Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction

Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.’s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.’s operation in the context of the brain’s overall pathology

The impact of personality on memory function in older adults—results from the Longitudinal Aging Study Amsterdam

Objective: The aim of the study was to explore associations between memory function and the personality constructs mastery, self-efficacy, and neuroticism in a large cohort of older adults over a 14-year period. Methods: Memory function and personality traits were assessed every three years for 14 years. Data was derived from the Longitudinal Aging Study Amsterdam (LASA). The study cohort included a total of 1966 men and women aged 65 and older at baseline. Episodic memory was assessed with a modified Dutch version of the Rey Auditory Verbal Learning Test. Personality was measured with Dutch versions of the Pearlin Mastery Scale, General Self-Efficacy Scale, and an abbreviated version of the Dutch Personality Questionnaire. All three personality questionnaires are self-rating instruments. Results: Higher levels of mastery and self-efficacy were associated with better memory function while high neuroticism was associated with poorer memory. Personality traits did not affect the rate of memory decline over time. Conclusions: Results demonstrate the role personality constructs, in particular those related to control beliefs and proneness to psychological stress, play in cognitive function in older adults, and support the development of intervention programs. Targeted training has the potential to promote a sense of control over life outcomes and to lower stress in older adults who are at risk for impaired memory function

Severe anterograde amnesia in the era of smartphone technology

A.V. is a young Herpes simplex Encephalitis (HSE) survivor with extensive bilateral damage to the medial temporal lobe (MTL) and one of the most severe forms of anterograde amnesia on record. In spite of the demonstrable deficit, A.V. regained a much higher degree of functioning and autonomy than previously-documented amnesic patients with major bilateral MTL damage. The distinguishing feature of A.V.’s adaptation and his advantage as a millennial, is that he is able to offload onto his smartphone those cognitive tasks that were previously supported by the MTL, as evidenced by our analysis of app usage. The topography of A.V.’s brain injury combined with purity of the ensuing amnesia represent unique neuropsychological conditions that can advance the scientific study of human memory systems. A.V.’s relative success in coping with profound amnesia further offers unique insight into the potential of smartphone technology to become integrated with neural mnemonic functions, a phenomenon that has broad implications at the societal level and for public health, specifically in the management of memory disorders like Alzheimer’s disease

Effects of Noninvasive Cervical Vagal Nerve Stimulation on Cognitive Performance But Not Brain Activation in Healthy Adults.

ObjectivesWhile preliminary evidence suggests that noninvasive vagal nerve stimulation (nVNS) may enhance cognition, to our knowledge, no study has directly assessed the effects of nVNS on brain function and cognitive performance in healthy individuals. The aim of this study was therefore to assess whether nVNS enhances complex visuospatial problem solving in a normative sample. Functional magnetic resonance imaging (fMRI) was used to examine underlying neural substrates.Material and methodsParticipants received transcutaneous cervical nVNS (N = 15) or sham (N = 15) stimulation during a 3 T fMRI scan. Stimulation lasted for 2 min at 24 V for nVNS and at 4.5 V for sham. Subjects completed a matrix reasoning (MR) task in the scanner and a forced-choice recognition task outside the scanner. An analysis of variance (ANOVA) was used to assess group differences in cognitive performance. And linear mixed effects (LMEs) regression analysis was used to assess main and interaction effects of experimental groups, level of MR task difficulty, and recall accuracy on changes in blood oxygen level-dependent (BOLD) signal.ResultsSubjects who received nVNS showed higher accuracy for both easy (p = 0.017) and hard (p = 0.013) items of the MR task, slower reaction times for hard items (p = 0.014), and fewer false negative errors during the forced-choice recognition task (p = 0.047). MR task difficulty related to increased activation in frontoparietal regions (p < 0.001). No difference between nVNS and sham stimulation was found on BOLD response during performance of the MR task.ConclusionsWe hypothesize that nVNS increased attention compared to sham, and that this effect led to enhanced executive functions, and consequently to better performance on visuospatial reasoning and recognition tasks. Results provide initial support that nVNS may be a low risk, low-cost treatment for cognitive disorders

Expansion of hippocampal and amygdala shape in posttraumatic stress and early life stress

Objective: The aim of this study was to examine the effect of Posttraumatic Stress Disorder (PTSD) and childhood adversity on brain structure. We assessed hippocampal and amygdala shape in veterans with varying levels of PTSD symptom severity and exposure to early life stressors (ELS). Methods: A total of 70 male veterans, who were deployed to a combat area during OIF/OEF/OND and who had been exposed to trauma during deployment, were included in the study. We applied a vertex-wise shape analysis of 3T MRI scans to measure indentation or expansion in hippocampal and amygdala shape. Results: Analyses showed a positive correlation between number of ELS and vertices in the right amygdala and the right hippocampus, as well as a positive correlation between PTSD symptom severity and right hippocampal vertices. There were no significant interactions between PTSD symptoms, ELS, and brain shape. Discussion: Results indicate a relationship between exposure to more childhood adversity and expansion in amygdala and hippocampal shape as well as between more severe PTSD symptoms and expansion in hippocampal shape. These findings may have important implications for the pathophysiology of trauma-related disorders

