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Previous research has examined resting electroencephalographic (EEG) data to explore brain activity related to meditation. However, previous research has mostly examined power in different frequency bands. The practical objective of this study was to comprehensively test whether other types of time-series analysis methods are better suited to characterize brain activity related to meditation. To achieve this, we compared >7000 time-series features of the EEG signal to comprehensively characterize brain activity differences in meditators, using many measures that are novel in meditation research. Eyes-closed resting-state EEG data from 49 meditators and 46 non-meditators was decomposed into the top eight principal components (PCs). We extracted 7381 time-series features from each PC and each participant and used them to train classification algorithms to identify meditators. Highly differentiating individual features from successful classifiers were analysed in detail. Only the third PC (which had a central-parietal maximum) showed above-chance classification accuracy (67 %, pFDR = 0.007), for which 405 features significantly distinguished meditators (all pFDR < 0.05). Top-performing features indicated that meditators exhibited more consistent statistical properties across shorter subsegments of their EEG time-series (higher stationarity) and displayed an altered distributional shape of values about the mean. By contrast, classifiers trained with traditional band-power measures did not distinguish the groups (pFDR > 0.05). Our novel analysis approach suggests the key signatures of meditators' brain activity are higher temporal stability and a distribution of time-series values suggestive of longer, larger, or more frequent non-outlying voltage deviations from the mean within the third PC of their EEG data. The higher temporal stability observed in this EEG component might underpin the higher attentional stability associated with meditation. The novel time-series properties identified here have considerable potential for future exploration in meditation research and the analysis of neural dynamics more broadly.
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Meditação , Humanos , Encéfalo , Eletroencefalografia , Atenção , DescansoRESUMO
OBJECTIVE: The objective of this study was to investigate clinical symptoms, cognitive performance and cortical activity following mild traumatic brain injury (mTBI). METHODS: We recruited 30 individuals in the sub-acute phase post mTBI and 28 healthy controls with no history of head injury and compared these groups on clinical, cognitive and cortical activity measures. Measures of cortical activity included; resting state electroencephalography (EEG), task related EEG and combined transcranial magnetic stimulation with electroencephalography (TMS-EEG). Primary analyses investigated clinical, cognitive and cortical activity differences between groups. Exploratory analyses investigated the relationships between these measures. RESULTS: At 4 weeks' post injury, mTBI participants exhibited significantly greater post concussive and clinical symptoms compared to controls; as well as reduced cognitive performance on verbal learning and working memory measures. mTBI participants demonstrated alterations in cortical activity while at rest and in response to stimulation with TMS. CONCLUSIONS: The present study comprehensively characterized the multidimensional effect of mTBI in the sub-acute phase post injury, showing a broad range of differences compared to non-mTBI participants. Further research is needed to explore the relationship between these pathophysiologies and clinical/cognitive symptoms in mTBI.
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Electroencephalographic (EEG) microstates can provide a unique window into the temporal dynamics of large-scale brain networks across brief (millisecond) timescales. Here, we analysed fundamental temporal features of microstates extracted from the broadband EEG signal in a large (N = 139) cohort of children spanning early-to-middle childhood (4-12 years of age). Linear regression models were used to examine if participants' age and biological sex could predict the temporal parameters GEV, duration, coverage, and occurrence, for five microstate classes (A-E) across both eyes-closed and eyes-open resting-state recordings. We further explored associations between these microstate parameters and posterior alpha power after removal of the 1/f-like aperiodic signal. The microstates obtained from our neurodevelopmental EEG recordings broadly replicated the four canonical microstate classes (A to D) frequently reported in adults, with the addition of the more recently established microstate class E. Biological sex served as a significant predictor in the regression models for four of the five microstate classes (A, C, D, and E). In addition, duration and occurrence for microstate E were both found to be positively associated with age for the eyes-open recordings, while the temporal parameters of microstates C and E both exhibited associations with alpha band spectral power. Together, these findings highlight the influence of age and sex on large-scale functional brain networks during early-to-middle childhood, extending understanding of neural dynamics across this important period for brain development.
