Autonomic cardiovascular dysregulation as a potential mechanism underlying depression and coronary artery bypass grafting surgery outcomes.

BACKGROUND: Coronary artery bypass grafting (CABG) is often used to treat patients with significant coronary heart disease (CHD). To date, multiple longitudinal and cross-sectional studies have examined the association between depression and CABG outcomes. Although this relationship is well established, the mechanism underlying this relationship remains unclear. The purpose of this study was twofold. First, we compared three markers of autonomic nervous system (ANS) function in four groups of patients: 1) Patients with coronary heart disease and depression (CHD/Dep), 2) Patients without CHD but with depression (NonCHD/Dep), 3) Patients with CHD but without depression (CHD/NonDep), and 4) Patients without CHD and depression (NonCHD/NonDep). Second, we investigated the impact of depression and autonomic nervous system activity on CABG outcomes. METHODS: Patients were screened to determine whether they met some of the study's inclusion or exclusion criteria. ANS function (i.e., heart rate, heart rate variability, and plasma norepinephrine levels) were measured. Chi-square and one-way analysis of variance were performed to evaluate group differences across demographic, medical variables, and indicators of ANS function. Logistic regression and multiple regression analyses were used to assess impact of depression and autonomic nervous system activity on CABG outcomes. RESULTS: The results of the study provide some support to suggest that depressed patients with CHD have greater ANS dysregulation compared to those with only CHD or depression. Furthermore, independent predictors of in-hospital length of stay and non-routine discharge included having a diagnosis of depression and CHD, elevated heart rate, and low heart rate variability. CONCLUSIONS: The current study presents evidence to support the hypothesis that ANS dysregulation might be one of the underlying mechanisms that links depression to cardiovascular CABG surgery outcomes. Thus, future studies should focus on developing and testing interventions that targets modifying ANS dysregulation, which may lead to improved patient outcomes.

The Representation of Emotion in Autonomic and Central Nervous System Activity

Phenomenologically, humans effectively label and report feeling distinct emotions, yet the extent to which emotions are represented categorically in nervous system activity is controversial. Theoretical accounts differ in this regard, some positing distinct emotional experiences emerge from a dimensional representation (e.g., along axes of valence and arousal) whereas others propose emotions are natural categories, with dedicated neural bases and associated response profiles. This dissertation aims to empirically assess these theoretical accounts by examining how emotions are represented (either as disjoint categories or as points along continuous dimensions) in autonomic and central nervous system activity by integrating psychophysiological recording and functional neuroimaging with machine-learning based analytical methods. Results demonstrate that experientially, emotional events are well-characterized both along dimensional and categorical frameworks. Measures of central and peripheral responding discriminate among emotion categories, but are largely independent of valence and arousal. These findings suggest dimensional and categorical aspects of emotional experience are driven by separable neural substrates and demonstrate that emotional states can be objectively quantified on the basis of nervous system activity.

Advances in understanding mechanisms of thalamic relays in cognition and behavior.

The main impetus for a mini-symposium on corticothalamic interrelationships was the recent number of studies highlighting the role of the thalamus in aspects of cognition beyond sensory processing. The thalamus contributes to a range of basic cognitive behaviors that include learning and memory, inhibitory control, decision-making, and the control of visual orienting responses. Its functions are deeply intertwined with those of the better studied cortex, although the principles governing its coordination with the cortex remain opaque, particularly in higher-level aspects of cognition. How should the thalamus be viewed in the context of the rest of the brain? Although its role extends well beyond relaying of sensory information from the periphery, the main function of many of its subdivisions does appear to be that of a relay station, transmitting neural signals primarily to the cerebral cortex from a number of brain areas. In cognition, its main contribution may thus be to coordinate signals between diverse regions of the telencephalon, including the neocortex, hippocampus, amygdala, and striatum. This central coordination is further subject to considerable extrinsic control, for example, inhibition from the basal ganglia, zona incerta, and pretectal regions, and chemical modulation from ascending neurotransmitter systems. What follows is a brief review on the role of the thalamus in aspects of cognition and behavior, focusing on a summary of the topics covered in a mini-symposium held at the Society for Neuroscience meeting, 2014.

Cognitive control of movement via the cerebellar-recipient thalamus.

The cognitive control of behavior was long considered to be centralized in cerebral cortex. More recently, subcortical structures such as cerebellum and basal ganglia have been implicated in cognitive functions as well. The fact that subcortico-cortical circuits for the control of movement involve the thalamus prompts the notion that activity in movement-related thalamus may also reflect elements of cognitive behavior. Yet this hypothesis has rarely been investigated. Using the pathways linking cerebellum to cerebral cortex via the thalamus as a template, we review evidence that the motor thalamus, together with movement-related central thalamus have the requisite connectivity and activity to mediate cognitive aspects of movement control.

Exploring the role of the substantia nigra pars reticulata in eye movements.

Experiments that demonstrated a role for the substantia nigra in eye movements have played an important role in our understanding of the function of the basal ganglia in behavior more broadly. In this review we explore more recent experiments that extend the role of the substantia nigra pars reticulata from a simple gate for eye movements to include a role in cognitive processes for eye movements. We review recent evidence suggesting that basal ganglia nuclei beyond the substantia nigra may also play a role in eye movements and the cognitive events leading up to the production of eye movements. We close by pointing out some unresolved questions in our understanding of the relationship of basal ganglia nuclei and eye movements.

The role of stimulus salience and attentional capture across the neural hierarchy in a stop-signal task.

Inhibitory motor control is a core function of cognitive control. Evidence from diverse experimental approaches has linked this function to a mostly right-lateralized network of cortical and subcortical areas, wherein a signal from the frontal cortex to the basal ganglia is believed to trigger motor-response cancellation. Recently, however, it has been recognized that in the context of typical motor-control paradigms those processes related to actual response inhibition and those related to the attentional processing of the relevant stimuli are highly interrelated and thus difficult to distinguish. Here, we used fMRI and a modified Stop-signal task to specifically examine the role of perceptual and attentional processes triggered by the different stimuli in such tasks, thus seeking to further distinguish other cognitive processes that may precede or otherwise accompany the implementation of response inhibition. In order to establish which brain areas respond to sensory stimulation differences by rare Stop-stimuli, as well as to the associated attentional capture that these may trigger irrespective of their task-relevance, we compared brain activity evoked by Stop-trials to that evoked by Go-trials in task blocks where Stop-stimuli were to be ignored. In addition, region-of-interest analyses comparing the responses to these task-irrelevant Stop-trials, with those to typical relevant Stop-trials, identified separable activity profiles as a function of the task-relevance of the Stop-signal. While occipital areas were mostly blind to the task-relevance of Stop-stimuli, activity in temporo-parietal areas dissociated between task-irrelevant and task-relevant ones. Activity profiles in frontal areas, in turn, were activated mainly by task-relevant Stop-trials, presumably reflecting a combination of triggered top-down attentional influences and inhibitory motor-control processes.