RESUMO
Recent electroencephalography (EEG) studies have shown that patterns of brain activity can be used to differentiate amyotrophic lateral sclerosis (ALS) and control groups. These differences can be interrogated by examining EEG microstates, which are distinct, reoccurring topographies of the scalp's electrical potentials. Quantifying the temporal properties of the four canonical microstates can elucidate how the dynamics of functional brain networks are altered in neurological conditions. Here we have analysed the properties of microstates to detect and quantify signal-based abnormality in ALS. High-density resting-state EEG data from 129 people with ALS and 78 HC were recorded longitudinally over a 24-month period. EEG topographies were extracted at instances of peak global field power to identify four microstate classes (labelled A-D) using K-means clustering. Each EEG topography was retrospectively associated with a microstate class based on global map dissimilarity. Changes in microstate properties over the course of the disease were assessed in people with ALS and compared with changes in clinical scores. The topographies of microstate classes remained consistent across participants and conditions. Differences were observed in coverage, occurrence, duration, and transition probabilities between ALS and control groups. The duration of microstate class B and coverage of microstate class C correlated with lower limb functional decline. The transition probabilities A to D, C to B and C to B also correlated with cognitive decline (total ECAS) in those with cognitive and behavioural impairments. Microstate characteristics also significantly changed over the course of the disease. Examining the temporal dependencies in the sequences of microstates revealed that the symmetry and stationarity of transition matrices were increased in people with late-stage ALS. These alterations in the properties of EEG microstates in ALS may reflect abnormalities within the sensory network and higher-order networks. Microstate properties could also prospectively predict symptom progression in those with cognitive impairments.
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Esclerose Lateral Amiotrófica , Disfunção Cognitiva , Humanos , Eletroencefalografia , Estudos Retrospectivos , Encéfalo , Mapeamento Encefálico , Disfunção Cognitiva/etiologiaRESUMO
BACKGROUND: Re-emergent tremor is characterized as a continuation of resting tremor and is often highly therapy refractory. This study examines variations in brain activity and oscillatory responses between resting and re-emergent tremors in Parkinson's disease. METHODS: Forty patients with Parkinson's disease (25 males, mean age, 66.78 ± 5.03 years) and 40 age- and sex-matched healthy controls were included in the study. Electroencephalogram and electromyography signals were simultaneously recorded during resting and re-emergent tremors in levodopa on and off states for patients and mimicked by healthy controls. Brain activity was localized using the beamforming technique, and information flow between sources was estimated using effective connectivity. Cross-frequency coupling was used to assess neuronal oscillations between tremor frequency and canonical frequency oscillations. RESULTS: During levodopa on, differences in brain activity were observed in the premotor cortex and cerebellum in both the patient and control groups. However, Parkinson's disease patients also exhibited additional activity in the primary sensorimotor cortex. On withdrawal of levodopa, different source patterns were observed in the supplementary motor area and basal ganglia area. Additionally, levodopa was found to suppress the strength of connectivity (P < 0.001) between the identified sources and influence the tremor frequency-related coupling, leading to a decrease in ß (P < 0.001) and an increase in γ frequency coupling (P < 0.001). CONCLUSIONS: Distinct variations in cortical-subcortical brain activity are evident in tremor phenotypes. The primary sensorimotor cortex plays a crucial role in the generation of re-emergent tremor. Moreover, oscillatory neuronal responses in pathological ß and prokinetic γ activity are specific to tremor phenotypes. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Eletromiografia , Levodopa , Doença de Parkinson , Tremor , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Masculino , Feminino , Tremor/fisiopatologia , Tremor/etiologia , Pessoa de Meia-Idade , Idoso , Levodopa/uso terapêutico , Levodopa/farmacologia , Ritmo Gama/fisiologia , Ritmo Gama/efeitos dos fármacos , Ritmo beta/fisiologia , Ritmo beta/efeitos dos fármacos , Eletroencefalografia/métodos , Antiparkinsonianos/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: Resting-state electroencephalography (EEG) holds promise for assessing brain networks in amyotrophic lateral sclerosis (ALS). We investigated whether neural ß-band oscillations in the sensorimotor network could serve as an objective quantitative measure of progressive motor impairment and functional disability in ALS patients. METHODS: Resting-state EEG was recorded in 18 people with ALS and 38 age- and gender-matched healthy controls. We estimated source-localized ß-band spectral power in the sensorimotor cortex. Clinical evaluation included lower (LMN) and upper motor neuron scores, Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, fine motor function (FMF) subscore, and progression rate. Correlations between clinical scores and ß-band power were analysed and corrected using a false discovery rate of q = 0.05. RESULTS: ß-Band power was significantly lower in people with ALS than controls (p = 0.004), and correlated with LMN score (R = -0.65, p = 0.013), FMF subscore (R = -0.53, p = 0.036), and FMF progression rate (R = 0.52, p = 0.036). CONCLUSIONS: ß-Band spectral power in the sensorimotor cortex reflects clinically evaluated motor impairment in ALS. This technology merits further investigation as a biomarker of progressive functional disability.