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Encéfalo , Eletroencefalografia , Adulto , Humanos , Criança , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Olho , Modelos LinearesRESUMO
There is growing evidence that neural network dysfunction is a likely proximate cause of cognitive impairment in Alzheimer's disease and may represent a promising therapeutic target. Here, we investigated whether a course of intermittent theta burst stimulation (iTBS) could modulate functional connectivity and cognition in mild to moderate Alzheimer's. In a double-blind parallel randomized sham-controlled trial, 58 participants were randomized to either active or sham iTBS. Stimulation was applied to the left dorsolateral prefrontal cortex, right dorsolateral prefrontal cortex, left posterior parietal cortex, and right posterior parietal cortex in every treatment session. Neurobiological (electroencephalography), cognitive, and behavioral functional assessments were undertaken at baseline and end of treatment. Cognitive and functional assessments were also conducted at 3 (blinded) and 6 month (active group only) follow-ups. Active iTBS increased resting-state gamma connectivity and improved delayed recall on an episodic memory task. Both baseline gamma connectivity and change in gamma connectivity predicted improved delayed recall following active treatment. These findings support future research into iTBS for Alzheimer's focusing on protocol optimization.
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Doença de Alzheimer , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Eletroencefalografia , Lobo Parietal , Método Duplo-Cego , Córtex Pré-Frontal/fisiologiaRESUMO
OBJECTIVE: To find sensitive neurophysiological correlates of non-motor symptoms in Huntington's disease (HD), which are essential for the development and assessment of novel treatments. METHODS: We used resting state EEG to examine differences in oscillatory activity (analysing the isolated periodic as well as the complete EEG signal) and functional connectivity in 22 late premanifest and early stage people with HD and 20 neurotypical controls. We then assessed the correlations between these neurophysiological markers and clinical measures of apathy and processing speed. RESULTS: Significantly lower theta and greater delta resting state power was seen in the HD group, as well as significantly greater delta connectivity. There was a significant positive correlation between theta power and processing speed, however there were no associations between the neurophysiological and apathy measures. CONCLUSIONS: We speculate that these changes in oscillatory power and connectivity reflect ongoing, frontally concentrated degenerative and compensatory processes associated with HD. SIGNIFICANCE: Our findings support the potential utility of quantitative EEG as a proximate marker of processing speed, but not apathy in HD.
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Doença de Huntington , Humanos , Doença de Huntington/diagnóstico , Estudos LongitudinaisRESUMO
Obsessive-Compulsive Disorder (OCD) is a mental health condition causing significant decline in the quality of life of sufferers and the limited knowledge on the pathophysiology hinders successful treatment. The aim of the current study was to examine electroencephalographic (EEG) findings of OCD to broaden our understanding of the disease. Resting-state eyes-closed EEG data was recorded from 25 individuals with OCD and 27 healthy controls (HC). The 1/f arrhythmic activity was removed prior to computing oscillatory powers of all frequency bands (delta, theta, alpha, beta, gamma). Cluster-based permutation was used for between-group statistical analyses, and comparisons were performed for the 1/f slope and intercept parameters. Functional connectivity (FC) was measured using coherence and debiased weighted phase lag index (d-wPLI), and statistically analyzed using the Network Based Statistic method. Compared to HC, the OCD group showed increased oscillatory power in the delta and theta bands in the fronto-temporal and parietal brain regions. However, there were no significant between-group findings in other bands or 1/f parameters. The coherence measure showed significantly reduced FC in the delta band in OCD compared to HC but the d-wPLI analysis showed no significant differences. OCD is associated with raised oscillatory power in slow frequency bands in the fronto-temporal brain regions, which agrees with the previous literature and therefore is a potential biomarker. Although delta coherence was found to be lower in OCD, due to inconsistencies found between measures and the previous literature, further research is required to ascertain definitive conclusions.
