Repetitive Transcranial Magnetic Stimulation (rTMS) in Mild Cognitive Impairment: Effects on Cognitive Functions-A Systematic Review.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique also used as a non-pharmacological intervention against cognitive impairment. The purpose of the present review was to summarize what is currently known about the effectiveness of rTMS intervention on different cognitive domains in patients with mild cognitive impairment (MCI) and to address potential neuromodulation approaches in combination with electroencephalography (EEG) and neuroimaging, especially functional magnetic resonance imaging (fMRI). In this systematic review, we consulted three main databases (PubMed, Science Direct, and Scopus), and Google Scholar was selected for the gray literature search. The PRISMA flowchart drove the studies' inclusion. The selection process ensured that only high-quality studies were included; after removing duplicate papers, explicit ratings were given based on the quality classification as high (A), moderate (B), or low (C), considering factors such as risks of bias, inaccuracies, inconsistencies, lack of direction, and publication bias. Seven full-text articles fulfilled the stated inclusion, reporting five double-blind, randomized, sham-controlled studies, a case study, and a randomized crossover trial. The results of the reviewed studies suggested that rTMS in MCI patients is safe and effective for enhancing cognitive functions, thus making it a potential therapeutic approach for MCI patients. Changes in functional connectivity within the default mode network (DMN) after targeted rTMS could represent a valuable indicator of treatment response. Finally, high-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has been shown to significantly enhance cognitive functions, such as executive performance, together with the increase of functional connectivity within frontoparietal networks. The main limitations were the number of included studies and the exclusion of studies using intermittent theta-burst stimulation, used in studies on Alzheimer's disease. Therefore, neuroimaging techniques in combination with rTMS have been shown to be useful for future network-based, fMRI-guided therapeutic approaches.

Cognitive, behavioral, and brain functional connectivity correlates of fatigue in amyotrophic lateral sclerosis.

INTRODUCTION: Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS). We aim at investigating the clinical correlations between "physical" and "mental" components of fatigue, measured by the Multidimensional Fatigue Inventory scale, and motor and cognitive/behavioral disability in a large sample of patients with ALS. We also investigated the correlations between these measures of fatigue and resting-state functional connectivity of brain functional magnetic resonance imaging (RS-fMRI) large-scale networks in a subset of patients. METHODS: One hundred and thirty ALS patients were assessed for motor disability, cognitive and behavioral dysfunctions, fatigue, anxiety, apathy, and daytime sleepiness. Moreover, the collected clinical parameters were correlated with RS-fMRI functional connectivity changes in the large-scale brain networks of 30 ALS patients who underwent MRI. RESULTS: Multivariate correlation analysis revealed that "physical" fatigue was related to anxiety and respiratory dysfunction, while "mental" fatigue was related to memory impairment and apathy. Moreover, the mental fatigue score was directly related to functional connectivity in the right and left insula (within the salience network), and inversely related to functional connectivity in the left middle temporal gyrus (within the default mode network). CONCLUSIONS: Although the "physical" component of fatigue may be influenced by the disease itself, in ALS the "mental" component of fatigue correlates with cognitive and behavioral impairment, as well as with alterations of functional connectivity in extra-motor networks.

Long-Term Neuromodulatory Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Plasmatic Matrix Metalloproteinases (MMPs) Levels and Visuospatial Abilities in Mild Cognitive Impairment (MCI).

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia.

Resting state fMRI analysis of pseudobulbar affect in Amyotrophic Lateral Sclerosis (ALS): motor dysfunction of emotional expression.

Pseudobulbar affect (PBA), referring to exaggerated or inappropriate episodes of laughing and/or crying without an apparent motivating stimulus, has been mainly attributed to bilateral degeneration of corticobulbar tracts. We aimed at exploring brain functional connectivity (FC) correlates of PBA in patients with amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, frequently associated with PBA. Resting state functional MRI (RS-fMRI) independent component (ICA) and seed-based analyses and voxel-based morphometry (VBM) whole-brain analysis were performed on 27 ALS patients (13 with PBA; 14 without PBA) and 26 healthy controls (HC), for investigating functional and structural abnormalities in ALS patients compared to HC and in patients with PBA compared to patients without PBA. Between-patient analysis revealed different FC patterns, especially regarding decreased FC in several areas of cognitive (default mode, frontoparietal, salience) and sensory-motor networks in patients with PBA compared to those without PBA. However, no significant differences were found in gray matter atrophy. Seed-based analysis showed increased FC between middle cerebellar peduncles and posterior cingulate cortex and decreased FC between middle cerebellar peduncles and left middle frontal gyrus in patients with PBA compared to patients without PBA. Our findings suggest that some alterations of fronto-tempo-parietal-cerebellar circuits could be related to PBA in ALS. In particular, the abnormal FC between cerebellum and posterior cingulate cortex and left middle frontal gyrus in patients with PBA compared to patients without PBA highlights a crucial role of the cerebellum in regulating emotion expression in patients with ALS.