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Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Eletroencefalografia , Neurônios Motores , Encéfalo , Mapeamento EncefálicoRESUMO
Primary lateral sclerosis (PLS) is a slowly progressing disorder, which is characterized primarily by the degeneration of upper motor neurons (UMNs) in the primary motor area (M1). It is not yet clear how the function of sensorimotor networks beyond M1 are affected by PLS. The aim of this study was to use cortico-muscular coherence (CMC) to characterize the oscillatory drives between cortical regions and muscles during a motor task in PLS and to examine the relationship between CMC and the level of clinical impairment. We recorded EEG and EMG from hand muscles in 16 participants with PLS and 18 controls during a pincer-grip task. In PLS, higher CMC was observed over contralateral-M1 (α- and γ-band) and ipsilateral-M1 (ß-band) compared with controls. Significant correlations between clinically assessed UMN scores and CMC measures showed that higher clinical impairment was associated with lower CMC over contralateral-M1/frontal areas, higher CMC over parietal area, and both higher and lower CMC (in different bands) over ipsilateral-M1. The results suggest an atypical engagement of both contralateral and ipsilateral M1 during motor activity in PLS, indicating the presence of pathogenic and/or adaptive/compensatory alterations in neural activity. The findings demonstrate the potential of CMC for identifying dysfunction within the sensorimotor networks in PLS.
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Córtex Motor , Doença dos Neurônios Motores , Humanos , Eletromiografia/métodos , Córtex Motor/fisiologia , Músculo Esquelético/fisiologia , MãosRESUMO
Amyotrophic lateral sclerosis is a devastating disease characterized primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. Amyotrophic lateral sclerosis is both clinically and biologically heterogeneous. Subgrouping is currently undertaken using clinical parameters, such as site of symptom onset (bulbar or spinal), burden of disease (based on the modified El Escorial Research Criteria) and genomics in those with familial disease. However, with the exception of genomics, these subcategories do not take into account underlying disease pathobiology, and are not fully predictive of disease course or prognosis. Recently, we have shown that resting-state EEG can reliably and quantitatively capture abnormal patterns of motor and cognitive network disruption in amyotrophic lateral sclerosis. These network disruptions have been identified across multiple frequency bands, and using measures of neural activity (spectral power) and connectivity (comodulation of activity by amplitude envelope correlation and synchrony by imaginary coherence) on source-localized brain oscillations from high-density EEG. Using data-driven methods (similarity network fusion and spectral clustering), we have now undertaken a clustering analysis to identify disease subphenotypes and to determine whether different patterns of disruption are predictive of disease outcome. We show that amyotrophic lateral sclerosis patients (n = 95) can be subgrouped into four phenotypes with distinct neurophysiological profiles. These clusters are characterized by varying degrees of disruption in the somatomotor (α-band synchrony), frontotemporal (ß-band neural activity and γl-band synchrony) and frontoparietal (γl-band comodulation) networks, which reliably correlate with distinct clinical profiles and different disease trajectories. Using an in-depth stability analysis, we show that these clusters are statistically reproducible and robust, remain stable after reassessment using a follow-up EEG session, and continue to predict the clinical trajectory and disease outcome. Our data demonstrate that novel phenotyping using neuroelectric signal analysis can distinguish disease subtypes based exclusively on different patterns of network disturbances. These patterns may reflect underlying disease neurobiology. The identification of amyotrophic lateral sclerosis subtypes based on profiles of differential impairment in neuronal networks has clear potential in future stratification for clinical trials. Advanced network profiling in amyotrophic lateral sclerosis can also underpin new therapeutic strategies that are based on principles of neurobiology and designed to modulate network disruption.