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Transtorno Obsessivo-Compulsivo , Qualidade de Vida , Humanos , Eletroencefalografia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Imageamento por Ressonância MagnéticaRESUMO
The mechanisms that underpin recovery following mild traumatic brain injury (mTBI) remain poorly understood. Identifying neurophysiological markers and their functional significance is necessary to develop diagnostic and prognostic indicators of recovery. The current study assessed 30 participants in the subacute phase of mTBI (10-31 days post-injury) and 28 demographically matched controls. Participants also completed 3 month (mTBI: N = 21, control: N = 25) and 6 month (mTBI: N = 15, control: N = 25) follow up sessions to track recovery. At each time point, a battery of clinical, cognitive, and neurophysiological assessments was completed. Neurophysiological measures included resting-state electroencephalography (EEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG). Outcome measures were analysed using mixed linear models (MLM). Group differences in mood, post-concussion symptoms and resting-state EEG resolved by 3 months, and recovery was maintained at 6 months. On TMS-EEG derived neurophysiological measures of cortical reactivity, group differences ameliorated at 3 months but re-emerged at 6 months, while on measures of fatigue, group differences persisted across all time points. Persistent neurophysiological changes and greater fatigue in the absence of measurable cognitive impairment may suggest the impact of mTBI on neuronal communication may leads to increased neural effort to maintain efficient function. Neurophysiological measures to track recovery may help identify both temporally optimal windows and therapeutic targets for the development of new treatments in mTBI.
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Concussão Encefálica , Humanos , Concussão Encefálica/psicologia , Eletroencefalografia , Estimulação Magnética Transcraniana , Neurônios , CogniçãoRESUMO
BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric condition leading to significant distress and poor quality of life. Successful treatment of OCD is restricted by the limited knowledge about its pathophysiology. This study aimed to investigate the pathophysiology of OCD using electroencephalographic (EEG) event-related potentials (ERPs), elicited from multiple tasks to characterise disorder-related differences in underlying brain activity across multiple neural processes. METHODS: ERP data were obtained from 25 OCD patients and 27 age- and sex-matched healthy controls (HCs) by recording EEG during flanker and go/nogo tasks. Error-related negativity (ERN) was elicited by the flanker task, while N200 and P300 were generated using the go/nogo task. Primary comparisons of the neural response amplitudes and the topographical distribution of neural activity were conducted using scalp field differences across all time points and electrodes. RESULTS: Compared to HCs, the OCD group showed altered ERP distributions. Contrasting with the previous literature on ERN and N200 topographies in OCD where fronto-central negative voltages were reported, we detected positive voltages. Additionally, the P300 was found to be less negative in the frontal regions. None of these ERP findings were associated with OCD symptom severity. CONCLUSIONS: These results indicate that individuals with OCD show altered frontal neural activity across multiple executive function-related processes, supporting the frontal dysfunction theory of OCD. Furthermore, due to the lack of association between altered ERPs and OCD symptom severity, they may be considered potential candidate endophenotypes for OCD.
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Transtorno Obsessivo-Compulsivo , Qualidade de Vida , Humanos , Potenciais Evocados/fisiologia , Encéfalo , Eletroencefalografia/métodosRESUMO
We investigated the effects of transcranial alternating current stimulation (tACS) targeted to the medial prefrontal cortex (mPFC) on resting electroencephalographic (EEG) indices of oscillatory power, aperiodic exponent and offset, and functional connectivity in 22 late premanifest and early manifest stage individuals with HD and 20 neurotypical controls. Participants underwent three 20-minute sessions of tACS at least 72 hours apart; one session at alpha frequency (either each participant's Individualised Alpha Frequency (IAF), or 10 Hz when an IAF was not detected); one session at delta frequency (2 Hz); and a session of sham tACS. Session order was randomised and counterbalanced across participants. EEG recordings revealed a reduction of the spectral exponent ('flattening' of the 1/f slope) of the eyes-open aperiodic signal in participants with HD following alpha-tACS, suggestive of an enhancement in excitatory tone. Contrary to expectation, there were no changes in oscillatory power or functional connectivity in response to any of the tACS conditions in the participants with HD. By contrast, alpha-tACS increased delta power in neurotypical controls, who further demonstrated significant increases in theta power and theta functional connectivity in response to delta-tACS. This study contributes to the rapidly growing literature on the potential experimental and therapeutic applications of tACS by examining neurophysiological outcome measures in people with HD as well as neurotypical controls.
