Liam Mason

I Want It Now! Neural Correlates of Hypersensitivity to Immediate Reward in Hypomania

BACKGROUND Hypomania is associated with impulsive decision making and risk taking, characteristics that may arise from hypersensitivity to reward. To date, the neural dynamics underlying intertemporal reward processing have neither been characterized clinically nor in the general population. Taking vulnerability to hypomania as a surrogate model of impulsivity, we utilized event-related potentials to study the neural mechanisms of delay discounting. METHODS In the first experiment, 32 participants completed an established Two Choice Impulsivity Paradigm in which free choice between immediate and delayed rewards was used to quantify impulsivity behaviorally. In the second experiment, electroencephalography was recorded while 32 separately recruited participants completed a speeded response task involving gains and losses of monetary incentives to be paid at three different delays after the experiment. RESULTS In the first experiment, the hypomania-prone group made significantly more immediate choices than the control group. In the second experiment, the hypomania-prone group evidenced greater differentiation between delayed and immediate outcomes in early attention-sensitive (N1) and later reward-sensitive (feedback-related negativity) components. Proneness to hypomania was also associated with greater N1 amplitude to rewards per se. CONCLUSIONS These results indicate steeper delay discounting in hypomania at multiple stages of information processing. The N1 modulation by valence and delay suggests an attentional bias to immediate rewards, which may drive subsequent cognitive appraisal of outcomes (feedback-related negativity). These results highlight the early influence of attention on reward processing and provide support for reward dysregulation accounts of bipolar disorder. Potential implications for mindfulness training and other therapeutic interventions are highlighted.

fMRI evidence of a relationship between hypomania and both increased goal-sensitivity and positive outcome-expectancy bias.

BACKGROUND Mania is argued to stem from the dysfunctional processing of reward. Investigation of hypomania in healthy samples has the potential to offer refined insight into the particular aspects of reward processing in mania that are dysfunctional. METHOD In this study, fMRI was employed in contrasting a sample of 12 unmedicated subclinical hypomanic individuals with a sample of 12 unmedicated controls in order to investigate reward-related processing in a reinforcement-learning task. RESULTS Four findings in the hypomania-prone group relative to the control group supported atypical reward processing. Firstly, striatal activation that correlated with reward value and prediction error was stronger in response to cues and outcomes respectively, consistent with hypomania being related to an enhanced perception of the value of goals that may lead to reward. Secondly, value-related medial temporal activation was stronger in response to cues, suggesting that in hypomania-prone individuals, stimuli in memory were represented in accordance with their perceived value. Thirdly, these effects failed to be modulated by the actual value of outcomes, suggesting that hypomania is related to a decreased ability to discriminate between cues differing in value. Fourthly, increased insula activation in response to expected, but absent, reward was consistent with a bias towards expecting positive outcomes in decision-making. CONCLUSION Together, the findings suggest that enhanced perception and representation of goal-value that nonetheless fails to discriminate on the basis of actual goal-value, coupled with a positive outcome-expectancy bias, could be causally related to insatiable and indiscriminate reward seeking in mania.

Decision-making and trait impulsivity in bipolar disorder are associated with reduced prefrontal regulation of striatal reward valuation.

Bipolar disorder is characterized by impaired decision-making captured in impulsivity and risk-taking. We sought to determine whether this is driven by a failure to effectively weight the lower-order goal of obtaining a strongly desired reward in relation to higher-order goals, and how this relates to trait impulsivity and risk-taking. We hypothesized that in bipolar disorder the weighting of valuation signals converging on ventromedial prefrontal cortex are more heavily weighted towards ventral striatum inputs (lower-order), with less weighting of dorsolateral prefrontal cortex inputs (higher-order). Twenty euthymic patients with bipolar disorder not in receipt of antipsychotic medication and 20 case-matched controls performed a roulette task during functional magnetic resonance imaging. Activity in response to high-probability (‘safe’) and low-probability (‘risky’) prospects was measured during both anticipation, and outcome. In control subjects, anticipatory and outcome-locked activity in dorsolateral prefrontal cortex was greater for safe than risky reward prospects. The bipolar disorder group showed the opposite pattern with preferential response to risky rewards. This group also showed increased anticipatory and outcome-locked activity in ventral striatum in response to rewards. In control subjects, however, ventromedial prefrontal activation was positively associated with both ventral striatum and dorsolateral prefrontal activity; patients evidenced a strong positive association with ventral striatum, but a negative association with dorsolateral prefrontal cortex. Response to high-probability rewards in dorsolateral prefrontal cortex was inversely associated with trait impulsivity and risk-taking in the bipolar disorder group. Our findings suggest that clinically impulsive and risky decision-making are related to subjective valuation that is biased towards lower-order preference, with diminished integration of higher-order goals. The findings extend a functional neuroanatomical account of disorders characterized by clinically impulsive decision-making, and provide targets for evaluating interventions that foster self-control.

Better than I thought: positive evaluation bias in hypomania.