Episodic memory function is affected by lifestyle factors: a 14-year follow-up study in an elderly population

Understanding the relationship between memory function and lifestyle offers great opportunities for promoting beneficial lifestyle choices to foster healthy cognitive aging and for the development of intervention programs for older adults. We studied a cohort of older adults (age 65 and older) enrolled in the Longitudinal Aging Study Amsterdam, an ongoing prospective population-based research project. A total of 1,966 men and women participated in an episodic memory test every 3 years over a period of 14 years. Lifestyle habits were repeatedly assessed using self-report measures. Physical activity, light-to-moderate alcohol consumption, difficulties staying asleep, and social engagement were associated with better memory function over the course of 14 years. In contrast, smoking and long sleep duration were associated with worse memory function. These findings suggest that certain lifestyle factors can have long-term protective or harmful effects on memory function in aging individuals

Expansion of hippocampal and amygdala shape in posttraumatic stress and early life stress.

ObjectiveThe aim of this study was to examine the effect of Posttraumatic Stress Disorder (PTSD) and childhood adversity on brain structure. We assessed hippocampal and amygdala shape in veterans with varying levels of PTSD symptom severity and exposure to early life stressors (ELS).MethodsA total of 70 male veterans, who were deployed to a combat area during OIF/OEF/OND and who had been exposed to trauma during deployment, were included in the study. We applied a vertex-wise shape analysis of 3T MRI scans to measure indentation or expansion in hippocampal and amygdala shape.ResultsAnalyses showed a positive correlation between number of ELS and vertices in the right amygdala and the right hippocampus, as well as a positive correlation between PTSD symptom severity and right hippocampal vertices. There were no significant interactions between PTSD symptoms, ELS, and brain shape.DiscussionResults indicate a relationship between exposure to more childhood adversity and expansion in amygdala and hippocampal shape as well as between more severe PTSD symptoms and expansion in hippocampal shape. These findings may have important implications for the pathophysiology of trauma-related disorders

Non-invasive cervical vagus nerve stimulation effects on reaction time and valence image anticipation response

BackgroundNorepinephrine (NE) driven noninvasive vagus nerve stimulation (nVNS), which improves attention and reduces reaction time, augments learning. Equally important, endogenous NE mediated arousal is highly dependent on the valence (positive or negative) of the exogenous stimulus. But to date, no study has measured valence specific effects of nVNS on both functional magnetic resonance imaging (fMRI) anticipation task response and reaction time in healthy individuals. Therefore, the aim of this pilot study was to assess whether nVNS vs sham modulates valence cortical anticipation task response and reaction time in a normative sample.MethodsParticipants received right sided transcutaneous cervical nVNS (N = 12) or sham (N = 12) stimulation during a 3T fMRI scan. Subjects first performed a continuous performance task (CPT) and then a cued anticipation task to images of positively and negatively valenced events during fMRI. Reaction times to cues and Blood oxygen level dependent (BOLD) response were examined over phase to identify effects of nVNS/sham over time.ResultsnVNS reduced reaction time for all valenced image anticipation trials. With the fMRI anticipation task, we observed a valence-specific effect; nVNS increased responsivity to images with negative valence and decreased responsivity to images with positive valence, whereas sham showed an inverse valence response.ConclusionsnVNS was linked to reduced reaction time during the anticipation task. In tandem, nVNS consistently enhanced responsivity to negatively valenced images and diminished responsivity to positively valenced images, suggesting specific nVNS driven endogenous neurotransmitter signaling may contribute

Shared gray matter reductions across alcohol use disorder and posttraumatic stress disorder in the anterior cingulate cortex: A dual meta-analysis

The considerable comorbidity of posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) poses a greater public health burden than either condition alone. Although there is a substantial body of evidence linking the direct neurotoxic effect of heavy drinking to gray matter (GM) deficits, as well as a growing body of literature supporting a strong association between PTSD and GM alterations, there is scant research interrogating the direct interaction of the two disorders. In order to generate data-driven, specific hypotheses regarding the overlapping neural substrates of PTSD and AUD, we conducted a meta-analysis of GM volumes in each disorder relative to healthy control subjects. We found shared GM deficits in the anterior cingulate cortex (ACC) across both disorders relative to healthy control participants. These findings suggest that reduced volumes of the ACC across PTSD and AUD may have implications for the development, expression, or treatment of symptoms linked to these frequently co-existing disorders. Recommendations are made for future work aimed at delineating the specific and shared effects of traumatic stress and alcoholism on neural integrity