Biology subjects

Harmer, C.

Publications and source records attributed to Harmer, C..

4 recordsLinked to original sources

bioRxiv2018

Exploring the prediction of emotional valence and pharmacologic effect across fMRI studies of antidepressants.

BackgroundClinically approved antidepressants modulate the brains emotional valence circuits, suggesting that the response of these circuits could serve as a biomarker for screening candidate antidepressant drugs. However, it is necessary that these modulations can be reliably detected. Here, we apply a cross-validated predictive model to classify emotional valence and pharmacologic effect across eleven task-based fMRI datasets (n=306) exploring the effect of antidepressant administration on emotional face processing.\n\nMethodsWe created subject-level contrast of parameter estimates of the emotional faces task and used the Shen whole-brain parcellation scheme to define 268 subject-level features that trained a cross-validated gradient-boosting machine protocol to classify emotional valence (fearful vs happy face visual conditions) and pharmacologic effect (drug vs placebo administration) within and across studies.\n\nResultsWe found patterns of brain activity that classify emotional valence with a statistically significant level of accuracy (70% across-all-subjects; range from 50-87% across-study). Our classifier failed to consistently discriminate drug from placebo. Subject population (healthy or unhealthy), treatment group (drug or placebo), and drug administration protocol (dose and duration) affected this accuracy with similar populations better predicting one another.\n\nConclusionsWe found limited evidence that antidepressants modulated brain response in a consistent manner, however found a consistent signature for emotional valence. Variable functional patterns across studies suggest that predictive modeling can inform biomarker development in mental health and in pharmacotherapy development. Our results suggest that case-controlled designs and more standardized protocols are required for functional imaging to provide robust biomarkers for drug development.

neuroscience↗

bioRxiv2018

Emotional recognition training modifies neural response to emotional faces but does not improve mood in healthy volunteers with high levels of depressive symptoms

IMPORTANCEDepression is a debilitating and highly prevalent mental health disorder. There is a need for new, effective, and scalable treatments for depression, and cognitive bias modification (CBM) of negative emotional processing biases has been suggested as one possibility. Such treatments may form the basis of digital therapeutics, that could be administered remotely and at low cost, should they prove to be effective.\n\nOBJECTIVESStudy one was designed to determine neural correlates of a recently developed CBM technique for emotion recognition training; specifically, our aim was to compare the effects of training vs placebo on pre-specified regions of interest involved in emotion processing that are known to be sensitive to antidepressant treatment. Study two aimed to investigate efficacy of training on mood measures at 2 and 6-week follow-up and was powered to replicate and extend earlier findings.\n\nDESIGN, SETTING, AND PARTICIPANTSBoth studies were double blind RCTs, in which participants completed five sessions of emotion recognition training or sham training, in the laboratory, over a one-week period. In study one (N=37), following this training, participants completed a novel emotion recognition task whilst undergoing fMRI. In study two (N=190), measures of mood were assessed post training, and at 2-week and 6-week follow-up. Both studies recruited analogue samples of healthy volunteers with high levels of depressive symptoms (BDI-ii > 14).\n\nMAIN OUTCOMES AND MEASURESIn study one, our primary outcome was neural activation in the following pre-specified regions of interest: the bilateral amygdala, the mPFC, bilateral dlPFC, and the occipital cortex. In study two, our primary outcome was depressive symptoms over the last 2 weeks assessed using the BDI-ii at 6-week follow-up. Secondary outcomes included depressive symptoms measured using the HAM-D, and positive and negative affect assessed using the PANAS.\n\nRESULTSIn both studies, CBM resulted in a change in emotion recognition bias, which (in study two) persisted for 6 weeks after the end of the CBM phase. In study one, CBM resulted in increases neural activation to happy faces compared to sad faces, with this effect driven by an increase in neural activity for happy faces. We saw this increase in activation for this contrast at both the whole brain level and among our a priori ROIs, specifically the mPFC and bilateral amygdala. In study two, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias.\n\nCONCLUSIONS AND RELEVANCECBM of emotion recognition appears to have effects on neural activity that are similar in some respects to those induced by SSRI administration (study one), but we find no evidence that this has any effect on self-reported mood in an analogue sample of healthy volunteers with low mood (study two).

neuroscience↗

bioRxiv2018

Attentional Bias Modification Alters fMRI Response towards Negative Stimuli in Residual Depression

BackgroundModification of attentional biases (ABM) may lead to more adaptive emotion perception and emotion regulation. Understanding the neural basis of these effects may lead to greater precision for future treatment development. Task-related fMRI following ABM training has so far not been investigated in depression. The main aim of the RCT was to explore differences in brain activity after ABM training in response to emotional stimuli.\n\nMethodsA total of 134 previously depressed individuals were randomized into 14 days of ABM- or a placebo training followed by an fMRI emotion regulation task. Depression symptoms and subjective ratings of perceived negativity during fMRI was examined between the training groups. Brain activation was explored within predefined areas (SVC) and across the whole brain. Activation in areas associated with changes in attentional biases (AB) and degree of depression was explored.\n\nResultsThe ABM group showed reduced activation within the amygdala and within the anterior cingulate cortex (ACC) when passively viewing negative images compared to the placebo group. No group differences were found within predefined SVCs associated with emotion regulation strategies. Response within the temporal cortices was associated with degree of change in AB and with degree of depressive symptoms in ABM versus placebo.\n\nLimitationsThe findings should be replicated in other samples of depressed patients and in studies using designs that allow analyses of within-group variability from baseline to follow-up.\n\nConclusionsABM training has an effect on brain function within circuitry associated with emotional appraisal and the generation of affective states.\n\nClinicaltrials.gov identifier: NCT02931487

clinical trials↗

bioRxiv2017

Prefrontal cortex regulates amygdala response to threat in trait anxiety

BackgroundHighly co-morbid mood and anxiety disorders are associated with aberrant fronto-limbic signalling during emotional processing. Animal models suggest that hypoactive prefrontal cortex weakens top-down control of limbic structures, causing heightened limbic and behavioural reactivity to negative information. Here we tested for this causal mechanism in human trait anxiety. We reasoned that if dorsolateral prefrontal cortex controls amygdala response to affective information, then stimulation of that brain region should reduce the hyperactive amygdala threat responsivity seen in trait anxiety.\n\nMethodsUsing a within-subjects design, sixteen high-trait anxious females received active and sham transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex, in counterbalanced order, with sessions timed to be at least one month apart. Each session was followed immediately by a functional magnetic resonance imaging (fMRI) scan during which participants performed an attentional task with threat-related distractors.\n\nResultsAs predicted, compared to sham stimulation, active prefrontal cortex stimulation reduced amygdala threat reactivity and simultaneously increased activity in cortical regions associated with attentional control and improved task accuracy.\n\nConclusionsThese results demonstrate a causal role for impoverished frontal regulation of amygdaloid function in attentional capture by threat in trait anxiety. The finding that prefrontal stimulation reduces amygdala threat reactivity acutely indicates a neurocognitive mechanism that could contribute to tDCS treatment effects in affective disorders.

neuroscience↗