Background Mania is characterised by increased impulsivity and risk-taking, and psychological accounts argue that these features may be due to hypersensitivity to reward. The neurobiological mechanisms remain poorly understood. Here we examine reinforcement learning and sensitivity to both reward and punishment outcomes in hypomania-prone individuals not receiving pharmacotherapy. Method We recorded EEG from 45 healthy individuals split into three groups by low, intermediate and high self-reported hypomanic traits. Participants played a computerised card game in which they learned the reward contingencies of three cues. Neural responses to monetary gain and loss were measured using the feedback-related negativity (FRN), a component implicated in motivational outcome evaluation and reinforcement learning. Results As predicted, rewards elicited a smaller FRN in the hypomania-prone group relative to the low hypomania group, indicative of greater reward responsiveness. The hypomania-prone group also showed smaller FRN to losses, indicating diminished response to negative feedback. Conclusion Our findings indicate that proneness to hypomania is associated with both reward hypersensitivity and discounting of punishment. This positive evaluation bias may be driven by aberrant reinforcement learning signals, which fail to update future expectations. This provides a possible neural mechanism explaining risk-taking and impaired reinforcement learning in BD. Further research will be needed to explore the potential value of the FRN as a biological vulnerability marker for mania and pathological risk-taking.

Delay discounting as emotional processing: An electrophysiological study

Both theoretical models and functional imaging studies implicate the involvement of emotions within the delay discounting process. However, defining this role has been difficult to establish with neuroimaging techniques given the automaticity of emotional responses. To address this, the current study examined electrophysiological correlates involved in the detection and evaluation of immediate and delayed monetary outcomes. Our results showed that modulation of both early and later ERP components previously associated with affective stimuli processing are sensitive to the signalling of delayed rewards. Together with behavioural reaction times that favoured immediacy, we demonstrated, for the first time, that time delays modify the incentive value of monetary rewards via mechanisms of emotional bias and selective visual attention. Furthermore, our data are consistent with the hypothesis that delayed and thus intangible rewards are perceived less saliently, and rely on emotion as a common currency within decision making. This study provides a new approach to delay discounting and highlights a potential novel route through which delay discounting may be investigated.

Cognitive Behavioral Therapy Normalizes Functional Connectivity for Social Threat in Psychosis

Psychosis is often characterized by paranoia and poor social functioning. Neurally, there is evidence of functional dysconnectivity including abnormalities when processing facial affect. We sought to establish whether these abnormalities are resolved by cognitive behavioral therapy for psychosis (CBTp). The study involved 38 outpatients with one or more persistent positive psychotic symptoms, and 20 healthy participants. All participants completed an implicit facial affect processing task during functional magnetic resonance imaging (fMRI). Subsequently, patients either continued to receive standard care only (SCO, n = 16) or received CBTp on top of standard care (+CBTp, n = 22), with fMRI repeated 6–8 months later. To examine the mechanisms underlying CBTp-led changes in threat processing and appraisal, functional connectivity during the social threat (angry faces) condition was assessed separately from left amygdala and right dorsolateral prefrontal cortex (DLPFC) seeds. At baseline, patients, compared with healthy participants, showed greater amygdala connectivity with the insula and visual areas, but less connectivity with somatosensory areas. These differences normalized following CBTp and, compared with the SCO group, the +CBTp group showed greater increases in amygdala connectivity with DLPFC and inferior parietal lobule, with the latter correlating with improvement in positive symptoms. From the DLPFC seed, the +CBTp (compared with SCO) group showed significantly greater increase in DLPFC connectivity with other prefrontal regions including dorsal anterior cingulate and ventromedial prefrontal cortex. These findings indicate that CBTp strengthens connectivity between higher-order cognitive systems and those involved in threat and salience, potentially facilitating reappraisal.

Functional connectivity predictors and mechanisms of cognitive behavioural therapies: A systematic review with recommendations.

Objective: While there is now strong evidence that psychological therapies can alter the activity of individual brain regions, their impact on the functional integration between regions has not yet been systematically evaluated. This area is important given that brain dysconnectivity has been implicated across almost all psychiatric disorders. Accordingly, we sought to establish connectivity predictors and mechanisms of effective psychological therapies. We further establish whether connectivity changes represent normalisation of disorder pathophysiology or compensatory changes. Method: We reviewed studies examining structural and functional connectivity longitudinally as either a predictor or outcome variable of successful psychological therapies across psychiatric disorders. Results: Fifteen studies met our inclusion criteria. All but three related to cognitive behavioural therapy. Of these, five assessed resting state, nine probed affective processing and one probed cognitive processing. Twelve studies reported evidence of functional connectivity as a significant predictor or outcome of cognitive behavioural therapy, with prefronto-limbic circuitry most commonly implicated. Only six studies included healthy participants, limiting direct inferences about normalisation as opposed to compensatory changes. Anxiety disorders were overrepresented, totalling 13 of the studies reviewed. No studies examined structural connectivity or utilised analyses allowing the directionality of functional connectivity to be inferred. Conclusion: While the evidence base is still in its infancy for other therapy approaches, there was clearer evidence that functional connectivity both predicts and is altered by cognitive behavioural therapy. Connections from prefrontal cortex appear especially key, perhaps given their role in cognitive appraisal of lower order affective, motivational and cognitive processes. A number of recommendations are made for this rapidly developing literature.

