Stroke Severity, Caregiver Feedback, and Cognition in the REGARDS-CARES Study.

Objective: Cognitive impairment after stroke is common, present up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of two stroke severity ratings and a caregiver-report of post-stroke functioning with longitudinal cognitive outcomes. Methods: The analysis was conducted on 157 caregivers and stroke survivor dyads who participated in the Caring for Adults Recovering from the Effects of Stroke (CARES) project, an ancillary study of the REasons for Geographic and Racial Differences in Stroke (REGARDS) national cohort study. Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) collected at hospitalization discharge were included as two primary predictors of cognitive impairment. The number of caregiver-reported problems and impairments at nine months following stroke were included as a third predictor. Cognition was assessed using a biennial telephone battery, incorporating multiple cognitive assessments to assess learning, memory, and executive functioning. Longitudinal cognitive scores were analyzed up to five years post-stroke, controlling for baseline (pre-stroke) cognitive scores and demographic variables of each stroke survivor collected at CARES baseline. Results: Separate mixed models showed significant main effects of GOS (b=0.3280, p=0.0009), mRS (b=-0.2119, p=0.0002), and caregiver-reported impairments (b=-0.0671, p<0.0001) on longitudinal cognitive scores. In a combined model including all three predictors, only caregiver-reported problems significantly predicted cognitive outcomes (b=-0.0480, p<0.0001). Impact: These findings underscore the importance of incorporating caregivers feedback in understanding cognitive consequences of stroke.

Hippocampal volume varies with acute posttraumatic stress symptoms following medical trauma.

The hippocampus and amygdala play an important role in the pathophysiology of posttraumatic stress disorder (PTSD). In fact, chronic PTSD has been consistently linked to reductions in hippocampal and amygdala volume. However, the acute impact posttraumatic stress has on the volume of these brain regions has received limited attention. Determining the acute impact posttraumatic stress has on brain volume may improve our understanding of the development of PTSD. Therefore, the present study recruited participants acutely (i.e., ∼1-month posttrauma) following trauma exposure and examined the relationship between brain volume (assessed at ∼1-month posttrauma) and posttraumatic stress symptoms (assessed at ∼1 and >3-months posttrauma) to determine whether brain volume was associated with acute posttraumatic stress symptom expression. Twenty-one trauma-exposed (TE) patients and 19 nontrauma-exposed (NTE) controls were recruited for the present study. Brain volume was assessed by structural magnetic resonance imaging completed during the ∼1-month assessment. Left hippocampal volumes were smaller in TE than NTE participants. Among TE participants, bilateral hippocampal volumes decreased as the number of days posttrauma increased. Further, bilateral hippocampal volumes varied negatively with the severity of posttraumatic stress symptoms at ∼1-month posttrauma. The present findings suggest that there is a progressive decrease in hippocampal volume acutely (e.g., within approximately 1 month) following trauma exposure, and demonstrates that acutely assessed hippocampal volumes vary with posttraumatic stress symptom expression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

White matter microstructure varies with post-traumatic stress severity following medical trauma.

The prefrontal cortex, amygdala, hippocampus, and hypothalamus are important components of the neural network that mediates the healthy learning, expression, and regulation of emotion. These brain regions are connected by white matter pathways that include the cingulum bundle, uncinate fasciculus, and fornix/stria terminalis. Individuals with trauma and stress-related disorders show dysfunction of the cognitive-affective processes supported by the brain regions these white matter tracts connect. Therefore, variability in the microstructure of these white matter pathways may play an important role in the cognitive-affective dysfunction related to post-traumatic stress disorder. Thus, the current study used diffusion weighted imaging to assess the white matter microstructure of the cingulum bundle, uncinate fasciculus, and fornix/stria terminalis acutely (< 1 month) following trauma. Further, we assessed both acute (i.e., < 1 month) and subacute (i.e., 3 months post-trauma) post-traumatic stress symptom severity. White matter microstructure (assessed < 1 month post-trauma) of the uncinate fasciculus and fornix/stria terminalis varied with acute post-traumatic stress severity (assessed < 1 month post-trauma). Further, white matter microstructure (assessed < 1 month post-trauma) of the cingulum bundle and fornix/stria terminalis varied with subacute post-traumatic stress severity (assessed 3 months post-trauma). The current results suggest white matter architecture of the prefrontal cortex - amygdala network plays an important role in the development of trauma and stress-related disorders.

Trauma exposure acutely alters neural function during Pavlovian fear conditioning.

Posttraumatic stress disorder (PTSD) is associated with dysfunction of the neural circuitry that supports fear learning and memory processes. However, much of what is known about neural dysfunction in PTSD is based on research in chronic PTSD populations. Less is known about neural function that supports fear learning acutely following trauma exposure. Determining the acute effects of trauma exposure on brain function would provide new insight into the neural processes that mediate the cognitive-affective dysfunction associated with PTSD. Therefore, the present study investigated neural activity that supports fear learning and memory processes in recently Trauma-Exposed (TE) and Non-Trauma-Exposed (NTE) participants. Participants completed a Pavlovian fear conditioning procedure during functional magnetic resonance imaging (fMRI). During fMRI, participants' threat expectancy was continuously monitored. NTE participants showed greater threat expectancy during warning than safety cues, while no difference was observed in the TE group. This finding suggests TE participants overgeneralized the fear association to the safety cue. Further, only the TE group showed a negative relationship between fMRI signal responses within dorsomedial prefrontal cortex (PFC) and threat expectancy during safety cues. These results suggest the dorsomedial PFC mediates overgeneralization of learned fear as an acute result of trauma exposure. Finally, neural activity within the PFC and inferior parietal lobule showed a negative relationship with PTSD symptom severity assessed three months posttrauma. Thus, neural activity measured acutely following trauma exposure predicted future PTSD symptom severity. The present findings elucidate the acute effects of trauma exposure on cognitive-affective function and provide new insight into the neural mechanisms of PTSD.

Glutamate/glutamine concentrations in the dorsal anterior cingulate vary with Post-Traumatic Stress Disorder symptoms.

Trauma and stress-related disorders (e.g., Acute Stress Disorder; ASD and Post-Traumatic Stress Disorder; PTSD) that develop following a traumatic event are characterized by cognitive-affective dysfunction. The cognitive and affective functions disrupted by stress disorder are mediated, in part, by glutamatergic neural systems. However, it remains unclear whether neural glutamate concentrations, measured acutely following trauma, vary with ASD symptoms and/or future PTSD symptom expression. Therefore, the current study utilized proton magnetic resonance spectroscopy (1H-MRS) to investigate glutamate/glutamine (Glx) concentrations within the dorsal anterior cingulate cortex (ACC) of recently (i.e., within one month) traumatized individuals and non-traumatized controls. Although Glx concentrations within dorsal ACC did not differ between recently traumatized and non-traumatized control groups, a positive linear relationship was observed between Glx concentrations and current stress disorder symptoms in traumatized individuals. Further, Glx concentrations showed a positive linear relationship with future stress disorder symptoms (i.e., assessed 3 months post-trauma). The present results suggest glutamate concentrations may play a role in both acute and future post-traumatic stress symptoms following a traumatic experience. The current results expand our understanding of the neurobiology of stress disorder and suggest glutamate within the dorsal ACC plays an important role in cognitive-affective dysfunction following a traumatic experience.