Frontoamygdalar Effective Connectivity in Youth Depression and Treatment Response.

BACKGROUND: Emotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how these dynamics relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cognitive reappraisal in youths with depression and to test whether pathway dynamics are predictive of individual response to combined cognitive behavioral therapy plus treatment with fluoxetine or placebo. METHODS: One hundred seven young people with moderate to severe depression and 94 healthy control participants completed a functional magnetic resonance imaging cognitive reappraisal task. After the task, 87 participants with depression were randomized and received 12 weeks of cognitive behavioral therapy plus either fluoxetine or placebo. Dynamic causal modeling was used to map frontoamygdalar effective connectivity during reappraisal and to assess the predictive capacity of baseline frontoamygdalar effective connectivity on depression diagnosis and posttreatment depression remission. RESULTS: Young people with depression showed weaker inhibitory modulation of ventrolateral prefrontal cortex to amygdala connectivity during reappraisal (0.29 Hz, posterior probability = 1.00). Leave-one-out cross-validation demonstrated that this effect was sufficiently large to predict individual diagnostic status (r = 0.20, p = .003). Posttreatment depression remission was associated with weaker excitatory ventromedial prefrontal cortex to amygdala connectivity (-0.56 Hz, posterior probability = 1.00) during reappraisal at baseline, though this effect did not predict individual remission status (r = -0.02, p = .561). CONCLUSIONS: Frontoamygdalar effective connectivity shows promise in identifying youth depression diagnosis, and circuits responsible for negative affect regulation are implicated in responsiveness to first-line depression treatments.

The influence of the subcortex and brain stem on overeating: How advances in functional neuroimaging can be applied to expand neurobiological models to beyond the cortex.

Functional neuroimaging has become a widely used tool in obesity and eating disorder research to explore the alterations in neurobiology that underlie overeating and binge eating behaviors. Current and traditional neurobiological models underscore the importance of impairments in brain systems supporting reward, cognitive control, attention, and emotion regulation as primary drivers for overeating. Due to the technical limitations of standard field strength functional magnetic resonance imaging (fMRI) scanners, human neuroimaging research to date has focused largely on cortical and basal ganglia effects on appetitive behaviors. The present review draws on animal and human research to highlight how neural signaling encoding energy regulation, reward-learning, and habit formation converge on hypothalamic, brainstem, thalamic, and striatal regions to contribute to overeating in humans. We also consider the role of regions such as the mediodorsal thalamus, ventral striatum, lateral hypothalamus and locus coeruleus in supporting habit formation, inhibitory control of food craving, and attentional biases. Through these discussions, we present proposals on how the neurobiology underlying these processes could be examined using functional neuroimaging and highlight how ultra-high field 7-Tesla (7 T) fMRI may be leveraged to elucidate the potential functional alterations in subcortical networks. Focus is given to how interactions of these regions with peripheral endocannabinoids and neuropeptides, such as orexin, could be explored. Technical and methodological aspects regarding the use of ultra-high field 7 T fMRI to study eating behaviors are also reviewed.

A thalamo-centric neural signature for restructuring negative self-beliefs.

Negative self-beliefs are a core feature of psychopathology. Despite this, we have a limited understanding of the brain mechanisms by which negative self-beliefs are cognitively restructured. Using a novel paradigm, we had participants use Socratic questioning techniques to restructure negative beliefs during ultra-high resolution 7-Tesla functional magnetic resonance imaging (UHF 7 T fMRI) scanning. Cognitive restructuring elicited prominent activation in a fronto-striato-thalamic circuit, including the mediodorsal thalamus (MD), a group of deep subcortical nuclei believed to synchronize and integrate prefrontal cortex activity, but which has seldom been directly examined with fMRI due to its small size. Increased activity was also identified in the medial prefrontal cortex (MPFC), a region consistently activated by internally focused mental processing, as well as in lateral prefrontal regions associated with regulating emotional reactivity. Using Dynamic Causal Modelling (DCM), evidence was found to support the MD as having a strong excitatory effect on the activity of regions within the broader network mediating cognitive restructuring. Moreover, the degree to which participants modulated MPFC-to-MD effective connectivity during cognitive restructuring predicted their individual tendency to engage in repetitive negative thinking. Our findings represent a major shift from a cortico-centric framework of cognition and provide important mechanistic insights into how the MD facilitates key processes in cognitive interventions for common psychiatric disorders. In addition to relaying integrative information across basal ganglia and the cortex, we propose a multifaceted role for the MD whose broad excitatory pathways act to increase synchrony between cortical regions to sustain complex mental representations, including the self.