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Authors: Fecteau, Shirley | Pascual-Leone, Alvaro | Théoret, Hugo

Article Type: Research Article

Abstract: Transcranial magnetic stimulation (TMS)-induced virtual lesions in healthy subjects can be used to test neurofunctional models of disease. The interhemispheric rivalry model of heminglect is well suited for such investigations, as simple predictions derived from clinical data can be tested without the caveats normally associated with lesion studies. One of these predictions is that release from contralateral inhibition should lead to increased parietal responsiveness, which, in turn, would enhance spatial attention. Here, we detail studies showing TMS-induced paradoxical functional facilitation of attention in healthy individuals and highlight their contribution to the understanding and treatment of neglect syndromes.

Citation: Behavioural Neurology, vol. 17, no. 3-4, pp. 159-162, 2006

Authors: Menardi, Arianna | Pascual-Leone, Alvaro | Fried, Peter J. | Santarnecchi, Emiliano

Article Type: Review Article

Abstract: Comforts in modern society have generally been associated with longer survival rates, enabling individuals to reach advanced age as never before in history. With the increase in longevity, however, the incidence of neurodegenerative diseases, especially Alzheimer’s disease, has also doubled. Nevertheless, most of the observed variance, in terms of time of clinical diagnosis and progression, often remains striking. Only recently, differences in the social, educational and occupational background of the individual, as proxies of cognitive reserve (CR), have been hypothesized to play a role in accounting for such discrepancies. CR is a well-established concept in literature; lots of studies have …been conducted in trying to better understand its underlying neural substrates and associated biomarkers, resulting in an incredible amount of data being produced. Here, we aimed to summarize recent relevant published work addressing the issue, gathering evidence for the existence of a common path across research efforts that might ease future investigations by providing a general perspective on the actual state of the arts. An innovative model is hereby proposed, addressing the role of CR across structural and functional evidences, as well as the potential implementation of non-invasive brain stimulation techniques in the causal validation of such theoretical frame. Show more

Keywords: Aging, Alzheimer’s disease, cognitive reserve, diffusion tensor imaging, electroencephalography, functional magnetic resonance imaging, magnetic resonance imaging, positron emission tomography, transcranial magnetic stimulation

DOI: 10.3233/JAD-180549

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1341-1362, 2018

Authors: Carey, James R. | Fregni, Felipe | Pascual-Leone, Alvaro

Article Type: Research Article

Abstract: Purpose. This study explored the effects of motor learning training combined with repetitive transcranial magnetic stimulation (rTMS) on motor performance in healthy subjects. Methods. Twenty-seven right-handed subjects were randomized to three groups: ipsilateral rTMS (IS group), contralateral rTMS (CS group), and sham rTMS (SS group). rTMS was applied for 10 minutes (1 Hz, 90% motor threshold) prior to training. Training involved 10 minutes of finger tracking with the right hand. Tracking performance was tested before, during and after training. Results. Improvement in tracking performance over the posttests was not significantly different between the CS and SS groups, whereas it was …significantly lower for the IS group compared to the SS group. No difference was found across groups at retention tests. Conclusion. These findings indicate that rTMS interfered with motor performance transiently when applied ipsilateral to the training hand and had no effect when applied contralaterally. These results invite further work to determine whether the disruptive effect of ipsilateral rTMS observed here in healthy subjects, with presumably balanced interhemispheric inhibition, might translate differently to subjects with abnormal interhemispheric inhibition (stroke patients) in a way that disinhibits the ipsilesional hemisphere and improves performance in the paretic hand. Show more

Keywords: Repetitive transcranial magnetic stimulation, motor cortex, motor learning, interhemispheric inhibition

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 3, pp. 191-199, 2006

Authors: Walsh, Vincent | Desmond, John E. | Pascual-Leone, Alvaro

Article Type: Other

Citation: Behavioural Neurology, vol. 17, no. 3-4, pp. 131-134, 2006

Authors: Tremblay, Sara | Vernet, Marine | Bashir, Shahid | Pascual-Leone, Alvaro | Théoret, Hugo

