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Alvaro Pascual-Leone

Alvaro Pascual-Leone
Harvard Medical School, Boston, MA, United States · Neurology

MD, PhD

About

1,192
Publications
272,546
Reads
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103,287
Citations
Additional affiliations
August 2019 - present
Hebrew SeniorLife
Position
  • Senior Researcher
August 2019 - present
Hebrew SeniorLife
Position
  • Managing Director
January 1997 - August 2019
Beth Israel Deaconess Medical Center & Harvard Medical School
Position
  • Managing Director
Description
  • www.tmslab.org

Publications

Publications (1,192)
Article
Full-text available
In recent years, supported by new scientific evidence, the conceptualization of cognitive reserve (CR) has been progressively enriched and now encompasses not only cognitive stimulating activities or educational level, but also lifestyle activities, such as leisure physical activity and socialization. In this context, there is increasing interest i...
Article
Full-text available
Introduction: The prefrontal cortex (PFC) plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this stu...
Article
Full-text available
Rey Auditory Verbal Learning Test (RAVLT) is an episodic memory helpful measure to detect changes associated with abnormal aging. There is a lack of RAVLT validation and normalization studies in Spain. The aim was to determine its psychometric properties and explore long-term forgetting (LTF) performance through 1-week delayed recall under three di...
Article
Full-text available
Brain health is essential to successful aging, and exercise is essential to brain health. Evidence supports the benefits of regular physical and cognitive exercise in preventing or delaying progressin of mild cognitive impairment and dementia. Despite known benefits, motivation to initiate and adhere to an exercise program can be challenging to old...
Article
Full-text available
Age-related cognitive impairment (ARCI) has a profound impact on individuals, families, health care systems, and societies at large. Evidence suggests that ARCI is the consequence of underlying brain pathology. Therefore, efforts to minimize the impact of ARCI and thus closing the gap between health span and life span, which has widened in recent y...
Article
Full-text available
Chronic pain is associated with worse mental health and cognitive impairment, which can be a cause or a consequence of brain structure and function alterations, e.g., maladaptive plasticity, antinociceptive system dysregulation. Cognitive reserve reflects the effectiveness of the internal connections of the brain and it has been shown to be a prote...
Poster
Full-text available
Loss of memory is an early and debilitating symptom in patients with Alzheimer’s Disease Related Dementia (ADRD). There are currently limited therapeutic options. Recently, we identified the dysregulation of gamma oscillations in the angular gyrus of ADRD patients as captured by high-density electroencephalography (hd-EEG) during a memory task. Her...
Article
Objective: Negative symptoms of schizophrenia are substantially disabling and treatment resistant. Novel treat- ments like repetitive transcranial magnetic stimulation (TMS) need to be examined for the same using the experimental medicine approach that incorporates tests of mechanism of action in addition to clinical efficacy in trials. Methods: St...
Preprint
Full-text available
Episodic autobiographical memory (EAM) is a complex cognitive function that emerges from the coordination of specific and distant brain regions. Specific brain rhythms, namely theta and gamma oscillations and their synchronization, are thought of as putative mechanisms enabling EAM. Yet, the mechanisms of inter-regional interaction in the EAM netwo...
Article
Full-text available
The brain regions responsible for hallucinations remain unclear. We studied 89 brain lesions causing hallucinations using a recently validated technique termed lesion network mapping. We found that hallucinations occurred following lesions to a variety of different brain regions, but these lesion locations fell within a single functionally connecte...
Article
The right hemisphere is involved with the integrative processes necessary to achieve global coherence during reasoning and discourse processing. Specifically, the right temporal lobe has been proven to facilitate the processing of distant associate relationships, such as generating novel ideas. Previous studies showed a specific swing of alpha and...
Article
Full-text available
Cognitive enhancement interventions aimed at boosting human fluid intelligence (gf) have targeted executive functions (EFs), such as updating, inhibition, and switching, in the context of transfer-inducing cognitive training. However, even though the link between EFs and gf has been demonstrated at the psychometric level, their neurofunctional over...
Article
Full-text available
Objective: To assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at γ frequency (γ-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer’s disease (MCI-AD)....
Article
Assessments of postural control provide important insights into health. We created a smartphone App-based assessment of standing posture—completed with the phone placed in the user’s pocket—to enable remote monitoring of function while minimizing the need for in-person assessment or contact. We tested the reliability of App-derived postural sway me...
Article
Full-text available
Introduction Former American style football players (ASF players) have recognized health concerns associated with prior sport participation. It remains unknown whether categorizations of current health conditions, referred in this report as afflictions (conceptually framed as neurocognitive, cardiovascular, cardiometabolic, sleep apnea, and chronic...
Article
Full-text available
OBJECTIVE: Loneliness is the subjective distress of feeling alone and has a strong impact on wellbeing and health. In addition to well-known predictors like isolation and poor health, a better understanding of the psychological determinants of loneliness would offer effective targets for future complementary interventions. METHODS: In this cross-se...