Psychological Support for Family Caregivers of Patients With Amyotrophic Lateral Sclerosis at the Time of the Coronavirus Disease 2019 Pandemic: A Pilot Study Using a Telemedicine Approach.

The coronavirus disease 2019 (COVID-19) pandemic confined most of the population to homes worldwide, and then, a lot of amyotrophic lateral sclerosis (ALS) centers moved to telemedicine services to continue to assist both patients with ALS and their caregivers. This pilot, randomized, controlled study aimed to explore the potential role of psychological support interventions for family caregivers of patients with ALS through resilience-oriented sessions of group therapy during the COVID-19 pandemic. In total, 12 caregivers agreed to be remotely monitored by our center since March 2020 and underwent scales for global burden (i.e., Caregiver Burden Inventory, CBI), resilience (i.e., Connor Davidson Resilience Scale, CD-RISC), and perceived stress (i.e., Perceived Stress Scale, PSS) at two-time points (i.e., at pre-treatment assessment and after 9 months or at post-treatment assessment). They were randomized into two groups: the former group underwent resilience-oriented sessions of group therapy two times a month for 3 months, while the latter one was only remotely monitored. No significant differences were found in CBI, CD-RISC, and PSS during the 9-month observation period in the treated group compared with the control group, suggesting a trend toward stability of caregiver burden together with resilience and perceived stress scores in all the subjects monitored. The lack of differences in caregivers' burden, resilience, and perceived stress scores by comparing the two groups monitored during 9 months could be due to the co-occurrence of the COVID-19 pandemic with the stressful events related to caring for patients with ALS that might have hindered the detection of significant benefits from short-lasting psychological support.

Integrated Cognitive Rehabilitation Home-Based Protocol to Improve Cognitive Functions in Multiple Sclerosis Patients: A Randomized Controlled Study.

Cognitive impairment (CI) occurs in about 40-65% of people with multiple sclerosis (MS) during the disease course. Cognitive rehabilitation has produced non-univocal results in MS patients. OBJECTIVE: The present study aimed to evaluate whether an Integrated Cognitive Rehabilitation Program (ICRP) in MS patients might significantly improve CI. METHODS: Forty patients with three phenotypes of MS were randomly assigned into two groups: the experimental group (EG, n = 20), which participated in the ICRP for 10 weeks of training; and the control group (CG, n = 20). All participants' cognitive functions were assessed at three timepoints (baseline, post-treatment, and 3-month follow-up) with the California Verbal Learning (CVLT), Brief Visuospatial Memory (BVMTR), Numerical Stroop, and Wisconsin tests. RESULTS: When compared to CG patients, EG patients showed significant improvements in several measures of cognitive performance after ICRP, including verbal learning, visuospatial memory, attention, and executive functions. CONCLUSIONS: Home-based ICRP can improve cognitive functions and prevent the deterioration of patients' cognitive deficits. As an integrated cognitive rehabilitation program aimed at potentiation of restorative and compensatory mechanisms, this approach might suggest an effective role in preserving neuronal flexibility as well as limiting the progression of cognitive dysfunction in MS.