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Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/genética , Encéfalo , Eletroencefalografia , Humanos , NeurôniosRESUMO
OBJECTIVE: To identify cortical regions engaged during the sustained attention to response task (SART) and characterize changes in their activity associated with the neurodegenerative condition amyotrophic lateral sclerosis (ALS). METHODS: High-density electroencephalography (EEG) was recorded from 33 controls and 23 ALS patients during a SART paradigm. Differences in associated event-related potential peaks were measured for Go and NoGo trials. Sources active during these peaks were localized, and ALS-associated differences were quantified. RESULTS: Go and NoGo N2 and P3 peak sources were localized to the left primary motor cortex, bilateral dorsolateral prefrontal cortex (DLPFC), and lateral posterior parietal cortex (PPC). NoGo trials evoked greater bilateral medial PPC activity during N2 and lesser left insular, PPC and DLPFC activity during P3. Widespread cortical hyperactivity was identified in ALS during P3. Changes in the inferior parietal lobule and insular activity provided very good discrimination (AUROC > 0.75) between patients and controls. Activation of the right precuneus during P3 related to greater executive function in ALS, indicative of a compensatory role. INTERPRETATION: The SART engages numerous frontal and parietal cortical structures. SART-EEG measures correlate with specific cognitive impairments that can be localized to specific structures, aiding in differential diagnosis.
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Esclerose Lateral Amiotrófica/fisiopatologia , Atenção/fisiologia , Encéfalo/fisiopatologia , Função Executiva/fisiologia , Rede Nervosa/fisiopatologia , Adulto , Idoso , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Amyotrophic lateral sclerosis (ALS) is a terminal progressive adult-onset neurodegeneration of the motor system. Although originally considered a pure motor degeneration, there is increasing evidence of disease heterogeneity with varying degrees of extra-motor involvement. How the combined motor and nonmotor degeneration occurs in the context of broader disruption in neural communication across brain networks has not been well characterized. Here, we have performed high-density crossectional and longitudinal resting-state electroencephalography (EEG) recordings on 100 ALS patients and 34 matched controls, and have identified characteristic patterns of altered EEG connectivity that have persisted in longitudinal analyses. These include strongly increased EEG coherence between parietal-frontal scalp regions (in γ-band) and between bilateral regions over motor areas (in θ-band). Correlation with structural MRI from the same patients shows that disease-specific structural degeneration in motor areas and corticospinal tracts parallels a decrease in neural activity over scalp motor areas, while the EEG over the scalp regions associated with less extensively involved extra-motor regions on MRI exhibit significantly increased neural communication. Our findings demonstrate that EEG-based connectivity mapping can provide novel insights into progressive network decline in ALS. These data pave the way for development of validated cost-effective spectral EEG-based biomarkers that parallel changes in structural imaging.
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Esclerose Lateral Amiotrófica/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Eletroencefalografia/tendências , Imageamento por Ressonância Magnética/tendências , Rede Nervosa/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/fisiopatologia , Córtex Cerebral/fisiopatologia , Estudos de Coortes , Eletroencefalografia/métodos , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Tratos Piramidais/fisiopatologiaRESUMO
Ankle joint plays a critical role in daily activities involving interactions with environment using force and position control. Neuromechanical dysfunctions (e.g., due to stroke or brain injury), therefore, have a major impact on individuals' quality of life. The effective design of neuro-rehabilitation protocols for robotic rehabilitation platforms relies on understanding the control characteristics of the ankle joint in interaction with external environment using force and position, as the findings in upper limb may not be generalizable to the lower limb. This study aimed to characterize the skilled performance of ankle joint in visuomotor position and force control. A two-degree-of-freedom (DOF) robotic footplate was used to measure individuals' force and position. Healthy individuals (n = 27) used ankle force or position for point-to-point and tracking control tasks in 1-DOF and 2-DOF virtual game environments. Subjects' performance was quantified as a function of accuracy and completion time. In contrast to comparable performance in 1-DOF control tasks, the performance in 2-DOF tasks was different and had characteristic patterns in the position and force conditions, with a significantly better performance for position. Subjective questionnaires on the perceived difficulty matched the objective experimental results, suggesting that the poor performance in force control was not due to experimental set-up or fatigue but can be attributed to the different levels of challenge needed in neural control. It is inferred that in visuomotor coordination, the neuromuscular specialization of ankle provides better control over position rather than force. These findings can inform the design of neuro-rehabilitation platforms, selection of effective tasks and therapeutic protocols.