Attentional Bias Predicts Increased Reward Salience and Risk Taking in Bipolar Disorder.

BACKGROUND There is amassing evidence that risky decision-making in bipolar disorder is related to reward-based differences in frontostriatal regions. However, the roles of early attentional and later cognitive processes remain unclear, limiting theoretical understanding and development of targeted interventions. METHODS Twenty euthymic bipolar disorder and 19 matched control participants played a Roulette task in which they won and lost money. Event-related potentials and source analysis were used to quantify predominantly sensory-attentional (N1), motivational salience (feedback-related negativities [FRN]), and cognitive appraisal (P300) stages of processing. We predicted that the bipolar disorder group would show increased N1, consistent with increased attentional orienting, and reduced FRN, consistent with a bias to perceive outcomes more favorably. RESULTS As predicted, the bipolar disorder group showed increased N1 and reduced FRN but no differences in P300. N1 amplitude was additionally associated with real-life risk taking, and N1 source activity was reduced in visual cortex but increased activity in precuneus, frontopolar, and premotor cortex, compared to those of controls. CONCLUSIONS These findings demonstrate an early attentional bias to reward that potentially drives risk taking by priming approach behavior and elevating reward salience in the frontostriatal pathway. Although later cognitive appraisals of these inputs may be relatively intact in remission, interventions targeting attention orienting may also be effective in long-term reduction of relapse.

My Therapist is a Student? The Impact of Therapist Experience and Client Severity on Cognitive Behavioural Therapy Outcomes for People with Anxiety Disorders

BACKGROUND Allocation of trainee therapist cases is often performed based on intuition and clinical circumstances, with lack of empirical evidence on the role of severity of presenting problem. This has the potential to be anxiety-provoking for supervisors, trainees and service users themselves. AIMS To determine how therapist experience interacts with symptom severity in predicting client outcomes. METHOD An intention-to-treat analysis of annual outcome data for primary and secondary care clients seen by a specialist anxiety disorders service. 196 clients were stratified into mild, moderate and baseline severe symptoms of anxiety (GAD-7) and depression (PHQ-9). We measured percentage change on these measures, as well as number of sessions and therapy dropout. We also examined rates of reliable and clinically significant change on disorder-specific measures. We hypothesized that qualified therapists would achieve better outcomes than trainees, particularly for severe presentations. RESULTS Overall, outcomes were comparable between trainee and qualified therapists on all measures, and trainees additionally utilized fewer therapy sessions. There was however an interaction between anxiety severity (GAD-7) and therapist group, such that severely anxious clients achieved greater symptom improvement with qualified as compared to trainee therapists. Further, for trainee but not qualified therapists, baseline anxiety was negatively associated with rate of reliable and clinically significant change on disorder-specific measures. CONCLUSIONS These findings indicate generally favourable outcomes for trainee therapists delivering manualized treatments for anxiety disorders. They additionally suggest that trainee therapists may benefit from additional support when working with clients that present with severe anxiety.

Brain connectivity changes occurring following cognitive behavioural therapy for psychosis predict long-term recovery

Little is known about the psychobiological mechanisms of cognitive behavioural therapy for psychosis (CBTp) and which specific processes are key in predicting favourable long-term outcomes. Following theoretical models of psychosis, this proof-of-concept study investigated whether the long-term recovery path of CBTp completers can be predicted by the neural changes in threat-based social affective processing that occur during CBTp. We followed up 22 participants who had undergone a social affective processing task during functional magnetic resonance imaging along with self-report and clinician-administered symptom measures, before and after receiving CBTp. Monthly ratings of psychotic and affective symptoms were obtained retrospectively across 8 years since receiving CBTp, plus self-reported recovery at final follow-up. We investigated whether these long-term outcomes were predicted by CBTp-led changes in functional connections with dorsal prefrontal cortical and amygdala during the processing of threatening and prosocial facial affect. Although long-term psychotic symptoms were predicted by changes in prefrontal connections during prosocial facial affective processing, long-term affective symptoms were predicted by threat-related amygdalo-inferior parietal lobule connectivity. Greater increases in dorsolateral prefrontal cortex connectivity with amygdala following CBTp also predicted higher subjective ratings of recovery at long-term follow-up. These findings show that reorganisation occurring at the neural level following psychological therapy can predict the subsequent recovery path of people with psychosis across 8 years. This novel methodology shows promise for further studies with larger sample size, which are needed to better examine the sensitivity of psychobiological processes, in comparison to existing clinical measures, in predicting long-term outcomes.