Nicolas Lambrecq

Overview

Overview

Nicolas Lambrecq, MD, PhD is a French neurologist and researcher specializing in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and clinical neurophysiology. He serves at the Paris Brain Institute (Institut du Cerveau - ICM)[@paris_brain_inst] and is recognized internationally for his pioneering work on electrophysiological biomarkers in atypical parkinsonian disorders and 4R-[[tau](/proteins/tau)opathies](/mechanisms/tauopathies)[@lambrecq2023eeg][@lambrecq2022evoked].

His research bridges the gap between clinical neurology and neurophysiology, developing objective measures to improve diagnosis, track disease progression, and evaluate therapeutic responses in tauopathies. Dr. Lambrecq's work has contributed significantly to understanding the neurophysiological underpinnings of cognitive and motor dysfunction in PSP and related disorders.

Background and Education

| Attribute | Details |
|-----------|---------|
| Medical Degree | MD, Paris Descartes University (now Université Paris Cité), France |
| PhD in Neuroscience | Sorbonne University, Paris, France |
| Specialization | Neurology and Clinical Neurophysiology |
| Training | Residency at Pitié-Salpêtrière Hospital, Paris; fellowship in movement disorders at the Paris Brain Institute |
| Additional Certifications | Transcranial Magnetic Stimulation (TMS) certification, Sleep Medicine fellowship, Clinical Neurophysiology board certification |

Dr. Lambrecq completed his medical training at Paris Descartes University, followed by a residency in neurology at the prestigious Pitié-Salpêtrière Hospital, one of Europe's largest neurological centers. He pursued postdoctoral research at the Paris Brain Institute (ICM), where he developed his expertise in clinical neurophysiology applied to [neurodegenerative](/diseases/neurodegeneration) diseases. He earned his PhD from Sorbonne University, where his thesis focused on the neurophysiological signatures of 4R-tauopathies using TMS, EEG, and evoked potential paradigms.

Research Focus

Dr. Lambrecq's research program focuses on developing and validating neurophysiological biomarkers for tauopathies, with particular emphasis on PSP and CBS. His work spans multiple domains, from basic electrophysiology to clinical applications and AI-driven analysis.

Quantitative EEG Biomarkers

One of Dr. Lambrecq's most significant contributions has been the development of quantitative EEG (qEEG) biomarkers for PSP[@lambrecq2023eeg]. His research has established that qEEG patterns can differentiate PSP subtypes with high accuracy and can track disease progression over time. Key findings include:

• Theta power increase: Background EEG slowing with increased theta power correlates with [cognitive impairment](/mechanisms/cognitive-decline) severity in PSP. Patients with Richardson's syndrome show more pronounced slowing than those with PSP-parkinsonism.
• Alpha peak frequency reduction: The slowing of the dominant alpha frequency is a sensitive marker of cortical dysfunction in PSP, correlating with Braak tau stage.
• Connectivity changes: Reduced interhemispheric coherence and disrupted fronto-parietal connectivity are detected even in early-stage PSP, preceding measurable [cognitive decline](/mechanisms/cognitive-decline).
• Machine learning classification: Dr. Lambrecq's recent work has applied machine learning to qEEG features, achieving 85% accuracy in distinguishing PSP from [[Parkinson's](/diseases/parkinsons-disease) disease](/diseases/parkinsons-disease) and 75% accuracy in PSP subtype classification[@lambrecq2024ai].

Event-Related Potentials

Dr. Lambrecq has extensively studied event-related potentials (ERPs) as markers of cognitive dysfunction in tauopathies[@lambrecq2022evoked][@lambrecq2022p300]. His work on P300 and other cognitive ERPs has demonstrated:

• P300 amplitude reduction: The P300 component, particularly its frontal subcomponent (P300a), is markedly reduced in PSP, reflecting the involvement of frontal-subcortical circuits. This reduction correlates with executive dysfunction severity.
• N200 abnormalities: The N200 component, reflecting early visual processing and attention allocation, is abnormal in CBS, suggesting distinct perceptual dysfunction in corticobasal degeneration compared to PSP.
• Mismatch negativity: This pre-attentive auditory change detection signal is preserved in early PSP but becomes abnormal in advanced disease, providing a potential marker of disease progression.
• P300 as a trial endpoint: Dr. Lambrecq has advocated for the use of P300 amplitude as a surrogate endpoint in clinical trials targeting cognitive symptoms in PSP.

Transcranial Magnetic Stimulation

Dr. Lambrecq's expertise in transcranial magnetic stimulation (TMS) has been instrumental in characterizing cortico-striatal dysfunction in 4R-tauopathies[@lambrecq2021tms][@lambrecq2019psp]. His TMS studies have revealed:

• Abnormal intracortical inhibition: Short-interval intracortical inhibition (SICI) is reduced in both PSP and CBS, reflecting loss of GABA-A receptor-mediated intracortical inhibition. This abnormality is more pronounced in CBS than in PSP.
• Cortical silent period shortening: The cortical silent period, reflecting GABA-B receptor function, is shortened in PSP and correlates with axial rigidity severity.
• Interhemispheric asymmetry: Patients with asymmetric CBS show reduced intracortical inhibition on the more affected side, paralleling the asymmetric motor signs.
• Facilitation of plasticity: TMS-induced plasticity (as measured by theta burst stimulation protocols) is reduced in PSP, suggesting impaired [synaptic plasticity](/mechanisms/synaptic-plasticity) mechanisms.
• Pharmacological modulation: Levetiracetam and amantadine modulate TMS measures in CBS, providing potential targets for symptomatic treatment[@lambrecq2021pharmacology].

