Differential impacts of healthy cognitive aging on directed and random exploration.

Deciding whether to explore unknown opportunities or exploit well-known options is a ubiquitous part of our everyday lives. Extensive work in college students suggests that young people make explore-exploit decisions using a mixture of information seeking and random behavioral variability. Whether, and to what extent, older adults use the same strategies is unknown. To address this question, 51 older adults (ages 65-74) and 32 younger adults (ages 18-25) completed the Horizon Task, a gambling task that quantifies information seeking and behavioral variability as well as how these strategies are controlled for the purposes of exploration. Qualitatively, we found that older adults performed similar to younger adults on this task, increasing both their information seeking and behavioral variability when it was adaptive to explore. Quantitively, however, there were substantial differences between the age groups, with older adults showing less information seeking overall and less reliance on variability as a means to explore. In addition, we found a subset of approximately 26% of older adults whose information seeking was close to zero, avoiding informative options even when they were clearly the better choice. Unsurprisingly, these "information avoiders" performed worse on the task. In contrast, task performance in the remaining "information seeking" older adults was comparable to that of younger adults suggesting that age-related differences in explore-exploit decision making may be adaptive except when they are taken to extremes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Exploring the potential of combining transcranial magnetic stimulation and electroencephalography to investigate mild cognitive impairment and Alzheimer's disease: a systematic review.

Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for investigating the complex mechanisms involved in age-related disorders, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). By systematically synthesizing TMS-EEG studies, this review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in clinical settings. PubMed, ScienceDirect, and PsychInfo were selected as the databases for this review. The 22 eligible studies included a total of 592 individuals with MCI or AD as well as 301 cognitively normal adults. TMS-EEG assessments unveiled specific patterns of corticospinal excitability, plasticity, and brain connectivity that distinguished individuals on the AD spectrum from cognitively normal older adults. Moreover, the TMS-induced EEG features were observed to be correlated with cognitive performance and the presence of AD pathological biomarkers. The comprehensive examination of the existing studies demonstrates that the combination of TMS and EEG has yielded valuable insights into the neurophysiology of MCI and AD. This integration shows great potential for early detection, monitoring disease progression, and anticipating response to treatment. Future research is of paramount importance to delve into the potential utilization of TMS-EEG for treatment optimization in individuals with MCI and AD.

Association Between Responsiveness to Transcranial Magnetic Stimulation and Interhemispheric Functional Connectivity of Sensorimotor Cortex in Older Adults.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic technique, and is believed to accomplish its effect by influencing the stimulated and remotely connected areas. However, responsiveness to rTMS shows high interindividual variability, and this intersubject variability is particularly high in older adults. It remains unclear whether baseline resting-state functional connectivity (rsFC) contributes to this variability in older adults. The aims of this study are to (1) examine rTMS effects over the primary motor cortex (M1) in older adults, and (2) identify baseline network properties that may contribute to the interindividual variability. Methods: We tested response to intermittent theta burst stimulation (iTBS), an effective rTMS protocol, over M1 by using both electromyography and resting-state functional magnetic resonance imaging in older adults. Outcome measures included motor-evoked potential (MEP) elicited by single-pulse transcranial magnetic stimulation and rsFC before and after an iTBS session. Results: iTBS significantly increased MEP amplitudes and rsFC between the stimulation site, sensorimotor cortex, and supplementary motor area (SMA) in older adults. iTBS-induced changes in MEP amplitude were positively correlated with increases in interhemispheric rsFC after iTBS. Furthermore, older adults with lower baseline interhemispheric rsFC between sensorimotor cortex and SMA exhibited stronger MEP response after iTBS. Discussion: Findings of the study suggest that different levels of interhemispheric communication during resting state might contribute to the response heterogeneity to iTBS in older adults. Interhemispheric rsFC may have great potential serving as a useful marker for predicting iTBS responsiveness in older adults. ClinicalTrials.gov ID: 1707654427 Impact statement Factors contributing to interindividual variability of the responsive to repetitive transcranial magnetic stimulation (rTMS) in older adults remain poorly understood. In this study, we examined the effects of rTMS over the primary motor cortex in older adults, and found that response to rTMS is associated with prestimulation interhemispheric connectivity in the sensorimotor and premotor areas. Findings of the study have great potential to be translated into a connectivity-based strategy for identification of responders for rTMS in older adults.

Opioid-induced microglia reactivity modulates opioid reward, analgesia, and behavior.

Opioid-induced microglia reactivity affects opioid reward and analgesic processes in ways that may contribute to the neurocognitive impairment observed in opioid addicted individuals. Opioids elicit microglia reactivity through the actions of opioid metabolites at TLR4 receptors, that are located primarily on microglia but are also present on astrocytes. Specifically, the M3G metabolite, which has no affinity for opioid receptors, exerts off-target effects on TLR4 receptors that can trigger downstream immunologic consequences. This off-target microglial reactivity, and the subsequent increase in microglial release of TNFα, IL-1ß, and BDNF, have been suggested to modulate both opioid-induced reward and opioid-induced analgesia. Despite occurring independently of each other, these neuro-immune effects could converge and result in overactivation of the insula. This would produce an imbalance between the "impulsive system" and the "executive system", such that the impulsive system's influence over behavior becomes dominant. This state, derived from changes in microglial reactivity, could contribute to impairment in a range of neurocognitive domains that are intricately involved in addiction and lead to increases in addiction-related behaviors.

Transcranial magnetic stimulation reveals diminished homoeostatic metaplasticity in cognitively impaired adults.

Homoeostatic metaplasticity is a neuroprotective physiological feature that counterbalances Hebbian forms of plasticity to prevent network destabilization and hyperexcitability. Recent animal models highlight dysfunctional homoeostatic metaplasticity in the pathogenesis of Alzheimer's disease. However, the association between homoeostatic metaplasticity and cognitive status has not been systematically characterized in either demented or non-demented human populations, and the potential value of homoeostatic metaplasticity as an early biomarker of cognitive impairment has not been explored in humans. Here, we report that, through pre-conditioning the synaptic activity prior to non-invasive brain stimulation, the association between homoeostatic metaplasticity and cognitive status could be established in a population of non-demented human subjects (older adults across cognitive spectrums; all within the non-demented range). All participants (n = 40; age range, 65-74, 47.5% female) underwent a standardized neuropsychological battery, magnetic resonance imaging and a transcranial magnetic stimulation protocol. Specifically, we sampled motor-evoked potentials with an input/output curve immediately before and after repetitive transcranial magnetic stimulation to assess neural plasticity with two experimental paradigms: one with voluntary muscle contraction (i.e. modulated synaptic activity history) to deliberately introduce homoeostatic interference, and one without to serve as a control condition. From comparing neuroplastic responses across these experimental paradigms and across cohorts grouped by cognitive status, we found that (i) homoeostatic metaplasticity is diminished in our cohort of cognitively impaired older adults and (ii) this neuroprotective feature remains intact in cognitively normal participants. This novel finding suggests that (i) future studies should expand their scope beyond just Hebbian forms of plasticity that are traditionally assessed when using non-invasive brain stimulation to investigate cognitive ageing and (ii) the potential value of homoeostatic metaplasticity in serving as a biomarker for cognitive impairment should be further explored.

Baseline Neurocognitive Performance and Symptoms in Those With Attention Deficit Hyperactivity Disorders and History of Concussion With Previous Loss of Consciousness.

Previous consensus statements on sports concussion have highlighted the importance of Attention Deficit Hyperactivity Disorder (ADHD) and loss of consciousness (LOC) as risk factors related to concussion management. The present study investigated how self-reported history of either ADHD diagnosis or history of previous concussion resulting in LOC influence baseline neurocognitive performance and self-reported symptoms. This analysis was performed retrospectively on data collected primarily from student-athletes, both Division 1 and club sports athletes. The dataset (n = 1460) is comprised of college students (age = 19.1 ± 1.4 years). Significant differences were found for composite scores on the ImPACT for both history of concussion (p = 0.016) and ADHD (p = 0.014). For concussion history, those with a previous concussion, non-LOC, performed better on the visual motor speed (p = 0.004). Those with diagnosis of ADHD performed worse on verbal memory (p = 0.001) and visual motor speed (p = 0.033). For total symptoms, concussion history (p < 0.001) and ADHD (p = 0.001) had an influence on total symptoms. Those with ADHD reported more symptoms for concussion history; those with previous LOC concussion reported more symptoms than those with non-LOC concussion (p = 0.003) and no history (p < 0.001). These results highlight the importance of baseline measures of neurocognitive function and symptoms in concussion management in order to account for pre-existing conditions such as ADHD and LOC from previous concussion that could influence these measures.

Genetics Influence Neurocognitive Performance at Baseline but Not Concussion History in Collegiate Student-Athletes.

OBJECTIVE: This study investigates 4 single-nucleotide polymorphisms [Apolipoprotein E (APOE), APOE promoter, catechol-O-methyl transferase (COMT), and dopamine D2 receptor] that have been implicated in concussion susceptibility and/or cognitive ability in collegiate student-athletes. DESIGN: Cross-sectional study. SETTING: Neuroscience laboratory at Elon University. PARTICIPANTS: Two hundred fifty division I collegiate student-athletes (66 women, 184 men) from various sports. INTERVENTION: All participants completed Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) testing at baseline concussion testing and had a buccal swab taken for DNA for genotyping. MAIN OUTCOME MEASURES: Self-reported history of concussions and neurocognitive performance were taken from ImPACT. RESULTS: Individuals carrying an ε4 allele in their APOE gene had a significantly slower reaction time (P = 0.001). Individuals homozygous for the Val allele of the COMT gene showed significantly worse impulse control scores (P = 0.014). None of the genotypes were able to predict self-reported concussion history in collegiate student-athletes. CONCLUSIONS: These results indicate that certain genotypes may influence performance on cognitive testing at baseline and that the APOE genotypes may not influence concussion susceptibility as suggested by past studies.

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease.

As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

Neuroimaging of Parkinson's disease: Expanding views.

Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson's disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD.

Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques.

Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.