conversely, significant VS RE-related activity was observed at time 2 but not time 1. Increases in VS RE-related activity from time 1 to time 2 were significantly associated with decreases in VS PE-related activity from time 1 to time 2 across participants. Intraclass correlations (ICCs) in VS were very low. By contrast, visual cortex activation had much larger ICCs, particularly in individuals with high quality data. Dynamic changes in brain activation are widely predicted, and failure to account for these changes could lead to inaccurate evaluations of the reliability of functional MRI signals. Conventional measures of reliability cannot distinguish between changes specified by algorithmic models of neural function and noisy signal. Here, we provide evidence for the former possibility: reward-related VS activations follow the pattern predicted by temporal difference models of reward learning but have low ICCs

Moderation Of The Relationship Between Reward Expectancy And Prediction Error-related Ventral Striatal Reactivity By Anhedonia In Unmedicated Major Depressive Disorder: Findings From The Embarc Study

Objective—Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error-(discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures