Evaluating denoising strategies in resting-state functional magnetic resonance in traumatic brain injury (EpiBioS4Rx).

Resting-state functional MRI is increasingly used in the clinical setting and is now included in some diagnostic guidelines for severe brain injury patients. However, to ensure high-quality data, one should mitigate fMRI-related noise typical of this population. Therefore, we aimed to evaluate the ability of different preprocessing strategies to mitigate noise-related signal (i.e., in-scanner movement and physiological noise) in functional connectivity (FC) of traumatic brain injury (TBI) patients. We applied nine commonly used denoising strategies, combined into 17 pipelines, to 88 TBI patients from the Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy clinical trial. Pipelines were evaluated by three quality control (QC) metrics across three exclusion regimes based on the participant's head movement profile. While no pipeline eliminated noise effects on FC, some pipelines exhibited relatively high effectiveness depending on the exclusion regime. Once high-motion participants were excluded, the choice of denoising pipeline becomes secondary - although this strategy leads to substantial data loss. Pipelines combining spike regression with physiological regressors were the best performers, whereas pipelines that used automated data-driven methods performed comparatively worse. In this study, we report the first large-scale evaluation of denoising pipelines aimed at reducing noise-related FC in a clinical population known to be highly susceptible to in-scanner motion and significant anatomical abnormalities. If resting-state functional magnetic resonance is to be a successful clinical technique, it is crucial that procedures mitigating the effect of noise be systematically evaluated in the most challenging populations, such as TBI datasets.

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.

BACKGROUND: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). METHODS: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. RESULTS: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. LIMITATIONS: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. CONCLUSION: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

Carotid stenting versus endarterectomy cognitive outcomes.

BACKGROUND: The objectives are to analyze the impact of carotid revascularization on cognitive performance after a 3-month period in patients, who have undergone carotid artery stenting (CAS) or carotid endarterectomy (CEA), and to compare the cognitive outcomes between these 2 groups of patients. This a nonrandomized and prospective single-center experience. METHODS: This study was performed in the University of Campinas Hospital from January 2010 to January 2012 and included 30 patients with carotid stenosis who received carotid interventions. Nineteen patients received CEA and 11 patients received CAS. Neuropsychologic evaluation included general cognitive, language, visuospatial, attentional, executive function, and memory tests. RESULTS: After the follow-up period, there was improvement in episodic memory, encoding subitem (P = 0.02), and delayed recall (P = 0.02) for the CEA group. The CAS group improved in episodic memory, encoding subitem (P = 0.009), working memory (P = 0.04), and executive functions (P = 0.02). Comparing the techniques, the CAS group showed higher scores only in executive functions (P = 0.02). CONCLUSIONS: Both groups had a similar performance in cognitive tests, comparing preoperative and postoperative results. However, patients who underwent CAS tended to achieve higher scores in executive function and operational memory/attention tests.

Cognitive styles and psi: psi researchers are more similar to skeptics than to lay believers.

Introduction: Belief in psi, which includes psychic phenomena such as extra-sensory perception and post-mortem survival, is widespread yet controversial. According to one of the leading and perhaps most tested hypotheses, high belief in psi can be explained by differences in various aspects of cognition, including cognitive styles. Most of this research has been conducted with lay individuals. Here, we tested the hypothesis that academic researchers who investigate psi may exhibit different cognitive styles than lay individuals interested in psi, and are more similar to skeptics. Methods: We measured two cognitive styles-actively open-minded thinking (AOT) and the need for closure (NFC)-and assessed differences among four heterogeneous groups regarding belief in psi and involvement in related research. Specifically, our study included academic psi researchers (N = 44), lay individuals who believe in psi (N = 32), academics who are skeptics of psi (N = 35), and lay individuals who are skeptics (N = 33). Results: We found group differences in AOT (p = 0.003) but not in NFC scores (p = 0.67). Post hoc tests showed no significant difference in AOT scores between academics who conduct psi research (4.5 ± 0.3) and academic skeptics (4.5 ± 0.3; p = 0.91) or lay skeptics (4.5 ± 0.4; p = 0.80). The lay psi group had significantly lower AOT scores (4.2 ± 0.4) than the other three groups (ps: 0.005-0.04), indicating a decreased willingness to consider a range of evidence when forming an opinion, including evidence that challenges their beliefs. AOT was negatively associated with psi belief in the two skeptic groups combined (r = -0.29, p = 0.01), but not in the psi groups (r = -0.03, p = 0.78). Discussion: Our research shows that academics who work with psi differ from lay psi individuals, but not from skeptics, in actively open-minded thinking. In other words, despite their high belief in psi phenomena, psi researchers demonstrate a commitment to sound reasoning about evidence that is no different from that of skeptics.

Exploring the transformative potential of out-of-body experiences: A pathway to enhanced empathy.

Out-of-body experiences (OBEs) are subjective phenomena during which individuals feel disembodied or perceive themselves as outside of their physical bodies, often resulting in profound and transformative effects. In particular, experiencers report greater heightened pro-social behavior, including more peaceful relationships, tolerance, and empathy. Drawing parallels with the phenomenon of ego dissolution induced by certain psychedelic substances, we explore the notion that OBEs may engender these changes through ego dissolution, which fosters a deep-seated sense of unity and interconnectedness with others. We then assess potential brain mechanisms underlying the link between OBEs and empathy, considering the involvement of the temporoparietal junction and the Default Mode Network. This manuscript offers an examination of the potential pathways through which OBEs catalyze empathic enhancement, shedding light on the intricate interplay between altered states of consciousness and human empathy.

Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation.

Introduction: Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that uses pulsed magnetic fields to affect the physiology of the brain and central nervous system. Repetitive TMS (rTMS) has been used to study and treat several neurological conditions, but its complex molecular basis is largely unexplored. Methods: Utilizing three experimental rat models (in vitro, ex vivo, and in vivo) and employing genome-wide microarray analysis, our study reveals the extensive impact of rTMS treatment on gene expression patterns. Results: These effects are observed across various stimulation protocols, in diverse tissues, and are influenced by time and age. Notably, rTMS-induced alterations in gene expression span a wide range of biological pathways, such as glutamatergic, GABAergic, and anti-inflammatory pathways, ion channels, myelination, mitochondrial energetics, multiple neuron-and synapse-specific genes. Discussion: This comprehensive transcriptional analysis induced by rTMS stimulation serves as a foundational characterization for subsequent experimental investigations and the exploration of potential clinical applications.

Volumetric brain changes in thalamus, corpus callosum and medial temporal structures: mild Alzheimer's disease compared with amnestic mild cognitive impairment.

BACKGROUND: It is widely known that atrophy of medial temporal structures is present in the mild stage of Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, structures such as the thalamus and corpus callosum are much less studied. METHODS: We compared the volumes of the entorhinal cortex, hippocampus, thalamus and the corpus callosum in 14 controls, 14 patients with mild AD and 15 with aMCI and correlated these volumes with neuropsychological data. MRI was obtained at 2 T followed by manual segmentation. RESULTS: We found atrophy in hippocampi and thalami of MCI patients compared to controls, and in the bilateral entorhinal cortex of aMCI compared to AD patients. All the structures showed atrophy in AD patients compared to controls, including the corpus callosum. CONCLUSIONS: Our study confirms that thalamic areas are atrophied in aMCI, and the corpus callosum might represent a good structural marker for mild AD. Those areas were associated with cognitive functions already described in the literature.

Effects of repetitive Transcranial Magnetic Stimulation in aged rats depend on pre-treatment cognitive status: Toward individualized intervention for successful cognitive aging.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) has shown initial promise in combating age-related cognitive decline and dementia. The nature and severity of cognitive aging, however, varies markedly between individuals. OBJECTIVE/HYPOTHESIS: We hypothesized that the distinct constellation of brain changes responsible for individual differences in cognitive aging might influence the response to rTMS. METHODS: Cognitive effects of rTMS were evaluated using a rat model of cognitive aging in which aged rats are classified as Aged-Impaired (AI) or -Unimpaired (AU) relative to young (Y) according to their performance in the Morris water maze. Several weeks later, following presentation of a sample odor in an olfactory recognition task, rats received either sham (Y, n = 9; AU, n = 8; AI, n = 9) or intermittent Theta Burst Stimulation (Y, n = 8; AU, n = 8; AI, n = 9). Memory was tested 24 h later. RESULTS: Recognition memory in the sham and stimulated conditions depended on pre-treatment cognitive status in the aged rats. Y and AU sham rats displayed robust odor recognition, whereas sham-treated AI rats exhibited no retention. In contrast, rTMS treated AI rats showed robust retention, comparable in magnitude to Y, whereas the AU stimulated scored at chance. CONCLUSION: Our results are consistent with a perspective that the unique neurobiology associated with variability in cognitive aging modulates the response to rTMS. Protocols with documented efficacy in young adults may have unexpected outcomes in aging or neurodegenerative conditions, requiring individualized approaches.

Subacute functional connectivity correlates with cognitive recovery six months after stroke.

BACKGROUND AND PURPOSE: Cognitive impairment is a common consequence of stroke, and the rewiring of the surviving brain circuits might contribute to cognitive recovery. Studies investigating how the functional connectivity of networks change across time and whether their remapping relates to cognitive recovery in stroke patients are scarce. We aimed to investigate whether resting-state functional connectivity was associated with cognitive performance in stroke patients and if any alterations in these networks were correlated with cognitive recovery. METHODS: Using an fMRI ROI-ROI approach, we compared the ipsilesional, contralesional and interhemispheric functional connectivity of three resting-state networks involved in cognition - the Default Mode (DMN), Salience (SN) and Central Executive Networks (CEN), in subacute ischemic stroke patients (time 1, n = 37, stroke onset: 24.32 ± 7.44 days, NIHSS: 2.66 ± 3.45) with cognitively healthy controls (n = 20). Patients were reassessed six months after the stroke event (time 2, n = 20, stroke onset: 182.05 ± 8.17 days) to verify the subsequent reorganization of functional connections and whether such reorganization was associated with cognitive recovery. RESULTS: At time 1, patients had weaker interhemispheric connectivity in the DMN than controls; better cognitive performance at time 1 was associated with stronger interhemispheric and ipsilesional DMN connectivity, and weaker contralesional SN connectivity. At time 2, there were no changes in functional connectivity in stroke patients, compared to time 1. Better cognitive recovery measured at time 2 (time 2 - time 1) was associated with stronger functional connectivity in the DMN, and weaker interhemispheric subacute connectivity in the SN, both from time 1. CONCLUSIONS: Stroke disrupts the functional connectivity of the DMN, not only at the lesioned hemisphere but also between hemispheres. Six months after the stroke event, we could not detect the remapping of networks. Cognitive recovery was associated with the connectivity of both the DMN and SN of time 1. Our findings may be helpful for facilitating further understanding of the potential mechanisms underlying post-stroke cognitive performance.

Transcranial Magnetic Stimulation in Alzheimer's Disease: Are We Ready?

Transcranial magnetic stimulation (TMS) is among a growing family of noninvasive brain stimulation techniques being developed to treat multiple neurocognitive disorders, including Alzheimer's disease (AD). Although small clinical trials in AD have reported positive effects on cognitive outcome measures, significant knowledge gaps remain, and little attention has been directed at examining the potential influence of TMS on AD pathogenesis. Our review briefly outlines some of the proposed neurobiological mechanisms of TMS benefits in AD, with particular emphasis on the modulatory effects on excitatory/inhibitory balance. On the basis of converging evidence from multiple fields, we caution that TMS therapeutic protocols established in young adults may have unexpected detrimental effects in older individuals or in the brain compromised by AD pathology. Our review surveys clinical studies of TMS in AD alongside basic research as a guide for moving this important area of work forward toward effective treatment development.