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Doença de Huntington , Estimulação Transcraniana por Corrente Contínua , Humanos , Eletroencefalografia , Olho , DescansoRESUMO
We investigated the effects of transcranial alternating current stimulation (tACS) targeted to the bilateral medial prefrontal cortex (mPFC) and administered at either delta or alpha frequencies, on brain activity and apathy in people with Huntington's disease (HD) (n = 17). Given the novelty of the protocol, neurotypical controls (n = 20) were also recruited. All participants underwent three 20-min sessions of tACS; one session at alpha frequency (Individualised Alpha Frequency (IAF), or 10 Hz when an IAF was not detected); one session at delta frequency (2 Hz); and a session of sham tACS. Participants completed the Monetary Incentive Delay (MID) task with simultaneous recording of EEG immediately before and after each tACS condition. The MID task presents participants with cues signalling potential monetary gains or losses that increase activity in key regions of the cortico-basal ganglia-thalamocortical networks, with dysfunction of the latter network being implicated in the pathophysiology of apathy. We used the P300 and Contingent Negative Variation (CNV) event-related potentials elicited during the MID task as markers of mPFC engagement. HD participants' CNV amplitude significantly increased in response to alpha-tACS, but not delta-tACS or sham. Neurotypical controls' P300 and CNV were not modulated by any of the tACS conditions, but they did demonstrate a significant decrease in post-target response times following alpha-tACS. We present this as preliminary evidence of the ability of alpha-tACS to modulate brain activity associated with apathy in HD.
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Apatia , Doença de Huntington , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Eletroencefalografia , Doença de Huntington/terapia , Potenciais Evocados/fisiologiaRESUMO
BACKGROUND: Despite efforts to improve targeting accuracy of the dorsolateral prefrontal cortex (DLPFC) as a repetitive transcranial magnetic stimulation (rTMS) target for Major Depressive Disorder (MDD), the heterogeneity in clinical response remains unexplained. OBJECTIVE: We sought to compare the patterns of functional connectivity from the DLPFC treatment site in patients with MDD who were TMS responders to those who were TMS non-responders. METHODS: Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI, and diffusion weighted imaging scans were obtained from 37 participants before they underwent a course of rTMS to left Brodmann area 46. A novel machine learning method was utilized to identify brain regions associated with each item of the Beck's Depression Inventory II (BDI-II), and for 26 participants who underwent rTMS treatment over the left Brodmann area 46, identify regions differentiating rTMS responders and non-responders. RESULTS: Nine parcels of the Human Connectome Project Multimodal Parcellation Atlas matched to at least three items of the Beck's Depression Inventory II (BDI-II) as predictors of response to rTMS, with many in the temporal, parietal and cingulate cortices. Additionally, pre-treatment mapping for 17 items of the BDI-II demonstrated significant variability in symptom to parcel mapping. When parcels associated with symptom presence and symptom resolution were compared, 15 parcels were uniquely associated with resolution (potential targets), and 12 parcels were associated with both symptom presence and resolution (blockers or biomarkers). CONCLUSIONS: Machine learning approaches show promise for the development of pathoanatomical diagnosis and treatment algorithms for MDD. Prospective studies are required to facilitate clinical translation.