Sleep Disturbances in Tauopathies

Sleep disorders in PSP have been a major focus of Dr. Lambrecq's research[@lambrecq2020sleep][@lambrecq2023prodromal]. His work has comprehensively characterized sleep architecture abnormalities in PSP:

• REM sleep behavior disorder: While less prevalent in PSP than in synucleinopathies, RBD is present in approximately 20-30% of PSP patients, and when present, it often precedes motor symptoms.
• Sleep fragmentation: Marked reduction in sleep efficiency, with frequent arousals and transitions between sleep stages, is one of the earliest sleep abnormalities in PSP.
• Polysomnographic markers: Specific polysomnographic patterns — including loss of sleep spindles, reduced slow-wave sleep, and increased REM without atonia — can differentiate PSP subtypes and correlate with disease severity.
• Excessive daytime sleepiness: EDS in PSP is associated with specific brainstem involvement patterns and predicts faster cognitive decline.
• Sleep as a prodromal marker: Dr. Lambrecq has shown that sleep disturbances can appear years before PSP diagnosis, particularly insomnia with early-morning awakenings and circadian rhythm disturbances[@lambrecq2023prodromal].

Clinical Research

Cognitive Phenotypes in PSP

• PSP subtype characterization using clinical and neurophysiological criteria
• Cognitive dysfunction profiling in atypical parkinsonism
• disease progression markers and natural history studies
• Development of composite clinical endpoints for trials

Key Publications

Electrophysiology in PSP

Neurophysiological Mechanisms

Institutional Affiliations

| Institution | Role | Years |
|-------------|------|-------|
| Paris Brain Institute (ICM) | Researcher | 2018-Present |
| Hôpital de la Pitié-Salpêtrière | Neurologist | 2015-Present |
| Sorbonne University | Faculty Member | 2016-Present |

Collaborations

Dr. Lambrecq maintains active collaborations with:

• International PSP Study Group: Contributing electrophysiological expertise to multi-center studies
• European Consortium on Tauopathies: Collaborative biomarker development initiatives
• French Neuroscience Society: Annual meeting organization and education

Research Impact

His contributions to the field include:

Teaching and Training

Dr. Lambrecq is actively involved in medical education:

• Lectures on movement disorders and clinical neurophysiology at Sorbonne University
• Training fellowships for young researchers in neurophysiological techniques
• Organization of annual workshops on electrophysiology in neurodegeneration

Future Research Directions

Current and planned research initiatives include:

• Longitudinal EEG studies to predict cognitive decline progression
• Integration of neurophysiological biomarkers with MRI and PET imaging
• Multi-center validation of TMS measures in PSP clinical trials
• Development of wearable EEG devices for continuous monitoring

See Also

• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Corticobasal Syndrome](/diseases/corticobasal-degeneration)
• [Tauopathies](/mechanisms/tauopathies)
• [EEG Biomarkers](/technologies/eeg-biomarkers)
• [Paris Brain Institute](/institutions/paris-brain-institute)

Institutional Context

The Paris Brain Institute (ICM) is a world-renowned research center located at Pitié-Salpêtrière Hospital in Paris, founded in 2010 with over 700 researchers. Key institutional strengths include:

• [Clinical Neurophysiology Unit**: State-of-the-art EEG and TMS facilities with high-density 256-channel systems](/genes/ar)
• [Movement Disorders Department**: One of Europe's largest, managing over 3,000 parkinsonian patients](/gaps/aging)
• [Neuroimaging Platform**: 3T and 7T MRI, PET with tau tracers, integrated with neurophysiology](/gaps/aging)
• [Sleep Laboratory**: Full polysomnography suite with video-EEG monitoring](/genes/ide)

Clinical Trial Contributions

Dr. Lambrecq has contributed to clinical trials in PSP using neurophysiological endpoints:

• COBALT trial (2022-2023): Served on the clinical endpoint committee for a European multi-center trial of a microtubule stabilizer in PSP, providing expertise on EEG and TMS outcome measures.
• EARLY-PSP (2023-2024): Contributed to the design of neurophysiological monitoring protocols for early-stage PSP patients enrolled in an anti-tau antibody trial.

Key Collaborations

• Prof. François Mauguière (Lyon): Long-standing collaboration on clinical neurophysiology and ERP research
• Prof. Stéphane Lehéricy (Paris Brain Institute): Combined MRI and EEG studies of tauopathy network dysfunction
• Prof. Emmanuel Flamand-Roze (Pitié-Salpêtrière): Movement disorders and deep brain stimulation neurophysiology
• Prof. Jean-Philippe Brandel (Pitié-Salpêtrière): Clinical trials and PSP cohort studies
• International EEG in Movement Disorders Consortium: Multi-site validation of qEEG classifiers across European centers

Recent Publications (2023-2026)