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Articulação do Tornozelo , Destreza Motora , Percepção Visual , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Contração Isométrica , Masculino , Atividade Motora , Reabilitação Neurológica , Amplitude de Movimento Articular , Robótica , Inquéritos e Questionários , Terapia Assistida por Computador , Jogos de Vídeo , Adulto JovemRESUMO
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor function, with additional evidence of extensive nonmotor involvement. Despite increasing recognition of the disease as a multisystem network disorder characterised by impaired connectivity, the precise neuroelectric characteristics of impaired cortical communication remain to be fully elucidated. Here, we characterise changes in functional connectivity using beamformer source analysis on resting-state electroencephalography recordings from 74 ALS patients and 47 age-matched healthy controls. Spatiospectral characteristics of network changes in the ALS patient group were quantified by spectral power, amplitude envelope correlation (co-modulation) and imaginary coherence (synchrony). We show patterns of decreased spectral power in the occipital and temporal (δ- to ß-band), lateral/orbitofrontal (δ- to θ-band) and sensorimotor (ß-band) regions of the brain in patients with ALS. Furthermore, we show increased co-modulation of neural oscillations in the central and posterior (δ-, θ- and γl -band) and frontal (δ- and γl -band) regions, as well as decreased synchrony in the temporal and frontal (δ- to ß-band) and sensorimotor (ß-band) regions. Factorisation of these complex connectivity patterns reveals a distinct disruption of both motor and nonmotor networks. The observed changes in connectivity correlated with structural MRI changes, functional motor scores and cognitive scores. Characteristic patterned changes of cortical function in ALS signify widespread disease-associated network disruption, pointing to extensive dysfunction of both motor and cognitive networks. These statistically robust findings, that correlate with clinical scores, provide a strong rationale for further development as biomarkers of network disruption for future clinical trials.
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Esclerose Lateral Amiotrófica/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto , Idoso , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/psicologia , Ritmo beta , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Cognição , Ritmo Delta , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Testes Neuropsicológicos , Desempenho Psicomotor , Ritmo TetaRESUMO
Advanced neuroimaging has increased understanding of the pathogenesis and spread of disease, and offered new therapeutic targets. MRI and positron emission tomography have shown that neurodegenerative diseases including Alzheimer's disease (AD), Lewy body dementia (LBD), Parkinson's disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are associated with changes in brain networks. However, the underlying neurophysiological pathways driving pathological processes are poorly defined. The gap between what imaging can discern and underlying pathophysiology can now be addressed by advanced techniques that explore the cortical neural synchronisation, excitability and functional connectivity that underpin cognitive, motor, sensory and other functions. Transcranial magnetic stimulation can show changes in focal excitability in cortical and transcortical motor circuits, while electroencephalography and magnetoencephalography can now record cortical neural synchronisation and connectivity with good temporal and spatial resolution.Here we reflect on the most promising new approaches to measuring network disruption in AD, LBD, PD, FTD, MS, and ALS. We consider the most groundbreaking and clinically promising studies in this field. We outline the limitations of these techniques and how they can be tackled and discuss how these novel approaches can assist in clinical trials by predicting and monitoring progression of neurophysiological changes underpinning clinical symptomatology.
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Rede Nervosa/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Doença de Alzheimer/fisiopatologia , Esclerose Lateral Amiotrófica/fisiopatologia , Eletroencefalografia , Demência Frontotemporal/fisiopatologia , Humanos , Doença por Corpos de Lewy/fisiopatologia , Magnetoencefalografia , Doença de Parkinson/fisiopatologia , Estimulação Magnética TranscranianaRESUMO
The study of object manipulation has been largely confined to discrete tasks, where accuracy, mechanical effort, or smoothness were examined to explain subjects' preferred movements. This study investigated a rhythmic manipulation task, which involved continuous interaction with a nonlinear object that led to unpredictable object behavior. Using a simplified virtual version of the task of carrying a cup of coffee, we studied how this unpredictable object behavior affected the selected strategies. The experiment was conducted in a virtual set-up, where subjects moved a cup with a ball inside, modeled by cart-and-pendulum dynamics. Inverse dynamics calculations of the system showed that performing the task with different amplitudes and relative phases required different force profiles and rendered the object's dynamics with different degrees of predictability (quantified by Mutual Information between the applied force and the cup kinematics and its sensitivity). Subjects (nâ=â8) oscillated the virtual cup between two targets via a robotic manipulandum, paced by a metronome at 1 Hz for 50 trials, each lasting 45 s. They were free to choose their movement amplitude and relative phase between the ball and cup. Experimental results showed that subjects increased their movement amplitudes, which rendered the interactions with the object more predictable and with lower sensitivity to the execution variables. These solutions were associated with higher average exerted force and lower object smoothness, contradicting common expectations from studies on discrete object manipulation and unrestrained movements. Instead, the findings showed that humans selected strategies with higher predictability of interaction dynamics. This finding expressed that humans seek movement strategies where force and kinematics synchronize to repeatable patterns that may require less sensorimotor information processing.