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Conectoma , Transtorno Depressivo Maior , Humanos , Estimulação Magnética Transcraniana/métodos , Conectoma/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Depressão , Córtex Pré-Frontal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Resultado do TratamentoRESUMO
The brain works as an organised, network-like structure of functionally interconnected regions. Disruptions to interconnectivity in certain networks have been linked to symptoms of depression and impairments in cognition. Electroencephalography (EEG) is a low-burden tool by which differences in functional connectivity (FC) can be assessed. This systematic review aims to provide a synthesis of evidence relating to EEG FC in depression. A comprehensive electronic literature search for terms relating to depression, EEG, and FC was conducted on studies published before the end of November 2021, according to PRISMA guidelines. Studies comparing EEG measures of FC of individuals with depression to that of healthy control groups were included. Data was extracted by two independent reviewers, and the quality of EEG FC methods was assessed. Fifty-two studies assessing EEG FC in depression were identified: 36 assessed resting-state FC, and 16 assessed task-related or other (i.e., sleep) FC. Somewhat consistent findings in resting-state studies suggest for no differences between depression and control groups in EEG FC in the delta and gamma frequencies. However, while most resting-state studies noted a difference in alpha, theta, and beta, no clear conclusions could be drawn about the direction of the difference, due to considerable inconsistencies between study design and methodology. This was also true for task-related and other EEG FC. More robust research is needed to understand the true differences in EEG FC in depression. Given that the FC between brain regions drives behaviour, cognition, and emotion, characterising how FC differs in depression is essential for understanding the aetiology of depression.
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Encéfalo , Depressão , Humanos , Encéfalo/fisiologia , Depressão/fisiopatologia , Eletroencefalografia , Estudos de Casos e ControlesRESUMO
Chimeric antigen receptor T-cell therapy (CART) has extended survival of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). However, limited durability of response and prevalent toxicities remain problematic. Identifying patients who are at high risk of disease progression, toxicity, and death would inform treatment decisions. Although the cumulative illness rating scale (CIRS) has been shown to correlate with survival in B-cell malignancies, no prognostic score has been independently validated in CART recipients. We retrospectively identified 577 patients with relapsed/refractory DLBCL indicated for CART at 9 academic centers to form a learning cohort (LC). Random survival forest modeling of overall survival (OS) and progression-free survival (PFS) was performed to determine the most influential CIRS organ systems and severity grades. The presence of a severe comorbidity (CIRS score ≥ 3) in the respiratory, upper gastrointestinal, hepatic, or renal system, herein termed "Severe4," had the greatest impact on post-CART survival. Controlling for other prognostic factors (number of prior therapies, Eastern Cooperative Oncology Group performance status, BCL6 translocation, and molecular subtype), Severe4 was strongly associated with shorter PFS and OS in the LC and in an independent single-center validation cohort (VC). Severe4 was also a significant predictor of grade ≥3 cytokine release syndrome in the LC, while maintaining this trend in the VC. Thus, our results indicate that adverse outcomes for patients with DLBCL meant to receive CART can be predicted using a simplified CIRS-derived comorbidity index.
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Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , ComorbidadeRESUMO
OBJECTIVE: The ability of the brain to recover following neurological insult is of interest for mild traumatic brain injury (mTBI) populations. Investigating whether non-invasive brain stimulation (NIBS) can modulate neurophysiology and cognition may lead to the development of therapeutic interventions post injury. The purpose of this study was to investigate neurobiological effects of one session of intermittent theta burst stimulation (iTBS) to the dorsolateral prefrontal cortex (DLPFC) in participants recovering from mTBI. METHOD: Changes to neurophysiology were assessed with electroencephalography (EEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG). Digit span working memory accuracy assessed cognitive performance. 30 patients were assessed within one-month of sustaining a mTBI and 26 demographically matched controls were assessed. Participants were also assessed at 3-months (mTBI: N = 21, control: N = 26) and 6-months (mTBI: N = 15, control: N = 24). RESULTS: Analyses demonstrated iTBS did not reliably modulate neurophysiological activity, and no differences in cognitive performance were produced by iTBS at any assessment time-point. CONCLUSIONS: Factors responsible for our null results are unclear. Possible limitations to our experimental design are discussed. SIGNIFICANCE: Our findings suggest additional research is required to establish the effects of iTBS on plasticity following mTBI, prior to therapeutic application. DATA AND CODE AVAILABILITY STATEMENT: We do not have ethical approval to make this data publicly available, as our approval predated our inclusion of such approvals (which we now do routinely).
