Ryan Smith

Antidepressant effects of sertraline associated with volume increases in dorsolateral prefrontal cortex

BACKGROUND Structural brain imaging has revealed differences in gray matter volume between depressed individuals and control subjects in key structures related to emotion. The aim of the present study was to assess within subjects whether regional changes in gray matter volume were observed over time in depressed patients treated with sertraline. METHODS Thirteen depressed patients were assigned to selective serotonin reuptake inhibitor (SSRI) treatment with sertraline. Structural magnetic resonance imaging (MRI) was performed at four time points over 12 weeks of treatment. Depressed individuals were compared to a control group of 10 subjects scanned at the same time points using voxel based morphometry and a statistical growth modeling technique. RESULTS SSRI-treated patients showed a region of significantly increasing gray matter volume over time within the left dorsolateral prefrontal cortex (DLPFC) that specifically correlated with decreases in self-reported depression levels. No statistically significant changes were observed related to time in controls. LIMITATIONS This study included a small sample size and the method of analysis was capable of detecting only linear changes in volume. CONCLUSIONS Effective antidepressant treatment with sertraline is associated with left DLPFC volume increases. These volume increases may reflect cortical architectural changes associated with top-down neuronal modulation of emotion.

The neural basis of one's own conscious and unconscious emotional states

The study of emotional states has recently received considerable attention within the cognitive and neural sciences. However, limited work has been done to synthesize this growing body of literature within a coherent hierarchical, neuro-cognitive framework. In this article, we review evidence pertaining to three interacting hierarchical neural systems associated with the generation, perception and regulation of ones own emotional state. In the framework we propose, emotion generation proceeds through a series of appraisal mechanisms - some of which appear to require more cognitively sophisticated computational processing (and hence more time) than others - that ultimately trigger iterative adjustments to ones bodily state (as well as to the modes of processing in other cognitive systems). Perceiving ones own emotions then involves a multi-stage interoceptive/somatosensory process by which these body state patterns are detected and assigned conceptual emotional meaning. Finally, emotion regulation can be understood as a hierarchical control system that, at various levels, modulates autonomic reactions, appraisal mechanisms, attention, the contents of working memory, and goal-directed action selection. We highlight implications this integrative model may have for competing theories of emotion and emotional consciousness and for guiding future research.

Subgenual anterior cingulate cortex activity covariation with cardiac vagal control is altered in depression

BACKGROUND We tested the hypothesis that subgenual anterior cingulate cortex (sgACC) participates in concurrently regulating shifts in both affective state and cardiac vagal control. METHODS Eleven healthy adults and 8 depressed subjects performed the Emotional Counting Stroop task in alternating 15-second blocks of emotion words and neutral words while undergoing functional magnetic resonance imaging (fMRI) and electrocardiography (ECG). We measured the absolute value of change between adjacent 15-second blocks in both cardiac vagal control and the BOLD signal in specific regions of interest. RESULTS Strong positive correlations were observed in healthy control participants between changes in cardiac vagal control and changes in BOLD signal intensity in sgACC (BA25) (right: r=.67, p<.02; left r=.69, p<.02), as well as other key structures in the medial visceromotor network. Depressed subjects showed no significant correlations between cardiac vagal control and BOLD signal intensity within BA25 or any other brain region examined. During the transition from depression-specific emotion blocks to neutral blocks, the correlation between BOLD signal change in BA25 and cardiac vagal control change was significantly greater in controls than in depressed subjects (p<.04). CONCLUSIONS Findings in healthy volunteers suggest that sgACC participates in affective state shifting. The latter function appears to be altered in depressed individuals, and may have implications for the unvarying mood and vagal dysfunction associated with depression. LIMITATIONS Limitations include a small sample size, an inability to disentangle afferent versus efferent contributions to the results, and the lack of a whole-brain analysis.

Altered functional connectivity between medial prefrontal cortex and the inferior brainstem in major depression during appraisal of subjective emotional responses: A preliminary study

OBJECTIVE We tested the hypothesis that reduced rostral anterior cingulate cortex (rACC)-subcortical functional connectivity in depressed subjects might account for depression-related autonomic dysregulation. METHODS Ten healthy and ten depressed subjects categorized their immediate subjective emotional responses to picture sets while undergoing functional magnetic resonance imaging and electrocardiography. Using an rACC cluster commonly activated in both groups by emotion categorization as a seed region, we then performed voxel-wise functional connectivity analyses to examine rACC connectivity across the brain in depressed and control subjects. RESULTS rACC had significantly stronger connectivity with a region of the inferior pons in controls than in depressed subjects. Within-subjects differences in rACC-pons connectivity also significantly correlated with measures of both heart rate variability and depression severity. CONCLUSIONS These findings support the hypothesis that autonomic dysregulation in depression may be associated with a functional disconnection between rACC and autonomic brainstem nuclei.

Reconciling cognitive and affective neuroscience perspectives on the brain basis of emotional experience.

HighlightsAffective Neuroscience (AN) involves more invasive approaches in animals.Cognitive Neuroscience (CN) involves less invasive approaches to emotion in humans.AN and CN often promote discordant views on the neural basis of emotional experience.AN, unlike CN, holds that subcortical processes alone are sufficient for conscious emotion.Future experiments we describe may be required to integrate these perspectives. ABSTRACT The “affective” and “cognitive” neuroscience approaches to understanding emotion (AN and CN, respectively) represent potentially synergistic, but as yet unreconciled, theoretical perspectives, which may in part stem from the methods that these distinct perspectives routinely employ—one focusing on animal brain emotional systems (AN) and one on diverse human experimental approaches (CN). Here we present an exchange in which each approach (1) describes its own theoretical perspective, (2) offers a critique of the other perspective, and then (3) responds to each others critique. We end with a summary of points of agreement and disagreement, and describe possible future experiments that could help resolve the remaining controversies. Future work should (i) further characterize the structure/function of subcortical circuitry with respect to its role in generating emotion, and (ii) further investigate whether sub‐neocortical activations alone are sufficient (as opposed to merely necessary) for affective experiences, or whether subsequent cortical representation of an emotional response is also required.

