Sarah N. Garfinkel

Knowing your own heart: Distinguishing interoceptive accuracy from interoceptive awareness

Interoception refers to the sensing of internal bodily changes. Interoception interacts with cognition and emotion, making measurement of individual differences in interoceptive ability broadly relevant to neuropsychology. However, inconsistency in how interoception is defined and quantified led to a three-dimensional model. Here, we provide empirical support for dissociation between dimensions of: (1) interoceptive accuracy (performance on objective behavioural tests of heartbeat detection), (2) interoceptive sensibility (self-evaluated assessment of subjective interoception, gauged using interviews/questionnaires) and (3) interoceptive awareness (metacognitive awareness of interoceptive accuracy, e.g. confidence-accuracy correspondence). In a normative sample (N=80), all three dimensions were distinct and dissociable. Interoceptive accuracy was only partly predicted by interoceptive awareness and interoceptive sensibility. Significant correspondence between dimensions emerged only within the sub-group of individuals with greatest interoceptive accuracy. These findings set the context for defining how the relative balance of accuracy, sensibility and awareness dimensions explain cognitive, emotional and clinical associations of interoceptive ability.

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

BACKGROUND Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. METHODS Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. RESULTS Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. LIMITATIONS Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non-combat related PTSD. CONCLUSION These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.

Neural Dysregulation in Posttraumatic Stress Disorder: Evidence for Disrupted Equilibrium between Salience and Default Mode Brain Networks

Objective Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]). Methods Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain. Results Compared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected). Conclusions During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.

Impaired Contextual Modulation of Memories in PTSD: An fMRI and Psychophysiological Study of Extinction Retention and Fear Renewal

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.

Fear from the heart: sensitivity to fear stimuli depends on individual heartbeats.

Cognitions and emotions can be influenced by bodily physiology. Here, we investigated whether the processing of brief fear stimuli is selectively gated by their timing in relation to individual heartbeats. Emotional and neutral faces were presented to human volunteers at cardiac systole, when ejection of blood from the heart causes arterial baroreceptors to signal centrally the strength and timing of each heartbeat, and at diastole, the period between heartbeats when baroreceptors are quiescent. Participants performed behavioral and neuroimaging tasks to determine whether these interoceptive signals influence the detection of emotional stimuli at the threshold of conscious awareness and alter judgments of emotionality of fearful and neutral faces. Our results show that fearful faces were detected more easily and were rated as more intense at systole than at diastole. Correspondingly, amygdala responses were greater to fearful faces presented at systole relative to diastole. These novel findings highlight a major channel by which short-term interoceptive fluctuations enhance perceptual and evaluative processes specifically related to the processing of fear and threat and counter the view that baroreceptor afferent signaling is always inhibitory to sensory perception.

What the heart forgets: cardiac timing influences memory for words and is modulated by metacognition and interoceptive sensitivity

Mental functions are influenced by states of physiological arousal. Afferent neural activity from arterial baroreceptors at systole conveys the strength and timing of individual heartbeats to the brain. We presented words under limited attentional resources time-locked to different phases of the cardiac cycle, to test a hypothesis that natural baroreceptor stimulation influences detection and subsequent memory of words. We show memory for words presented around systole was decreased relative to words at diastole. The deleterious memory effect of systole was greater for words detected with low confidence and amplified in individuals with low interoceptive sensitivity, as indexed using a heartbeat counting task. Our observations highlight an important cardiovascular channel through which autonomic arousal impacts a cognitive function, an effect mitigated by metacognition (perceptual confidence) and interoceptive sensitivity.

DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA’s antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA’s impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects.

Threat and the Body: How the Heart Supports Fear Processing

Mental processes depend upon a dynamic integration of brain and body. Emotions encompass internal physiological changes which, through interoception (sensing bodily states), underpin emotional feelings, for example, cardiovascular arousal can intensify feelings of fear and anxiety. The brain is informed about how quickly and strongly the heart is beating by signals from arterial baroreceptors. These fire in bursts after each heartbeat, and are quiet between heartbeats. The processing of fear stimuli is selectively enhanced by these phasic signals, and these inhibit the processing of other types of stimuli including physical pain. Behavioural and neuroimaging studies detail this differential impact of heart signals on the processing of salient stimuli, and add to knowledge linking rhythmic activity in brain and body to perceptual consciousness.

Alterations in Amygdala-Prefrontal Functional Connectivity Account for Excessive Worry and Autonomic Dysregulation in Generalized Anxiety Disorder

BACKGROUND Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism. METHODS We used resting-state functional magnetic resonance imaging and the measurement of parasympathetic autonomic function (heart rate variability) in 19 patients with GAD and 21 control subjects to define neural correlates of autonomic and cognitive responses before and after induction of perseverative cognition. Seed-based analyses were conducted to quantify brain changes in functional connectivity with the right and left amygdala. RESULTS Before induction, patients showed relatively lower connectivity between the right amygdala and right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus than control subjects. After induction, such connectivity patterns increased in patients with GAD and decreased in control subjects, and these changes tracked increases in state perseverative cognition. Moreover, decreases in functional connectivity between the left amygdala and subgenual cingulate cortex and between the right amygdala and caudate nucleus predicted the magnitude of reduction in heart rate variability after induction. CONCLUSIONS Our results link functional brain mechanisms underlying worry and rumination to autonomic dyscontrol, highlighting overlapping neural substrates associated with cognitive and autonomic responses to the induction of perseverative cognitions in patients with GAD.

Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility

Objective: Anxiety is associated with increased physiological reactivity and also increased “interoceptive” sensitivity to such changes in internal bodily arousal. Joint hypermobility, an expression of a common variation in the connective tissue protein collagen, is increasingly recognized as a risk factor to anxiety and related disorders. This study explored the link between anxiety, interoceptive sensitivity and hypermobility in a sub-clinical population using neuroimaging and psychophysiological evaluation. Methods: Thirty-six healthy volunteers undertook interoceptive sensitivity tests, a clinical examination for hypermobility and completed validated questionnaire measures of state anxiety and body awareness tendency. Nineteen participants also performed an emotional processing paradigm during functional neuroimaging. Results: We confirmed a significant relationship between state anxiety score and joint hypermobility. Interoceptive sensitivity mediated the relationship between state anxiety and hypermobility. Hypermobile, compared to non-hypermobile, participants displayed heightened neural reactivity to sad and angry scenes within brain regions implicated in anxious feeling states, notably insular cortex. Conclusions: Our findings highlight the dependence of anxiety state on bodily context, and increase our understanding of the mechanisms through which vulnerability to anxiety disorders arises in people bearing a common variant of collagen.