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Concussão Encefálica , Humanos , Concussão Encefálica/terapia , Estimulação Magnética Transcraniana/métodos , Córtex Pré-Frontal/fisiologia , Eletroencefalografia/métodos , EncéfaloRESUMO
Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone. We conducted a three-institution retrospective study, aiming to evaluate the role of short-term adjuvant chemotherapy in managing moderate DS for patients with low- or intermediate-risk APL initially treated with ATRA/ATO only protocols. We evaluated the difference in incidence and duration of moderate DS in APL patients who were treated with ATRA/ATO with or without adjuvant chemotherapy. 57 low- or intermediate-risk APL patients were retrospectively identified and included for this study; 36 patients received ATRA/ATO only induction treatment, and 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy. Similar proportions of patients experienced DS in both groups (66.7% vs. 81.0%, P = 0.246). The median duration of DS resolution in patients receiving ATRA/ATO only was 17 days (n = 23), and in patients receiving combination therapy was 8 days (n = 16) (P = 0.0001). The lengths of hospital stay in patients receiving ATRO/ATO only was 38 days (n = 7), and in patients receiving combination therapy was 14 days (n = 17) (P = 0.0007). In conclusion, adding adjuvant chemotherapy to ATRA/ATO only protocol may reduce the duration of DS and the length of hospital stay during APL induction treatment.
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We present two cases of nephrotic syndrome with minimal change disease after the Pfizer-BioNTech COVID-19 vaccine. We discuss the initial presentation, investigation and management of these patients along with a discussion around the current evidence base for vaccine-induced nephrotic syndrome.
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COVID-19 , Nefrose Lipoide , Síndrome Nefrótica , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Nefrose Lipoide/induzido quimicamente , Síndrome Nefrótica/etiologia , SARS-CoV-2RESUMO
INTRODUCTION: The utility of dose escalation after positive positron emission tomography following 2 cycles of ABVD (PET2) for Hodgkin Lymphoma (HL) remains controversial. We describe the United States real-world practice patterns for PET2 positive patients. PATIENTS AND METHODS: Data was collected from 15 sites on PET2 positive HL patients after receiving frontline treatment between January, 2015 and June, 2019. Descriptive analyses between those with therapy change and those continuing initial therapy were assessed. RESULTS: A total of 129 patients were identified; 111 (86%) were treated with ABVD therapy and 18 (14%) with an alternate regimen. At PET2 assessment, 74.4% (96/129) had Deauville score (DS) 4 and 25.6% (33/129) had DS 5. Of the 66 limited stage (LS) patients with PET2 DS score of 4/5, 77.3% (51/66) continued initial therapy and 22.7% (15/66) changed to escalated therapy. The 12-month progression-free survival (PFS) for DS 4/5 LS patients was 67.0% (95% CI; 54.9-81.7) for patients without escalation compared with 51.4% (95% CI; 30.8-85.8) for those who escalated. Of the 63 DS 4/5 patients with advanced stage (AS) disease, 76.2% (48/63) continued initial therapy and 23.8% (15/63) changed to escalated therapy. The 12-month PFS for DS 4/5 AS patients was 38.3% (95% CI: 26.3%-55.7%) for patients without escalation compared with 57.1% (95% CI: 36.3-89.9) for those with escalation. CONCLUSION: A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients.