Article Type: Research Article

Abstract: Purpose: Recent studies investigating the effects of mild traumatic brain injury (mTBI) suggest the presence of unbalanced excitatory and inhibitory mechanisms within primary motor cortex (M1). Whether these abnormalities are associated with impaired synaptic plasticity remains unknown. Methods: The effects of continuous theta burst stimulation (cTBS) on transcranial magnetic stimulation-induced motor evoked potentials (MEPs) were assessed on average two weeks and six weeks following mTBI in five individuals. Results: The procedure was well-tolerated by all participants. Continuous TBS failed to induce a significant reduction of MEP amplitudes two weeks after the injury, but response to cTBS normalized six weeks following …injury, as a majority of patients became asymptomatic. Conclusions: These preliminary results suggest that cTBS can be used to assess M1 synaptic plasticity in subacute phase following mTBI and may provide insights into neurobiological substrates of symptoms and consequences of mTBI. Show more

Keywords: Traumatic brain injury, concussion, transcranial magnetic stimulation, plasticity, motor cortex

DOI: 10.3233/RNN-140459

Citation: Restorative Neurology and Neuroscience, vol. 33, no. 5, pp. 611-620, 2015

Authors: Chang, Won Hyuk | Uhm, Kyeong Eun | Shin, Yong-Il | Pascual-Leone, Alvaro | Kim, Yun-Hee

Article Type: Research Article

Abstract: Background and Purpose: High-frequency repetitive transcranial magnetic stimulation (rTMS) aids motor recovery in patients with subacute stroke. However, the response to high-frequency rTMS is highly variable between patients. The aim of this study was to identify the factors associated with improved motor function in response to high-frequency rTMS in subacute stroke patients with moderate to severe upper extremity motor involvement. Methods: Sixty-two patients with subacute stroke were enrolled. rTMS was applied over the primary motor cortex of the affected hemisphere at 10 Hz with 1,000 pulses/day for 10 days. Upper limb motor function was scored with the upper limb of Fugl-Meyer …Assessment (FMA-UL) score before intervention and immediately after intervention. All FMA-UL changes greater than or equal to 5 points were considered clinically significant. Potential influencing factors considered included patient characteristics, motor function, corticospinal tract (CST) integrity assessments, and genetics. Multivariate logistic regression analysis was used to identify the significance of each of these factors. Results: We found that the two factors with the greatest impact on the improvement in FMA-UL score were: 1) the functional integrity of the CST, and 2) the brain-derived neurotrophic factor (BDNF) genotype (p  < 0.05). Age tended to influence clinically significant changes in the FMA-UL score, although this effect was not significant. Conclusion: Our findings suggest that high-frequency rTMS interventions aimed at improving upper extremity motor function in patients with subacute stroke with moderate to severe motor involvement should be individually tailored according to functional CST status and BDNF genotype. Show more

Keywords: Transcranial magnetic stimulation, rTMS, motor recovery, BDNF, cortical excitability, stroke

DOI: 10.3233/RNN-150634

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 5, pp. 747-755, 2016

Authors: Buss, Stephanie S. | Padmanabhan, Jaya | Saxena, Sadhvi | Pascual-Leone, Alvaro | Fried, Peter J.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) and type 2 diabetes (T2DM) are common causes of cognitive decline among older adults and share strong epidemiological links. Distinct patterns of cortical atrophy are observed in AD and T2DM, but robust comparisons between structure-function relationships across these two disease states are lacking. Objective: To compare how atrophy within distributed brain networks is related to cognition across the spectrum of cognitive aging. Methods: The relationship between structural MRI changes and cognition was studied in 22 mild-to-moderate AD, 28 T2DM, and 27 healthy participants. Cortical thickness measurements were obtained from networks of interest (NOIs) matching the limbic, …default, and frontoparietal resting-state networks. Composite cognitive scores capturing domains of global cognition, memory, and executive function were created. Associations between cognitive scores and the NOIs were assessed using linear regression, with age as a covariate. Within-network General Linear Model (GLM) analysis was run in Freesurfer 6.0 to visualize differences in patterns of cortical atrophy related to cognitive function in each group. A secondary analysis examined hemispheric differences in each group. Results: Across all groups, cortical atrophy within the limbic NOI was significantly correlated with Global Cognition (p = 0.009) and Memory Composite (p = 0.002). Within-network GLM analysis and hemispheric analysis revealed qualitatively different patterns of atrophy contributing to cognitive dysfunction between AD and T2DM. Conclusion: Brain network atrophy is related to cognitive function across AD, T2DM, and healthy participants. Differences in cortical atrophy patterns were seen between AD and T2DM, highlighting neuropathological differences. Show more

Keywords: Alzheimer’s disease, cognitive aging, dementia, diabetes mellitus, executive function, memory disorders