Unconscious emotion: A cognitive neuroscientific perspective

While psychiatry and clinical psychology have long discussed the topic of unconscious emotion, and its potentially explanatory role in psychopathology, this topic has only recently begun to receive attention within cognitive neuroscience. In contrast, neuroscientific research on conscious vs. unconscious processes within perception, memory, decision-making, and cognitive control has seen considerable advances in the last two decades. In this article, we extrapolate from this work, as well as from recent neural models of emotion processing, to outline multiple plausible neuro-cognitive mechanisms that may be able to explain why various aspects of ones own emotional reactions can remain unconscious in specific circumstances. While some of these mechanisms involve top-down or motivated factors, others instead arise due to bottom-up processing deficits. Finally, we discuss potential implications that these different mechanisms may have for therapeutic intervention, as well as how they might be tested in future research.

Role of medial prefrontal cortex in representing one’s own subjective emotional responses: A preliminary study

The medial prefrontal cortex (mPFC) has been implicated in attending to ones own emotional states, but the role of emotional valence in this context is not understood. We examined valence-specific BOLD activity in a previously validated functional magnetic resonance imaging (fMRI) paradigm. Ten healthy subjects viewed emotional pictures and categorized their experience as pleasant, unpleasant or neutral. All three categories activated a common region within mPFC. Subtraction of neutral from pleasant or unpleasant conditions instead revealed ventromedial PFC (vmPFC), suggesting that this region represents emotional valence. During exteroceptive attention, greater mPFC responses were observed in response to emotional relative to neutral stimuli, consistent with studies implicating mPFC in the top-down modulation of emotion-biased attention. These findings may help to integrate the two proposed roles of mPFC in emotional representation and top-down modulation of subcortical structures.

Increased association over time between regional frontal lobe BOLD change magnitude and cardiac vagal control with sertraline treatment for major depression.

Regions of the medial visceromotor network (MVN) participate in concurrently regulating shifts in both affective state and cardiac vagal control in the attentional background, and this regulatory ability may be impaired in depression. We examined whether the relationship between changes in BOLD within MVN regions and changes in cardiac vagal control (VC) during affective state shifting changed with depression treatment. Ten depressed and ten control subjects performed an emotional counting Stroop task designed to trigger affective change in the attentional background while undergoing functional magnetic resonance imaging and concurrent electrocardiography (ECG) on four occasions: week 0 (pre-treatment) and weeks 2, 6 and 12 of treatment on sertraline. We measured the absolute value of change between adjacent emotional and neutral conditions in both VC and the BOLD signal in specific regions of the MVN. Over time consistent increases were observed in BOLD-VC magnitude correlations in depressed subjects in subgenual ACC and left DLPFC, which strongly correlated with depressive symptom improvement. Symptom improvement over time was also associated with decreases in the magnitude of both BOLD shifts and VC shifts within-subjects. This suggests that as depressive symptoms improve on sertraline, subgenual ACC and DLPFC may more efficiently regulate visceral states during affective state shifting.

Maintaining the feelings of others in working memory is associated with activation of the left anterior insula and left frontal-parietal control network

Abstract The maintenance of social/emotional information in working memory (SWM/EWM) has recently been the topic of multiple neuroimaging studies. However, some studies find that SWM/EWM involves a medial frontal-parietal network while others instead find lateral frontal-parietal activations similar to studies of verbal and visuospatial WM. In this study, we asked 26 healthy volunteers to complete an EWM task designed to examine whether different cognitive strategies— maintaining emotional images, words, or feelings— might account for these discrepant results. We also examined whether differences in EWM performance were related to general intelligence (IQ), emotional intelligence (EI), and emotional awareness (EA). We found that maintaining emotional feelings, even when accounting for neural activation attributable to maintaining emotional images/words, still activated a left lateral frontal-parietal network (including the anterior insula and posterior dorsomedial frontal cortex). We also found that individual differences in the ability to maintain feelings were positively associated with IQ and EA, but not with EI. These results suggest that maintaining the feelings of others (at least when perceived exteroceptively) involves similar frontal-parietal control networks to exteroceptive WM, and that it is similarly linked to IQ, but that it also may be an important component of EA.

The structure of emotional experience and its relation to trait emotional awareness: A theoretical review.

Emotional experience (EE) and trait emotional awareness (tEA) have recently become topics of considerable experimental/theoretical interest within the cognitive and neural sciences. However, to date there has been limited empirical focus on how individual differences in the factors contributing to EE (a state-based construct) might account for differences in tEA. To promote clear, well-guided empirical research in this area, in this article we first offer a concise review of the primary factors contributing to EE. We then provide a theoretical investigation into how individual differences in these factors (i.e., differences in affective response generation, affective response representation, and conscious access) could mechanistically account for differences in tEA; we also discuss plausible origins of these individual differences in light of current empirical findings. Finally, we outline possible experiments that would support (or fail to support) the role of each factor in explaining differences in tEA—and how this added knowledge could shed light on the known link between low tEA and multiple emotion-related mental and systemic medical disorders.