Damon G. Lamb

Social isolation disrupts autonomic regulation of the heart and influences negative affective behaviors.

BACKGROUND There is a documented association between affective disorders (e.g., depression and anxiety) and cardiovascular disease in humans. Chronic social stressors may play a mechanistic role in the development of behavioral and cardiac dysregulation. The current study investigated behavioral, cardiac, and autonomic responses to a chronic social stressor in prairie voles, a rodent species that displays social behaviors similar to humans. METHODS Female prairie voles were exposed to 4 weeks of social isolation (n = 8) or pairing (control conditions; n = 7). Electrocardiographic parameters were recorded continuously during isolation, and behavioral tests were conducted during and following this period. RESULTS Isolation induced a significant increase in resting heart rate, reduction in heart rate variability (standard deviation of normal-to-normal intervals and amplitude of respiratory sinus arrhythmia), and exaggerated cardiac responses during an acute resident-intruder paradigm. Isolation led also to both depression-like and anxiety-like behaviors in validated operational tests. These changes in response to social isolation showed predictable interrelations and were mediated by a disruption of autonomic balance including both sympathetic and parasympathetic (vagal) mechanisms. CONCLUSIONS These findings indicate that social isolation induces behavioral, cardiac, and autonomic alterations related to those seen after other stressors and which are relevant to cardiovascular disease and affective disorders. This model may provide insight into the mechanisms that underlie these co-occurring conditions.

Cardiac regulation in the socially monogamous prairie vole

Social experiences, both positive and negative, may influence cardiovascular regulation. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form social bonds similar to those seen in primates, and this species may provide a useful model for investigating neural and social regulation of cardiac function. Cardiac regulation has not been studied previously in the prairie vole. Radiotelemetry transmitters were implanted into adult female prairie voles under anesthesia, and electrocardiographic parameters were recorded. Autonomic blockade was performed using atenolol (8 mg/kg ip) and atropine methyl nitrate (4 mg/kg ip). Several variables were evaluated, including heart rate (HR), HR variability and the amplitude of respiratory sinus arrhythmia. Sympathetic blockade significantly reduced HR. Parasympathetic blockade significantly increased HR, and reduced HR variability and the amplitude of respiratory sinus arrhythmia. Combined autonomic blockade significantly increased HR, and reduced HR variability and respiratory sinus arrhythmia amplitude. The data indicate that autonomic function in prairie voles shares similarities with primates, with a predominant vagal influence on cardiac regulation. The current results provide a foundation for studying neural and social regulation of cardiac function during different behavioral states in this socially monogamous rodent model.

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.

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.

Autonomic predictors of recovery following surgery: A comparative study

Although heart rate and temperature are continuously monitored in patients during recovery following surgery, measures that extract direct manifestations of neural regulation of autonomic circuits from the beat-to-beat heart rate may be more sensitive to outcome. We explore the relationship between features of autonomic regulation and survival in the prairie vole, a small mammal, with features of vagal regulation of the heart similar to humans. Cardiac vagal regulation is manifested in the beat-to-beat heart rate variability (HRV) pattern and can be quantified by extracting measures of the amplitude of periodic oscillations associated with spontaneous breathing. Thus, monitoring beat-to-beat heart rate patterns post-surgery in the prairie vole may provide an opportunity to dynamically assess autonomic adjustments during recovery. Surgeries to implant telemetry devices to monitor body temperature and continuous ECG in prairie voles are routinely performed in our laboratory. Ten of these implanted prairie voles died within 48 h post-surgery. To compare the post-surgery autonomic trajectories with typical surviving prairie voles, the post-surgery data from 17 surviving prairie voles were randomly selected. The data are reported hourly for 27 prairie voles between 6 and 14 h (1h before the demise of the first subject) post-surgery. Receiver operator curves were calculated hourly for each variable to evaluate sensitivity in discriminating survival. The data illustrate that measures of HRV are the most sensitive indicators. These findings provide a foundation for investigating further neural mechanisms of cardiovascular function.

Impact of tissue correction strategy on GABA-edited MRS findings

&NA; Tissue composition impacts the interpretation of magnetic resonance spectroscopy metabolite quantification. The goal of applying tissue correction is to decrease the dependency of metabolite concentrations on the underlying voxel tissue composition. Tissue correction strategies have different underlying assumptions to account for different aspects of the voxel tissue fraction. The most common tissue correction is the CSF‐correction that aims to account for the cerebrospinal fluid (CSF) fraction in the voxel, in which it is assumed there are no metabolites. More recently, the &agr;‐correction was introduced to account for the different concentrations of GABA+in gray matter and white matter. In this paper, we show that the selected tissue correction strategy can alter the interpretation of results using data from a healthy aging cohort with GABA+ measurements in a frontal and posterior voxel. In a frontal voxel, we show an age‐related decline in GABA+ when either no tissue correction (R2 = 0.25, p < 0.001) or the CSF‐correction is applied (R2 = 0.08, p < 0.01). When applying the &agr;‐correction to the frontal voxel data, we find no relationship between age and GABA+ (R2 = 0.02, p = 0.15). However, with the &agr;‐correction we still find that cognitive performance is correlated with GABA+ (R2 = 0.11, p < 0.01). These data suggest that in healthy aging, while there is normal atrophy in the frontal voxel, GABA+ in the remaining tissue is not decreasing on average. This indicates that the selection of tissue correction can significantly impact the interpretation of MRS results. HighlightsThe selection of tissue correction approach can fundamentally impact the interpretation of GABA+ results.In the frontal region, overall tissue volume decreases with age but GABA+ in the remaining tissue does not decrease with age.In frontal regions, GABA+ correlates with MoCA, a marker of cognitive function.This work support the use of the &agr;‐correction for GABA+ ‐MRS.

Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence

Posttraumatic stress disorder (PTSD) is a reaction to trauma that results in a chronic perception of threat, precipitating mobilization of the autonomic nervous system, and may be reflected by chronic disinhibition of limbic structures. A common injury preceding PTSD in veterans is mild traumatic brain injury (mTBI). This may be due to the vulnerability of white matter in these networks and such damage may affect treatment response. We evaluated transcutaneous vagal nerve stimulation (tVNS), a non-invasive, low-risk approach that may alter the functions of the limbo-cortical and peripheral networks underlying the hyperarousal component of PTSD and thus improve patient health and well-being. In this single visit pilot study evaluating the impact of tVNS in 22 combat veterans, we used a between-subjects design in people with either PTSD with preceding mTBI or healthy controls. Participants were randomized into stimulation or sham groups and completed a posturally modulated autonomic assessment and emotionally modulated startle paradigm. The primary measures used were respiratory sinus arrhythmia (high-frequency heart rate variability) during a tilt-table procedure derived from an electrocardiogram, and skin conductance changes in response to acoustic startle while viewing emotional images (International Affective Picture System). The stimulation was well tolerated and resulted in improvements in vagal tone and moderation of autonomic response to startle, consistent with modulation of autonomic state and response to stress in this population. Our results suggest that tVNS affects systems underlying emotional dysregulation in this population and, therefore, should be further evaluated and developed as a potential treatment tool for these patients.

The influence of stimulus proximity on judgments of spatial relationships in patients with chronic unilateral right or left hemisphere stroke

Objective: This was to learn how chronic right hemispheric damage (RHD) versus left hemispheric damage (LHD) may influence attentional biases in proximal and distal space. Background: Prior research has suggested that the left hemisphere primarily attends to proximal space and the right hemisphere to distal space. The purpose of this study was to contrast line bisection performed in proximal versus distal space in patients with chronic LHD versus RHD. Design/method: Participants were 32 LHD and 26 RHD patients who sustained a stroke a mean of 3.4 years prior to testing, along with 9 healthy controls. Subjects attempted to bisect 30 lines in proximal space and 30 lines in distal space. Results: Patients with both RHD and LHD had a greater contralesional bias in proximal than distal space (rightward bias for patients with LHD and leftward bias for patients with RHD). Compared to controls, patients with LHD were most different in proximal space, and patients with RHD were most different in distal space. Conclusions: Proximity appears to influence spatial judgments of patients with RHD and LHD in an opposing manner. Relatively, both patient groups bisect lines contralesionally in proximal space and ipsilesionally (relative to proximal) in distal space. Patients with RHD have the biggest difference between their proximal and distal judgments. The reason for these differences is unknown. However, these biases may be related to an attentional or action-intentional grasp or a learned compensation strategy, and proximity may increase the allocation of attention or intention and thereby enhance this grasp or use of this compensation strategy. Another contributing factor may be dominance of the left and right hemisphere for information presented in proximal and distal space, respectively.

The aging brain: Movement speed and spatial control

BACKGROUND/OBJECTIVES With aging, people commonly develop motor slowing (bradykinesia). Although this slowness with aging may be entirely related to degradation of the cerebral networks important in motor programing, it is possible that, at least in part, it may be a learned procedure for enhancing the accuracy and/or precision of movements. The goal of this study is to test these contradictory hypotheses. METHODS Twenty-four healthy adults, 12 younger than age 26 and 12 older than age 65 were asked to make alternative marks with a pen between a card centered in front of them and a series of circles distributed across a page. Performance was timed, and participants were instructed to complete the task as quickly as possible while not sacrificing accuracy for speed. The circle sizes and hand used varied by trial. RESULTS The older adults performed the task more slowly for all target circle diameters. As the circles decreased in size, the younger adults performed the task more rapidly than did the older participants, but the younger participants also had a greater decline in accuracy. CONCLUSIONS During this aiming task, healthy older adults were less likely than younger adults to sacrifice accuracy for speed. Thus, at least in part, their slowing may be a learned adaptive strategy.

Asymmetrical distractibility of global and focal visuospatial attention during segmental and total compound line bisections.

Background/Objectives: Compound horizontal lines are composed of 2 segments of unequal length and width. Line bisection requires that the participants attend to the entire line (global attention). The longer segment often distracts participants, suggesting that attention directed to this segment (focal attention) disrupts the allocation of global attention. This study attempted to learn whether the allocation of focal attention to a line segment is distracted by global attention allocated to the entire line and whether there are right-left distraction asymmetries when allocating focal or global attention. Method: Twenty-four healthy adults (12 > 65 years old) attempted to bisect horizontal lines composed of 2 segments of unequal length, with the larger segment placed to the right or left. They were also asked to bisect the longer segment of these lines. Results: When allocating focal attention to the larger segment, healthy participants were more distracted when the smaller segment was on the left than on the right. In contrast, when attempting to allocate global attention to the entire line, participants were more distracted when the larger segment was on the right side. There were no significant differences between older and younger participants. Conclusions: The asymmetrical global distraction during segment bisection might be related to the right hemisphere’s dominance in mediating global attention and allocating attention leftward. In contrast, the asymmetrical focal distraction during full-line bisection might be related to the left hemisphere’s dominance in mediating focal attention and allocating attention toward the right.