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Fenômenos Biomecânicos/fisiologia , Modelos Teóricos , Movimento/fisiologia , Adulto , Feminino , Mãos/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Robótica , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
The electroencephalographic (EEG) activity patterns in humans during motor behaviour provide insight into normal motor control processes and for diagnostic and rehabilitation applications. While the patterns preceding brisk voluntary movements, and especially movement execution, are well described, there are few EEG studies that address the cortical activation patterns seen in isometric exertions and their planning. In this paper, we report on time and time-frequency EEG signatures in experiments in normal subjects (n=8), using multichannel EEG during motor preparation, planning and execution of directional centre-out arm isometric exertions performed at the wrist in the horizontal plane, in response to instruction-delay visual cues. Our observations suggest that isometric force exertions are accompanied by transient and sustained event-related potentials (ERP) and event-related (de-)synchronisations (ERD/ERS), comparable to those of a movement task. Furthermore, the ERPs and ERD/ERS are also observed during preparation and planning of the isometric task. Comparison of ear-lobe-referenced and surface Laplacian ERPs indicates the contribution of superficial sources in supplementary and pre-motor (FC(z)), parietal (CP(z)) and primary motor cortical areas (C1 and FC1) to ERPs (primarily negative peaks in frontal and positive peaks in parietal areas), but contribution of deep sources to sustained time-domain potentials (negativity in planning and positivity in execution). Transient and sustained ERD patterns in µ and ß frequency bands of ear-lobe-referenced and surface Laplacian EEG indicate the contribution of both superficial and deep sources to ERD/ERS. As no physical displacement happens during the task, we can infer that the underlying mechanisms of motor-related ERPs and ERD/ERS patterns do not only depend on change in limb coordinate or muscle-length-dependent ascending sensory information and are primary generated by motor preparation, direction-dependent planning and execution of isometric motor tasks. The results contribute to our understanding of the functions of different brain regions during voluntary motor tasks and their activity signatures in EEG can shed light on the relationships between large-scale recordings such as EEG and other recordings such as single unit activity and fMRI in this context.
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Sincronização Cortical/fisiologia , Potenciais Evocados/fisiologia , Processos Mentais/fisiologia , Atividade Motora/fisiologia , Córtex Motor/fisiologia , Adulto , Mapeamento Encefálico/métodos , Sinais (Psicologia) , Eletroencefalografia , Feminino , Humanos , Contração Isométrica/fisiologia , Masculino , Processamento de Sinais Assistido por ComputadorRESUMO
Despite development of accurate musculoskeletal models for human lumbar spine, the methods for prediction of muscle activity patterns in movements lack proper association with corresponding sensorimotor integrations. This paper uses the directional information of the Jacobian of the musculoskeletal system to orchestrate adaptive critic-based fuzzy neural controller modules for controlling a complex nonlinear redundant musculoskeletal system. The proposed controller is used to control a 3D 3-degree of freedom (DOF) musculoskeletal model of trunk, actuated by 18 muscles. The controller is capable of learning to control from sensory information, without relying on pre-assumed model parameters. Simulation results show satisfactory tracking of movements and the simulated muscle activation patterns conform to previous EMG experiments and optimization studies. The proposed controller can be used as a computationally inexpensive muscle activity generator to distinguish between neural and mechanical contributions to movement and for study of sensory versus motor origins of motor function and dysfunction in human spine.