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Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Tomografia por Emissão de Pósitrons/métodos , Vimblastina/uso terapêuticoRESUMO
BACKGROUND: Alzheimer's disease (AD) is characterized by a progressive decline in cognitive functioning for which there is a stark lack of effective treatments. Investigating the neurophysiological markers of symptom severity in AD may aid in the identification of alternative treatment targets. OBJECTIVE: In the current study we used a multimodal approach to investigate the association between functional connectivity (specifically between scalp electrodes placed over frontal and parietal regions) and symptom severity in AD, and to explore the relationship between connectivity and cortical excitability. METHODS: 40 people with AD (25 mild severity, 15 moderate severity) underwent neurobiological assessment (resting state electroencephalography (EEG) and prefrontal transcranial magnetic stimulation (TMS) with EEG) and cognitive assessment. Neurobiological outcomes were resting state functional connectivity and TMS-evoked potentials. Cognitive outcomes were scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, and a measure of episodic verbal learning. RESULTS: Greater contralateral functional theta connectivity between frontal scalp electrodes and parietal scalp electrodes was associated with poorer cognitive performance. In addition, significant correlations were seen between the contralateral theta connectivity and the N100 and P60 TMS-evoked potentials measured from electrodes over the left dorsolateral prefrontal cortex. CONCLUSION: Together these findings provide initial support for the use of multimodal neurophysiological approaches to investigate potential therapeutic targets in AD. Suggestions for future research are discussed.
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Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Eletroencefalografia/métodos , Córtex Pré-Frontal/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Potenciais Evocados , Feminino , Humanos , Masculino , Análise de Regressão , Estimulação Magnética TranscranianaRESUMO
Brain connectivity can be estimated through many analyses applied to electroencephalography (EEG) data. However, substantial heterogeneity in the implementation of connectivity methods exists. Heterogeneity in conceptualization of connectivity measures, data collection, or data preprocessing may be associated with variability in robustness of measurement. While it is difficult to compare the results of studies using different EEG connectivity measures, standardization of processing and reporting may facilitate the task. We discuss how factors such as referencing, epoch length and number, controls for volume conduction, artifact removal, and statistical control of multiple comparisons influence the EEG connectivity estimate for connectivity measures, and what can be done to control for potential confounds associated with these factors. Based on the results reported in previous literature, this article presents recommendations and a novel checklist developed for quality assessment of EEG connectivity studies. This checklist and its recommendations are made in an effort to draw attention to factors that may influence connectivity estimates and factors that need to be improved in future research. Standardization of procedures and reporting in EEG connectivity may lead to EEG connectivity studies being made more synthesizable and comparable despite variations in the methodology underlying connectivity estimates.
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Lista de Checagem , Eletroencefalografia , Encéfalo , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , HumanosRESUMO
Cognitive impairment is highly prevalent in schizophrenia and treatment options are severely limited. A greater understanding of the pathophysiology of impaired cognition would have broad implications, including for the development of effective treatments. In the current study we used a multimodal approach to identify neurophysiological markers of cognitive impairment in schizophrenia. Fifty-seven participants (30 schizophrenia, 27 controls) underwent neurobiological assessment (electroencephalography [EEG] and Transcranial Magnetic Stimulation combined with EEG [TMS-EEG]) and assessment of cognitive functioning using an n-back task and the MATRICS Consensus Cognitive Battery. Neurobiological outcome measures included oscillatory power during a 2-back task, TMS-related oscillations and TMS-evoked potentials (TEPs). Cognitive outcome measures were d prime and accurate reaction time on the 2-back and MATRICS domain scores. Compared to healthy controls, participants with schizophrenia showed significantly reduced theta oscillations in response to TMS, and trend level decreases in task-related theta and cortical reactivity (i.e. reduced N100 and N40 TEPs). Participants with schizophrenia also showed significantly impaired cognitive performance across all measures. Correlational analysis identified significant associations between cortical reactivity and TMS-related oscillations in both groups; and trend level associations between task-related oscillations and impaired cognition in schizophrenia. The current study provides experimental support for possible neurophysiological markers of cognitive impairment in schizophrenia. The potential implications of these findings, including for treatment development, are discussed.