Yoko Nagai

Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a "default mode" of brain function

We examined neural activity related to modulation of skin conductance level (SCL), an index of sympathetic tone, using functional magnetic resonance imaging (fMRI) while subjects performed biofeedback arousal and relaxation tasks. Neural activity within the ventromedial prefrontal cortex (VMPFC) and the orbitofrontal cortex (OFC) covaried with skin conductance level (SCL), irrespective of task. Activity within striate and extrastriate cortices, anterior cingulate and insular cortices, thalamus, hypothalamus and lateral regions of prefrontal cortex reflected the rate of change in electrodermal activity, highlighting areas supporting transient skin conductance responses (SCRs). Successful performance of either biofeedback task (where SCL changed in the intended direction) was associated with enhanced activity in mid-OFC. The findings point to a dissociation between neural systems controlling basal sympathetic tone (SCL) and transient skin conductance responses (SCRs). The level of activity in VMPFC has been related to a default mode of brain function and our findings provide a physiological account of this state, indicating that activity within VMPFC and OFC reflects a dynamic between exteroceptive and interoceptive deployment of attention.

Brain activity relating to the contingent negative variation: an fMRI investigation

The contingent negative variation (CNV) is a long-latency electroencephalography (EEG) surface negative potential with cognitive and motor components, observed during response anticipation. CNV is an index of cortical arousal during orienting and attention, yet its functional neuroanatomical basis is poorly understood. We used functional magnetic resonance imaging (fMRI) with simultaneous EEG and recording of galvanic skin response (GSR) to investigate CNV-related central neural activity and its relationship to peripheral autonomic arousal. In a group analysis, blood oxygenation level dependent (BOLD) activity during the period of CNV generation was enhanced in thalamus, somatomotor cortex, bilateral midcingulate, supplementary motor, and insular cortices. Enhancement of CNV-related activity in anterior and midcingulate, SMA, and insular cortices was associated with decreases in peripheral sympathetic arousal. In a subset of subjects in whom we acquired simultaneous EEG and fMRI data, we observed activity in bilateral thalamus, anterior cingulate, and supplementary motor cortex that was modulated by trial-by-trial amplitude of CNV. These findings provide a likely functional neuroanatomical substrate for the CNV and demonstrate modulation of components of this neural circuitry by peripheral autonomic arousal. Moreover, these data suggest a mechanistic model whereby thalamocortical interactions regulate CNV amplitude.

Activity in the human brain predicting differential heart rate responses to emotional facial expressions

The James-Lange theory of emotion proposes that automatically generated bodily reactions not only color subjective emotional experience of stimuli, but also necessitate a mechanism by which these bodily reactions are differentially generated to reflect stimulus quality. To examine this putative mechanism, we simultaneously measured brain activity and heart rate to identify regions where neural activity predicted the magnitude of heart rate responses to emotional facial expressions. Using a forewarned reaction time task, we showed that orienting heart rate acceleration to emotional face stimuli was modulated as a function of the emotion depicted. The magnitude of evoked heart rate increase, both across the stimulus set and within each emotion category, was predicted by level of activity within a matrix of interconnected brain regions, including amygdala, insula, anterior cingulate, and brainstem. We suggest that these regions provide a substrate for translating visual perception of emotional facial expression into differential cardiac responses and thereby represent an interface for selective generation of visceral reactions that contribute to the embodied component of emotional reaction.

Clinical efficacy of galvanic skin response biofeedback training in reducing seizures in adult epilepsy: a preliminary randomized controlled study

We investigated the effect of galvanic skin response (GSR) biofeedback training on seizure frequency in patients with treatment-resistant epilepsy. Eighteen patients with drug-refractory epilepsy were randomly assigned either to an active GSR biofeedback group (n = 10) or to a sham control biofeedback group (n = 8). Biofeedback training significantly reduced seizure frequency in the active biofeedback group (P = 0.017), but not the control group (P > 0.10). This was manifest as a significant between-group difference in seizure reduction (P 0.01). Furthermore, there was a correlation between degree of improvement in biofeedback performance and reduction of seizure frequency (rho = 0.736, P = 0.001), confirming that the effect of biofeedback treatment was related to physiological change. Our findings highlight the potential therapeutic value of GSR biofeedback in reducing seizure frequency in patients with drug-resistant epilepsy.

Emotional Appraisal Is Influenced by Cardiac Afferent Information

Influential models highlight the central integration of bodily arousal with emotion. Some emotions, notably disgust, are more closely coupled to visceral state than others. Cardiac baroreceptors, activated at systole within each cardiac cycle, provide short-term visceral feedback. Here we explored how phasic baroreceptor activation may alter the appraisal of brief emotional stimuli and consequent cardiovascular reactions. We used functional MRI (fMRI) to measure brain responses to emotional face stimuli presented before and during cardiac systole. We observed that the processing of emotional stimuli was altered by concurrent natural baroreceptor activation. Specifically, facial expressions of disgust were judged as more intense when presented at systole, and rebound heart rate increases were attenuated after expressions of disgust and happiness. Neural activity within prefrontal cortex correlated with emotionality ratings. Activity within periaqueductal gray matter reflected both emotional ratings and their interaction with cardiac timing. Activity within regions including prefrontal and visual cortices correlated with increases in heart rate evoked by the face stimuli, while orbitofrontal activity reflected both evoked heart rate change and its interaction with cardiac timing. Our findings demonstrate that momentary physiological fluctuations in cardiovascular afferent information (1) influence specific emotional judgments, mediated through regions including the periaqueductal gray matter, and (2) shape evoked autonomic responses through engagement of orbitofrontal cortex. Together these findings highlight the close coupling of visceral and emotional processes and identify neural regions mediating bodily state influences on affective judgment.

