Eric C. Porges

Imagining being the agent of actions that carry different moral consequences: An fMRI study

To investigate the contribution of agency to neural processing involved in aggression and morality, participants viewed in the MRI scanner a series of short visual scenarios in which an individual was either intentionally harming another person or easing the others pain. They were required to mentally simulate being the perpetrator or the recipient of those actions. Functional connectivity analyses demonstrate that positive agency (easing the pain of another) was associated with increased activity in ventral striatum, while negative agency (harming the other) resulted in a strong signal decrease in the ventromedial prefrontal cortex and activation in the amygdala. Overall, our data show that explicit perspective taking strategy has profound impact on the neural recruitment associated with distinct behaviors as well as their moral consequences. Results from this study can inform new strategies both for therapeutic interventions for patients with socioemotional disorders and the education of medical practitioners.

Oxytocin receptor gene variation predicts empathic concern and autonomic arousal while perceiving harm to others

Recent research indicates that the neuropeptide oxytocin and the gene for the oxytocin receptor (OXTR) have been implicated in the modulation of various social behaviors, including those related to empathy and sensitivity to others. In this study, we examine the hypothesis that genetic variation in OXTR is associated with autonomic reactions when perceiving others in distress. We also explore the possibility that individual disposition in empathic concern would differ by OXTR genotype. To address these questions, 51 male participants (18–35 years of age), genotyped for OXTR rs53576, viewed a social interaction containing high levels of individual distress and apparent physical pain. Electrodermal activity, a measure of sympathetic nervous system activity, was collected during the presentation of the stimuli. Participants also completed a self-report dispositional measure of empathy prior to starting the study and provided ratings of arousal while viewing the stimuli. OXTR variant rs53576 GG individuals showed increased levels of sympathetic and subjective arousal in response to the stimuli compared to A allele carriers. GG homozygotes also expressed greater levels of empathic concern. These findings support the importance of the oxytocin receptor variation in emotional and physiological reactions to the affective experiences of other conspecifics.

Maladaptive autonomic regulation in PTSD accelerates physiological aging

A core manifestation of post-traumatic stress disorder (PTSD) is a disconnection between physiological state and psychological or behavioral processes necessary to adequately respond to environmental demands. Patients with PTSD experience abnormal oscillations in autonomic states supporting either fight and flight behaviors or withdrawal, immobilization, and dissociation without an intervening “calm” state that would provide opportunities for positive social interactions. This defensive autonomic disposition is adaptive in dangerous and life threatening situations, but in the context of every-day life may lead to significant psychosocial distress and deteriorating social relationships. The perpetuation of these maladaptive autonomic responses may contribute to the development of comorbid mental health issues such as depression, loneliness, and hostility that further modify the nature of cardiovascular behavior in the context of internal and external stressors. Over time, changes in autonomic, endocrine, and immune function contribute to deteriorating health, which is potently expressed in brain dysfunction and cardiovascular disease. In this theoretical review paper, we present an overview of the literature on the chronic health effects of PTSD. We discuss the brain networks underlying PTSD in the context of autonomic efferent and afferent contributions and how disruption of these networks leads to poor health outcomes. Finally, we discuss treatment approaches based on our theoretical model of PTSD.

Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a nonforensic sample

Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a nonforensic sample are linked to amygdala response to violence, this study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self‐Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. Hum Brain Mapp 36:1417–1428, 2015.