Traumatic brain injury (TBI): exploring degrees and causes of TBI in mental health impairment by comprising gender differences / Traumatismo cranioencefálico (TCE): explorando graus e causas do TCE e comprometimento da saúde mental por compreender gênero

ABSTRACT Objective: To exploring differences between degrees and causes of TBI in mental health impairment with comprising gender differences. Methods: The study was a cross-sectional observational study of TBI patients who bedded within 24 hours of presentation to the emergency department (ED), Khatam Hospital, located in Zahedan, Iran. Participants were randomized by a simple randomization technique. Information had been collected twice, first time screening patients by Glasgow Coma Scale score (GCS) and the second time was two months after discharging patients from the ED to estimate mental health impairment by using two separate clinical diagnostic tests. Results: The research considered 80 patients, with 66% being male and 34% female. The median age for both genders estimated 23.5 years. There was a statistically significant difference between degrees and causes of TBI on the total score of hospital anxiety and depression. In particular, degree and cause of TBI with depression in males (M = 14.54, SD = .22), and degrees of TBI on post-traumatic stress disorder in females (M = 87, SD = .7) were significant difference. Conclusion: The current investigation highlights the incidence of depression in male patients with severe levels of traumatic brain injury who injured by car accident multiple trauma; furthermore, this research found the remarkable rate of post-traumatic stress disorder in female patients with a mild degree of TBI. The researcher in traumatic brain injury should seriously deliberate and explore gender differences with the degree and cause of TBI in detail.

RESUMO Objetivo: Explorar diferenças entre graus e causas de traumatismo cranioencefálico (TCE) no comprometimento de saúde mental de acordo com o gênero. Métodos: Estudo observacional transversal de pacientes com TCE que se hospitalizaram dentro de 24 horas após a apresentação no pronto-socorro (PS) no Hospital Khatam, localizado em Zahedan, Irã. Os participantes foram randomizados e as informações foram coletadas duas vezes: na primeira vez, na triagem, os pacientes foram avaliados pela Escala de Coma de Glasgow (GCS); na segunda vez, dois meses depois da alta do PS, eles foram avaliados para estimar o comprometimento da saúde mental usando dois instrumentos de avaliação independentes. Resultados: A amostra foi constituída de 80 pacientes, 66% sendo do sexo masculino e 34% do sexo feminino. A idade mediana para ambos os sexos estimada foi de 23,5 anos. Houve uma diferença estatisticamente significativa entre graus e causas de TCE no escore total de ansiedade hospitalar e depressão. Em particular, o grau e a causa de TCE estiveram associados com depressão no sexo masculino (M = 14,54, DS = 0,22) e os graus de TCE, com transtorno de estresse pós-traumático em mulheres (M = 87, DS = 0,7). Conclusão: Este estudo destaca a incidência de depressão em pacientes do sexo masculino com níveis graves de lesão cerebral traumática e que se feriram por acidente de carro com trauma múltiplo; além disso, observamos uma notável taxa de transtorno de estresse pós-traumático em pacientes do sexo feminino com um grau leve de TCE. O pesquisador em lesão cerebral traumática deve explorar séria e detalhadamente as diferenças de gênero com o grau e a causa do TCE.

Impacts of cognitive impairment for different levels and causes of traumatic brain injury, and education status in TBI patients.

Traumatic brain injury (TBI) is one of main causes of death and disability among many young and old populations in different countries. OBJECTIVE: The aim of this study were to consider and predict the cognitive impairments according to different levels and causes of TBI, and education status. METHODS: The study was performed using the Mini-Mental State Examination (MMSE) to estimate cognitive impairment in patients at a trauma center in Zahedan city. Individuals were considered eligible if 18 years of age or older. This investigation assessed a subset of patients from a 6-month pilot study. RESULTS: The study participants comprised 66% males and 34% females. Patient mean age was 32.5 years and SD was 12.924 years. One-way analysis of variance between groups indicated cognitive impairment related to different levels and causes of TBI, and education status in patients. There was a significant difference in the dimensions of cognitive impairments for different levels and causes of TBI, and education status. A regression test showed that levels of traumatic brain injury (b=.615, p=.001) and education status (b=.426, p=.001) predicted cognitive impairment. CONCLUSION: Different levels of TBI and education status were useful for predicting cognitive impairment in patients. Severe TBI and no education were associated with worse cognitive performance and higher disability. These data are essential in terms of helping patients understand their needs. Therefore, the factors identified can help plan effective rehabilitation programs.