DOI: 10.3233/JAD-180570

Citation: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1301-1312, 2018

Authors: Bashir, Shahid | Vernet, Marine | Yoo, Woo-Kyoung | Mizrahi, Ilan | Theoret, Hugo | Pascual-Leone, Alvaro

Article Type: Research Article

Abstract: Purpose: Even after a mild traumatic brain injury (TBI) symptoms may be long lasting and never resolve completely. The neurophysiologic substrate for such lasting deficits remains unclear. There is a lack of objective measures of early brain abnormalities following mild TBI, which could shed light on the genesis of these lasting impairments. Methods: Here we report findings in a previously healthy man tested 2 and 6 weeks after a well-documented concussion. Findings were compared with 12 control subjects. All subjects underwent brain magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI). Testing included neuropsychological evaluation and physiological assessment with TMS and …EEG, excitatory/inhibitory balance and brain plasticity. Results: While the MRI, DTI and neuropsychological evaluations showed no abnormalities, neurophysiologic tests revealed subclinical abnormalities in our patient: (1) Significantly higher intracortical facilitation than the control group at both time points; (2) Intracortical inhibition presumably mediated by GABAB receptors was absent at week 2, but returned to normal value at week 6; (3) Abnormal mechanisms of plasticity at week 2, that normalize at week 6. Conclusions: These findings demonstrate a transient alteration of brain cortical physiology following concussion independent of anatomical findings and neuropsychological function. This case study suggests that TMS measures may serve as sensitive biomarkers of physiologic brain abnormalities after concussion. Show more

Keywords: Theta burst stimulation, motor cortex, excitability, EEG

DOI: 10.3233/RNN-2012-110207

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 277-282, 2012

Authors: Boggio, Paulo S. | Nunes, Alice | Rigonatti, Sergio P. | Nitsche, Michael A. | Pascual-Leone, Alvaro | Fregni, Felipe

Article Type: Research Article

Abstract: Purpose: Recent evidence has suggested that a simple technique of noninvasive brain stimulation – transcranial direct current stimulation (tDCS) – is associated with a significant motor function improvement in stroke patients. Methods: We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. Results: There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement …after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (p< 0.0001) that lasted for 2 weeks after treatment. Conclusions: The findings of our study support previous research showing that tDCS is significantly associated with motor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non-expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke. Show more

Keywords: Rehabilitation, transcranial direct current stimulation, brain DC polarization

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 2, pp. 123-129, 2007

Authors: Demirtas-Tatlidede, Asli | Alonso-Alonso, Miguel | Shetty, Ravi P. | Ronen, Itamar | Pascual-Leone, Alvaro | Fregni, Felipe

Article Type: Research Article

Abstract: Background: Contralesional hemispheric repetitive transcranial magnetic stimulation (rTMS) may improve motor function in mild to moderate stroke and effects are considered to be mediated through transcallosal motor fibers. Objective: This study aimed to investigate the safety of contralesional rTMS in a selected group of severe chronic stroke patients. Methods: Ten sessions of 1 Hz rTMS were applied to contralesional primary motor cortex (M1) using neuronavigated stimulation and changes in motor impairment were evaluated before, during and after rTMS applications and at 4-weeks follow-up. Neurophysiological response to stimulation was assessed through cortical excitability evaluations. The relationship between functional and neurophysiological response …to rTMS and microstructural integrity of transcallosal motor fibers were searched using diffusion tensor imaging (DTI) based fractional anisotropy (FA). Results: rTMS was well-tolerated with high compliance and no dropouts; no seizures or motor worsening occurred. Transcallosal FA values revealed a positive linear relationship with the mild motor improvement detected after rTMS while higher FA values were observed in subjects with better motor outcome. Cortical excitability showed a significant change in contralesional short-interval intracortical inhibition indicating altered plasticity following rTMS. Conclusions: Our results suggest that noninvasive neuromodulation of the contralesional hemisphere may present a possibility to assist adaptive neuroplastic changes in severe chronic stroke. Implementation of DTI-derived measures of transcallosal microstructural integrity may allow for individually-tailored interventions to guide processes of interhemispheric neuroplasticity. Further research is warranted to establish the clinical value of these findings in neurorehabilitation settings for subjects with chronic severe stroke. Show more

Keywords: Severe stroke, cerebrovascular disease, repetitive transcranial magnetic stimulation (rTMS), diffusion tensor imaging (DTI), neurorehabilitation, cortical excitability

DOI: 10.3233/NRE-141191

Citation: NeuroRehabilitation, vol. 36, no. 1, pp. 51-59, 2015