A possible mechanism for PTSD symptoms in patients with traumatic brain injury: central autonomic network disruption

Patients with traumatic brain injuries (TBI) often develop post traumatic stress disorder (PTSD). This syndrome, defined and diagnosed by psychological and behavioral features, is associated with symptoms such as anxiety and anger with an increase of arousal and vigilance, as well as flashbacks and nightmares. Many of these features and symptoms observed in PTSD may be in part the result of altered autonomic nervous system (ANS) activity in response to psychological and physical challenges. Brain imaging has documented that TBI often induces white matter damage to pathways associated with the anterior limb of the internal capsule and uncinate fasciculus. Since these white matter structures link neocortical networks with subcortical and limbic structures that regulate autonomic control centers, injury to these pathways may induce a loss of inhibitory control of the ANS. In this review, the autonomic features associated with PTSD are discussed in the context of traumatic brain injury. We posit that TBI induced damage to networks that regulate the ANS increase vulnerability to PTSD. The means by which the vulnerability can be measured and tested are also discussed.

Utilization of central nervous system resources for preparation and performance of complex walking tasks in older adults

Introduction: Walking in the home and community often involves performance of complex walking tasks. Understanding the control of such tasks is crucial to preserving independence and quality of life in older adults. However, very little research has been conducted in this area. Here, we assess the extent to which two measures of central nervous system (CNS) activity are responsive to the challenges posed by preparation and performance of complex walking tasks. Prefrontal cortical activity was measured by functional near-infrared spectroscopy (fNIRS) and sympathetic nervous system arousal was measured by skin conductance level (SCL). Materials and methods: Sixteen older men and women (age: 77.2 ± 5.6 years) with mild mobility deficits participated in this study. Participants walked at their preferred speed without distractions along an unobstructed, well-lit course (control task) and also walked on the same course under five separate challenging conditions: performing a cognitive verbal fluency task (verbal task), dim lighting (dim task), carrying a tray (carry task), negotiating obstacles (obstacles task) and wearing a weighted vest (vest task). Mean prefrontal activation and SCL were calculated during the preparation and performance phases of each task. Gait spatiotemporal measurements were acquired by an instrumented gait mat. Results: Prefrontal cortical activity and SCL were elevated during the preparation phase of complex walking tasks relative to the control task. During the performance phase, prefrontal activity remained elevated to a similar level as during task preparation. In contrast, SCL continued to increase beyond the level observed during task preparation. A larger increase in prefrontal activity was found to be linked to preserved quality of gait during complex walking tasks. Discussion: These findings indicate that availability and utilization of CNS resources are important for optimizing performance of complex walking tasks in older adults.

Oxytocin’s effect on resting-state functional connectivity varies by age and sex

The neuropeptide oxytocin plays a role in social cognition and affective processing. The neural processes underlying these effects are not well understood. Modulation of connectivity strength between subcortical and cortical regions has been suggested as one possible mechanism. The current study investigated effects of intranasal oxytocin administration on resting-state functional connectivity between amygdala and medial prefrontal cortex (mPFC), as two regions involved in social-cognitive and affective processing. Going beyond previous work that largely examined young male participants, our study comprised young and older men and women to identify age and sex variations in oxytocins central processes. This approach was based on known hormonal differences among these groups and emerging evidence of sex differences in oxytocins effects on amygdala reactivity and age-by-sex-modulated effects of oxytocin in affective processing. In a double-blind design, 79 participants were randomly assigned to self-administer either intranasal oxytocin or placebo before undergoing resting-state functional magnetic resonance imaging. Using a targeted region-to-region approach, resting-state functional connectivity strength between bilateral amygdala and mPFC was examined. Participants in the oxytocin compared to the placebo group and men compared to women had overall greater amygdala-mPFC connectivity strength at rest. These main effects were qualified by a significant three-way interaction: while oxytocin compared to placebo administration increased resting-state amygdala-mPFC connectivity for young women, oxytocin did not significantly influence connectivity in the other age-by-sex subgroups. This study provides novel evidence of age-by-sex differences in how oxytocin modulates resting-state brain connectivity, furthering our understanding of how oxytocin affects brain networks at rest.