A lesão cerebral traumática (TCE) é uma das principais causas de morte e incapacidade em muitos jovens e idosos em diferentes países. OBJETIVO: O objetivo deste estudo foi considerar e prever os prejuízos cognitivos para os diferentes níveis e causas do TCE e status de educação. MÉTODOS: O estudo foi feito usando o Mini-Exame do Estado Mental (MMSE) para estimar o comprometimento cognitivo em pacientes dirigido a um centro de trauma na cidade de Zahedan. Os indivíduos foram considerados elegíveis se tivessem 18 anos de idade ou mais. Esta investigação avaliou um subconjunto de pacientes de um estudo piloto de 6 meses. RESULTADOS: Os participantes do estudo foram 66% do sexo masculino e 34% do sexo feminino. A média de idade dos pacientes foi de 32,5 anos e DP foi de 12,924 anos. A análise de variância unidirecional entre grupos indicou comprometimento cognitivo relacionado a diferentes níveis e causas de TCE e status de educação em pacientes. Houve uma diferença significativa nas dimensões de deficiências cognitivas para os diferentes níveis e causas de TCE e status de educação. O teste de regressão mostrou que níveis de lesão cerebral traumática (b=0,615, p=0,001) e o status de educação (b=0,426, p=0,001) predizem o comprometimento cognitivo. CONCLUSÃO: Os diferentes níveis de TCE e estados de educação foram uteis para prever o comprometimento cognitivo em pacientes. TCE grave e sem educação foram relacionadas a piora do desempenho cognitivo e maior incapacidade. Esses dados são essenciais para ajudar os pacientes a entender o que realmente precisam, portanto, os fatores identificados podem contribuir no planejamento de programas de reabilitação efetivos.

Impacts of cognitive impairment for different levels and causes of traumatic brain injury, and education status in TBI patients / Impactos do comprometimento cognitivo para diferentes níveis e causas de traumatismo cranioencefálico e grau de instrução em pacientes lesados

ABSTRACT Traumatic brain injury (TBI) is one of main causes of death and disability among many young and old populations in different countries. Objective: The aim of this study were to consider and predict the cognitive impairments according to different levels and causes of TBI, and education status. Methods: The study was performed using the Mini-Mental State Examination (MMSE) to estimate cognitive impairment in patients at a trauma center in Zahedan city. Individuals were considered eligible if 18 years of age or older. This investigation assessed a subset of patients from a 6-month pilot study. Results: The study participants comprised 66% males and 34% females. Patient mean age was 32.5 years and SD was 12.924 years. One-way analysis of variance between groups indicated cognitive impairment related to different levels and causes of TBI, and education status in patients. There was a significant difference in the dimensions of cognitive impairments for different levels and causes of TBI, and education status. A regression test showed that levels of traumatic brain injury (b=.615, p=.001) and education status (b=.426, p=.001) predicted cognitive impairment. Conclusion: Different levels of TBI and education status were useful for predicting cognitive impairment in patients. Severe TBI and no education were associated with worse cognitive performance and higher disability. These data are essential in terms of helping patients understand their needs. Therefore, the factors identified can help plan effective rehabilitation programs.

RESUMO A lesão cerebral traumática (TCE) é uma das principais causas de morte e incapacidade em muitos jovens e idosos em diferentes países. Objetivo: O objetivo deste estudo foi considerar e prever os prejuízos cognitivos para os diferentes níveis e causas do TCE e status de educação. Métodos: O estudo foi feito usando o Mini-Exame do Estado Mental (MMSE) para estimar o comprometimento cognitivo em pacientes dirigido a um centro de trauma na cidade de Zahedan. Os indivíduos foram considerados elegíveis se tivessem 18 anos de idade ou mais. Esta investigação avaliou um subconjunto de pacientes de um estudo piloto de 6 meses. Resultados: Os participantes do estudo foram 66% do sexo masculino e 34% do sexo feminino. A média de idade dos pacientes foi de 32,5 anos e DP foi de 12,924 anos. A análise de variância unidirecional entre grupos indicou comprometimento cognitivo relacionado a diferentes níveis e causas de TCE e status de educação em pacientes. Houve uma diferença significativa nas dimensões de deficiências cognitivas para os diferentes níveis e causas de TCE e status de educação. O teste de regressão mostrou que níveis de lesão cerebral traumática (b=0,615, p=0,001) e o status de educação (b=0,426, p=0,001) predizem o comprometimento cognitivo. Conclusão: Os diferentes níveis de TCE e estados de educação foram uteis para prever o comprometimento cognitivo em pacientes. TCE grave e sem educação foram relacionadas a piora do desempenho cognitivo e maior incapacidade. Esses dados são essenciais para ajudar os pacientes a entender o que realmente precisam, portanto, os fatores identificados podem contribuir no planejamento de programas de reabilitação efetivos.