Article
We review the latest evidence from animal models, studies in humans using electrophysiology, experimental memory paradigms, and non-invasive brain stimulation (NIBS), in the form of transcranial alternating current stimulation (tACS), suggesting that the altered activity in networks that contribute to the autobiographical memory (ABM) deficits may...
Article
Full-text available
Whether antagonistic brain states constitute a fundamental principle of human brain organization has been debated over the past decade. Some argue that intrinsically anti-correlated brain networks in resting-state functional connectivity are an artifact of preprocessing. Others argue that anti-correlations are biologically meaningful predictors of...
Article
Full-text available
Social networks have broad effects on health and quality of life. Biopsychosocial factors may also modify the effects of brain trauma on clinical and pathological outcomes. However, social network characterization is missing in studies of contact sports athletes. Here, we characterized the personal social networks of former National Football League...
Article
Full-text available
Background In recent years, it has become increasingly apparent that characterizing individual brain structure, connectivity and dynamics is essential for understanding brain function in health and disease. However, the majority of neuroimaging and brain stimulation research has characterized human brain function by averaging measurements from grou...
Preprint
Full-text available
Objective Interindividual variability of single and paired-pulse TMS data has limited the clinical and experimental applicability of these methods. This study brought together over 60 TMS researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of fac...
Article
Full-text available
As in previous periods of quarantine, lockdown confinement measures dictated to control SARS-CoV-2 would be expected to negatively affect mental health. We investigated the immediate effects (over a 10 day period) of a strict nationwide stay-at-home order imposed in Spain, one of the countries most affected by the COVID-19 pandemic. Focusing our an...
Article
Full-text available
Objective: The relevance of the episodic memory in the prediction of brain aging is well known. The Face Name Associative Memory Exam (FNAME) is a valued associative memory measure related to Alzheimer’s disease (AD) biomarkers, such as amyloid-β deposition preclinical AD individuals. Previous validation of the Spanish version of the FNAME test (S-...
Article
Transcranial magnetic stimulation (TMS) reveals decreased efficacy of long-term potentiation-like (LTP-like) neuroplastic mechanisms in Alzheimer's disease (AD). However, it is not yet known whether LTP-like plasticity is also impaired in prodromal AD, or how abnormal TMS measures are related to established AD biomarkers. Here, we investigated the...
Article
Full-text available
As the field of noninvasive brain stimulation (NIBS) expands there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three differ...
Poster
Three previous studies administrated the Spanish version of the Face Name Associative Memory Exam task (S‐FNAME) to Spanish participants. Sanabria and collaborators, (2018) in their investigation on subjective cognitive decline individuals, reported associations between task performance and amyloid‐β (Aβ) burden, in accordance with the original pub...
Poster
Neurodegenerative brain changes that lead to cognitive decline generally begin decades prior to the onset of symptoms. On the other hand, brain health relates to overall, and specifically cardio‐vascular health, and vice‐versa. The objective of this investigation was to assess the relationships between two important domains of cardiovascular health...
Poster
Aging has been associated with changes in the mechanisms of brain plasticity, specifically with the reduction of motor cortex excitability and decreased effectiveness of mechanisms of cortical inhibition (Pascual‐Leone et al., 2011; Lissemore et al., 2018). Emerging evidence suggests that regular practice of physical activity, which can increase ca...
Article
Alzheimer’s disease (AD) is associated with increased cortical excitability, including a risk of seizures and epileptiform discharges. Transcranial magnetic stimulation (TMS) can be used to index cortical excitability non‐invasively, and previous studies have revealed increased TMS excitability measures in AD. However, it is not yet known if TMS sh...
Poster
Thanks to technological advances the administration of cognitive assessments via computers, tablets or smartphones continues to increase, both in research and clinical practice. Several systems are commercially available and have been validated. However, there are limited tools that provide a baseline assessment and guide a personalized training pr...
Article
Full-text available
Information processing in the brain is mediated by structural white matter pathways and is highly dependent on topological brain properties. Here we combined transcranial magnetic stimulation (TMS) with high-density electroencephalography (EEG) and Diffusion Weighted Imaging (DWI), specifically looking at macroscale connectivity to understand wheth...
Article
Importance Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not...
Article
Interhemispheric inhibition (IHI) is a dual-site TMS protocol measuring inhibitory interactions between the primary motor cortices (M1). IHI is performed by applying an initial conditioning stimulus followed by a test stimulus to the contralateral M1. Conventionally, the response in the contralateral hand to the conditioning TMS pulse is either not...
Article
Full-text available
This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical setti...
Article
Full-text available
Background Face individual identity recognition skill is heritable and independent of intellectual ability. Difficulties in face individual identity recognition are present in autistic individuals and their family members and are possibly linked to oxytocin polymorphisms in families with an autistic child. While it is reported that developmental pr...