Frontal Structural Neural Correlates of Working Memory Performance in Older Adults

Working memory is an executive memory process that allows transitional information to be held and manipulated temporarily in memory stores before being forgotten or encoded into long-term memory. Working memory is necessary for everyday decision-making and problem solving, making it a fundamental process in the daily lives of older adults. Working memory relies heavily on frontal lobe structures and is known to decline with age. The current study aimed to determine the neural correlates of decreased working memory performance in the frontal lobes by comparing cortical thickness and cortical surface area from two demographically matched groups of healthy older adults, free from cognitive impairment, with high versus low N-Back working memory performance (N = 56; average age = 70.29 ± 10.64). High-resolution structural T1-weighted images (1 mm isotropic voxels) were obtained on a 3T Philips MRI scanner. When compared to high performers, low performers exhibited significantly decreased cortical surface area in three frontal lobe regions lateralized to the right hemisphere: medial orbital frontal gyrus, inferior frontal gyrus, and superior frontal gyrus (FDR p < 0.05). There were no significant differences in cortical thickness between groups, a proxy for neurodegenerative tissue loss. Our results suggest that decreases in cortical surface area (a proxy for brain structural integrity) in right frontal regions may underlie age-related decline of working memory function.

Cognitive Aging and the Hippocampus in Older Adults.

The hippocampus is one of the most well studied structures in the human brain. While age-related decline in hippocampal volume is well documented, most of our knowledge about hippocampal structure-function relationships was discovered in the context of neurological and neurodegenerative diseases. The relationship between cognitive aging and hippocampal structure in the absence of disease remains relatively understudied. Furthermore, the few studies that have investigated the role of the hippocampus in cognitive aging have produced contradictory results. To address these issues, we assessed 93 older adults from the general community (mean age = 71.9 ± 9.3 years) on the Montreal Cognitive Assessment (MoCA), a brief cognitive screening measure for dementia, and the NIH Toolbox-Cognitive Battery (NIHTB-CB), a computerized neurocognitive battery. High-resolution structural magnetic resonance imaging (MRI) was used to estimate hippocampal volume. Lower MoCA Total (p = 0.01) and NIHTB-CB Fluid Cognition (p < 0.001) scores were associated with decreased hippocampal volume, even while controlling for sex and years of education. Decreased hippocampal volume was significantly associated with decline in multiple NIHTB-CB subdomains, including episodic memory, working memory, processing speed and executive function. This study provides important insight into the multifaceted role of the hippocampus in cognitive aging.

Individual differences in vagal regulation are related to testosterone responses to observed violence.

Observing violent content has been hypothesized to facilitate antisocial behaviors including interpersonal violence. Testosterone is released in response to perceived challenges of social status, often followed by an increase in aggressive behaviors and physiological activation. Prior investigations evaluating the impact of observing violence on autonomic function have focused on sympathetic measures of arousal. Measurement of parasympathetic nervous system (PNS) activity has been neglected, although reduced PNS activity has been associated with antisocial behavior. Consistent with a hierarchical model of the autonomic nervous system (i.e., polyvagal theory), individual differences in PNS activity reflected in respiratory sinus arrhythmia (RSA) were hypothesized to have an inhibitory impact on sympathetic and hormonal reactivity in subjects who were observing a violent video. Autonomic data (i.e., electrodermal activity (EDA), heart rate, and RSA) were collected from forty adult males prior to and while viewing violent sports or a control video. Pre- and post-video saliva samples were assayed for cortisol and testosterone. Participants who viewed the violent video showed increased sympathetic activity compared to controls. In contrast to the sympathetic reactivity to the violent video, there were no significant RSA changes in response to the stimuli, suggesting that viewing violent sports selectively increases sympathetic activity without eliciting PNS withdrawal. However, within the group viewing the violent video, participants with lower RSA during baseline and the observation of violent videos, responded with greater increases in salivary testosterone, suggesting that high parasympathetic tone dampens testosterone reactivity. These individual differences in response to observed violence, associated with higher RSA, may account for some of the improved health, growth, and restoration outcomes across the lifespan, that this segment of the population benefits from.