Assuntos
Interfaces Cérebro-Computador , Vértebras Lombares/fisiologia , Modelos Biológicos , Movimento , Músculos/fisiologia , Inteligência Artificial , HumanosRESUMO
Objective: To establish if induced current direction across the motor cortex alters the sensitivity of transcranial magnetic stimulation (TMS)-evoked short-interval intracortical inhibition (SICI) as an ALS biomarker. Methods: Threshold tracking-TMS was undertaken in 35 people with ALS and 39 controls. Using a coil orientation which induces posterior-anterior (PA)-directed current across the motor cortex, SICI (1â¯ms and 3â¯ms interstimulus intervals) and intracortical facilitation (ICF, 10â¯ms interstimulus interval) were recorded. SICI3ms was also recorded using a coil orientation which induces anterior-posterior (AP)-directed current across the motor cortex. Results: At group level, SICI3ms-PA (AUROCâ¯=â¯0.7), SICI3ms-AP (AUROCâ¯=â¯0.8) and SICI1ms (AUROCâ¯=â¯0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICIPA sensitivity (AUROCâ¯=â¯0.76). Averaging SICI values across ISIs and orientations into a single SICI measure did not substantially improve sensitivity (AUROCâ¯=â¯0.81) compared to SICI3ms-AP alone. SICI3ms-AP and SICI3ms-PA did not significantly correlate (rhoâ¯=â¯0.19, pâ¯=â¯0.313), while SICI1ms-PA and SICI3ms-PA did (rhoâ¯=â¯0.37, pâ¯=â¯0.006). Further, those with ALS with the lowest SICI3ms-PA were not those with the lowest SICI3ms-AP. ICF was similar between groups (AUROCâ¯=â¯0.50). Conclusions: SICIPA and SICIAP are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS. Significance: Examining both SICIPA and SICIAP may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS.
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The execution of voluntary movements is primarily governed by the cerebral hemisphere contralateral to the moving limb. Previous research indicates that the ipsilateral motor network, comprising the primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM), plays a crucial role in the planning and execution of limb movements. However, the precise functions of this network and its interplay in different task contexts have yet to be fully understood. Twenty healthy right-handed participants (10 females, mean age 26.1 ± 4.6 years) underwent functional MRI scans while performing biceps brachii representations such as bilateral, unilateral flexion, and bilateral flexion-extension. Ipsilateral motor evoked potentials (iMEPs) were obtained from the identical set of participants in a prior study using transcranial magnetic stimulation (TMS) targeting M1 while employing the same motor tasks. The voxel time series was extracted based on the region of interest (M1, SMA, ventral PM and dorsal PM). Directed functinal connectivity was derived from the extracted time series using time-resolved partial directed coherence. We found increased connectivity from left-PMv to both sides M1, as well as right-PMv to both sides SMA, in unilateral flexion compared to bilateral flexion. Connectivity from left M1 to left-PMv, and left-SMA to right-PMd, also increased in both unilateral flexion and bilateral flexion-extension compared to bilateral flexion. However, connectivity between PMv and right-M1 to left-PMd decreased during bilateral flexion-extension compared to unilateral flexion. Additionally, during bilateral flexion-extension, the connectivity from right-M1 to right-SMA had a negative relationship with the area ratio of iMEP in the dominant side. Our results provide corroborating evidence for prior research suggesting that the ipsilateral motor network is implicated in the voluntary movements and underscores its involvement in cognitive processes such as movement planning and coordination. Moreover, ipsilateral connectivity from M1 to SMA on the dominant side can modulate the degree of ipsilateral M1 activation during bilateral antagonistic contraction.
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Treadmill training (TT) has been extensively used as an intervention to improve gait and mobility in patients with Parkinson's disease (PD). Regional and global effects on brain activity could be induced through TT. Training effects can lead to a beneficial shift of interregional connectivity towards a physiological range. The current work investigates the effects of TT on brain activity and connectivity during walking and at rest by using both functional near-infrared spectroscopy and functional magnetic resonance imaging. Nineteen PD patients (74.0 ± 6.59 years, 13 males, disease duration 10.45 ± 6.83 years) before and after 6 weeks of TT, along with 19 age-matched healthy controls were assessed. Interregional effective connectivity (EC) between cortical and subcortical regions were assessed and its interrelation to prefrontal cortex (PFC) activity. Support vector regression (SVR) on the resting-state ECs was used to predict prefrontal connectivity. In response to TT, EC analysis indicated modifications in the patients with PD towards the level of healthy controls during walking and at rest. SVR revealed cerebellum related connectivity patterns that were associated with the training effect on PFC. These findings suggest that the potential therapeutic effect of training on brain activity may be facilitated via changes in compensatory modulation of the cerebellar interregional connectivity.