How Emotions Are Shaped by Bodily States

The state of the body is central to guiding motivational behaviours. Here we discuss how afferent information from face and viscera influence the processing and communication of emotional states. We highlight (a) the fine-grained impact that facial muscular and patterned visceral responses exert on emotional appraisal and communicative signals; (b) short-term changes in visceral state that bias brain responses to emotive stimuli; (c) the commonality of brain pathways and substrates mediating short- and long-term bodily effects on emotional processes; (d) how topographically distinct representations of different bodily states are coupled to reported feelings associated with subtypes of disgust; and (e) how pupil signals contribute to affective exchange. Integrating these observations enriches our understanding of emotional processes and psychopathology.

Slow Breathing and Hypoxic Challenge: Cardiorespiratory Consequences and Their Central Neural Substrates

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge.

Changes in cortical potential associated with modulation of peripheral sympathetic activity in patients with epilepsy.

Objectives: To examine the immediate and sustained effects of volitional sympathetic modulation, using galvanic skin response (GSR) biofeedback training on cortical excitability in patients with drug-resistant epilepsy. Methods: Ten patients undertook 12 sessions of GSR biofeedback training over 1 month, during which they were trained to increase sympathetic arousal, using GSR biofeedback. Contingent negative variation (CNV) (a slow cortical potential reflecting cortical arousal and excitability) and the related post imperative negative variation (PINV) were quantified before and after biofeedback treatment. Results: A significant reduction in CNV amplitude was observed in both the short-term (within the first session, after 10 minutes of GSR biofeedback) and long-term (sustained after 12 training sessions). Specifically, the change in baseline CNV amplitude after the 12 training sessions correlated with a percentage reduction in seizure frequency. Furthermore, changes in baseline amplitude of the PINV also correlated with seizure reduction. Conclusions: Our findings demonstrate that behavioral enhancement of peripheral sympathetic tone (GSR) is associated with modulation of indices of cortical excitability. Moreover, GSR biofeedback training over repeated sessions was associated with a chronic baseline reduction in slow cortical potentials and concurrent therapeutic improvement. GSR = galvanic skin response; CNV = contingent negative variation; SCP = slow cortical potential; PINV = post imperative negative variation.

Biofeedback and Epilepsy

Biofeedback is a noninvasive behavioral treatment that enables a patient to gain volitional control over a physiological process. As a treatment for epilepsy, biofeedback interventions were explored from as early as the 1970s, concentrating on sensory motor rhythm (SMR) as a neurophysiologic parameter. Whereas SMR biofeedback aims to modulate frequency components of the electroencephalography (EEG), slow cortical potential (SCP) biofeedback (which was introduced in the 1990s) focuses on the regulation of the amplitude of cortical potential changes (DC shift). In its application to epilepsy, biofeedback using galvanic skin response (GSR), an electrodermal measure of sympathetic activity, is a relatively new cost-effective methodology. The present article first reviews biofeedback using SMR and SCP, for which efficacy and neural mechanisms are relatively well characterized. Then recent data regarding promising applications of GSR biofeedback will be introduced and discussed in detail.

The role of the autonomic nervous system in Tourette Syndrome

Tourette Syndrome (TS) is a neurodevelopmental disorder, consisting of multiple involuntary movements (motor tics) and one or more vocal (phonic) tics. It affects up to one percent of children worldwide, of whom about one third continue to experience symptoms into adulthood. The central neural mechanisms of tic generation are not clearly understood, however recent neuroimaging investigations suggest impaired cortico-striato-thalamo-cortical activity during motor control. In the current manuscript, we will tackle the relatively under-investigated role of the peripheral autonomic nervous system, and its central influences, on tic activity. There is emerging evidence that both sympathetic and parasympathetic nervous activity influences tic expression. Pharmacological treatments which act on sympathetic tone are often helpful: for example, Clonidine (an alpha-2 adrenoreceptor agonist) is often used as first choice medication for treating TS in children due to its good tolerability profile and potential usefulness for co-morbid attention-deficit and hyperactivity disorder. Clonidine suppresses sympathetic activity, reducing the triggering of motor tics. A general elevation of sympathetic tone is reported in patients with TS compared to healthy people, however this observation may reflect transient responses coupled to tic activity. Thus, the presence of autonomic impairments in patients with TS remains unclear. Effect of autonomic afferent input to cortico-striato-thalamo-cortical circuit will be discussed schematically. We additionally review how TS is affected by modulation of central autonomic control through biofeedback and Vagus Nerve Stimulation (VNS). Biofeedback training can enable a patient to gain voluntary control over covert physiological responses by making these responses explicit. Electrodermal biofeedback training to elicit a reduction in sympathetic tone has a demonstrated association with reduced tic frequency. VNS, achieved through an implanted device that gives pulsatile electrical stimulation to the vagus nerve, directly modulates afferent interoceptive signals. The potential efficacy of biofeedback/VNS in TS and the implications for understanding the underlying neural mechanisms of tics will be discussed.