Article
Full-text available
Objective: In this study we examined the personality profiles of adults with autism spectrum disorder (ASD) using a standard personality test. In addition, we investigated the association between ASD-related face memory deficits (FMD) and theory of mind (ToM). In a broader context, we examine whether there are distinct clinical phenotypes in the AS...
Article
Objective: To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance. Methods: Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery...
Preprint
Background: Face individual identity recognition skill is heritable and independent of intellectual ability. Difficulties in face individual identity recognition are present in autistic individuals and their family members and are possibly linked to oxytocin polymorphisms in families with an autistic child. While it is reported that developmental p...
Preprint
Full-text available
Fronto-parietal activity has been related to fluid intelligence and flexible cognitive control. However, causal insights on this relation are lacking. We used real-time integration of MRI-guided TMS and EEG to characterize the spatial and temporal properties of signal propagation between these two regions and relate them to cognitive performance. 3...
Article
Date Presented 03/26/20 We conducted a phase I pilot randomized controlled trial examining the preliminary efficacy of combining brain and hand stimulation to improve hand function in individuals with moderate to severe chronic stroke. Our findings suggest that the combined brain and hand stimulation shows promise in improving hand movement, functi...
Article
Full-text available
Background Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. Objective /Hypothesis: This study brought together over 60 TMS researchers to form the ‘Big TMS Data Collaboratio...
Poster
Background: Neurodegenerative brain changes that lead to cognitive decline generally begin decades prior to the onset of symptoms. On the other hand, brain health relates to overall, and specifically cardio-vascular health, and vice-versa. The objective of this investigation was to assess the relationships between two important domains of cardiovas...
Poster
Background: Aging has been associated with changes in the mechanisms of brain plasticity, specifically with the reduction of motor cortex excitability and decreased effectiveness of mechanisms of cortical inhibition (Pascual-Leone et al., 2011; Lissemore et al., 2018). Emerging evidence suggests that regular practice of physical activity, which can...
Article
Dynamics within and between functional resting‐state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel,...
Article
Full-text available
Objective To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for treatment of cognitive symptoms in patients with Alzheimer’s disease (AD). A secondary objective was to analyze associations between brain plasticity and cognitive effects of treatment.Methods In this randomized, sham-co...
Article
Full-text available
Purpose Race differences in health are pervasive in the United States. American-style football players are a racially diverse group with social status and other benefits that may reduce health disparities. Whether race disparities in health exist among former professional football players, and whether they differ by era of play, is unknown. Method...
Article
Objective Cathodal direct current stimulation (cDCS) induces long‐term depression (LTD)‐like reduction of cortical excitability (DCS‐LTD), which has been tested in the treatment of epilepsy with modest effects. In part, this may be due to variable cortical neuron orientation relative to the electric field. We tested, in vivo and in vitro , whether...
Article
Full-text available
Several decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and proposed as a substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to model mesoscopic ephaptic activity in the human brain and explore its trajectory during...
Article
Full-text available
Electromagnetic noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation and transcranial electrical stimulation, are widely used in research and represent emerging clinical treatment options for many brain disorders. The brain-wide neurobiological effects of electromagnetic NIBS, however, are not yet fully charact...
Preprint
Background: Advancing age affects the brain's resting-state functional networks. Combining non-invasive brain stimulation (NIBS) with neuroimaging is a promising approach to modulate activity across resting-state functional systems and explore their true contribution to cognitive function in aging. However, substantial individual variability in the...
Preprint
Full-text available
Objective. To assess the utility of the modulation of motor cortex (M1) excitability by continuous theta-burst stimulation (cTBS) as a physiologic biomarker for adults with autism spectrum disorder (ASD), and to evaluate the influences of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms on cTBS aftereffects. Method...
Article
Full-text available
Neuroimaging studies show that the brain articulatory motor system is activated during speech perception. These results, however, cannot determine whether the motor system is engaged in motor simulation (e.g., lip movement) or in non-motor computations. To gauge the causal role of the articulatory motor system, here we examine the effect of mechani...
Article
Full-text available
Objective American‐style football (ASF) has gained attention because of possible links between repetitive head injury and neurodegenerative diseases. While post‐mortem pathologic changes consistent with chronic traumatic encephalopathy (CTE) have been reported in ASF players, there are currently no established pre‐mortem diagnostic criteria for CTE...
Article
Introduction: Aerobic exercise is known to promote cognitive function and mental well-being in aging adults, but the exact mechanisms are not fully elucidated. Studies in animal models and humans have attributed exercise-mediated cognitive improvements to two main mechanisms: neuroplastic changes in the nervous system resulting in enhanced synaptic...