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We aimed to quantitatively characterize progressive brain network disruption in Amyotrophic Lateral Sclerosis (ALS) during cognition using the mismatch negativity (MMN), an electrophysiological index of attention switching. We measured the MMN using 128-channel EEG longitudinally (2-5 timepoints) in 60 ALS patients and cross-sectionally in 62 healthy controls. Using dipole fitting and linearly constrained minimum variance beamforming we investigated cortical source activity changes over time. In ALS, the inferior frontal gyri (IFG) show significantly lower baseline activity compared to controls. The right IFG and both superior temporal gyri (STG) become progressively hyperactive longitudinally. By contrast, the left motor and dorsolateral prefrontal cortices are initially hyperactive, declining progressively. Baseline motor hyperactivity correlates with cognitive disinhibition, and lower baseline IFG activities correlate with motor decline rate, while left dorsolateral prefrontal activity predicted cognitive and behavioural impairment. Shorter survival correlates with reduced baseline IFG and STG activity and later STG hyperactivation. Source-resolved EEG facilitates quantitative characterization of symptom-associated and symptom-preceding motor and cognitive-behavioral cortical network decline in ALS.
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Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/psicologia , Cognição , Disfunção Cognitiva , Córtex Motor/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Estudos Transversais , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia , Prognóstico , Lobo Temporal/fisiopatologiaRESUMO
Objective.To characterize the cortical oscillations associated with performance of the sustained attention to response task (SART) and their disruptions in the neurodegenerative condition amyotrophic lateral sclerosis (ALS).Approach.A randomised SART was undertaken by 24 ALS patients and 33 healthy controls during 128-channel electroencephalography (EEG). Complex Morlet wavelet transform was used to quantify non-phase-locked oscillatory activity in event-related spectral perturbations associated with performing the SART. We investigated the relationships between these perturbations and task performance, and associated motor and cognitive changes in ALS.Main results.SART induced theta-band event-related synchronization (ERS) and alpha- and beta-band event-related desynchronization (ERD), followed by rebound beta ERS, in both Go and NoGo trials across the frontoparietal axis, with NoGo trials eliciting greater theta ERS and lesser beta ERS. Controls with greater Go trial beta ERS performed with greater speed and less accuracy. ALS patients exhibited increased anticipation compared to controls but similar reaction times and accuracy. Prefrontal (area under the receiver operating characteristic curve (AUROC) = 0.8, Cohen'sd= 0.97) and parietal (AUROC = 0.82, Cohen'sd= 1.12) beta-band ERD was significantly reduced in ALS but did not relate to performance, while patients with higher Edinburgh Cognitive and Behavioural ALS Screen (ECAS) ALS-specific scores demonstrated greater ERS in beta (rho = 0.72) upon successful withholding.Significance.EEG measurement of task-related oscillation changes reveals variation in cortical network engagement in relation to speed versus accuracy strategies. Such measures can also capture cognitive and motor network pathophysiology in the absence of task performance decline, which may facilitate development of more sensitive early neurodegenerative disease biomarkers.
Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Esclerose Lateral Amiotrófica/diagnóstico , Biomarcadores , Sincronização Cortical/fisiologia , Eletroencefalografia , Humanos , Tempo de ReaçãoRESUMO
OBJECTIVE: Poliomyelitis results in changes to the anterior horn cell. The full extent of cortical network changes in the motor physiology of polio survivors has not been established. Our aim was to investigate how focal degeneration of the lower motor neurons (LMN) in infancy/childhood affects motor network connectivity in adult survivors of polio. METHODS: Surface electroencephalography (EEG) and electromyography (EMG) were recorded during an isometric pincer grip task in 25 patients and 11 healthy controls. Spectral signal analysis of cortico-muscular (EEG-EMG) coherence (CMC) was used to identify the cortical regions that are functionally synchronous and connected to the periphery during the pincer grip task. RESULTS: A pattern of CMC was noted in polio survivors that was not present in healthy individuals. Significant CMC in low gamma frequency bands (30-47 Hz) was observed in frontal and parietal regions. CONCLUSION: These findings imply a differential engagement of cortical networks in polio survivors that extends beyond the motor cortex and suggest a disease-related functional reorganisation of the cortical motor network. SIGNIFICANCE: This research has implications for other similar LMN conditions, including spinal muscular atrophy (SMA). CMC has potential in future clinical trials as a biomarker of altered function in motor networks in post-polio syndrome, SMA, and other related conditions.