Neuroimaging of Parkinson's

Официальное название

Precision Neuroimaging of Parkinson's Disease

Обзор

Parkinson's Disease (PD) is a neurodegenerative disorder caused by dysfunction in both subcortical structures and the cortex. The investigators recently discovered a new brain system called the Somato-Cognitive Action Network (SCAN), which could be a primary locus of dysfunction in PD. Here, the investigators will use magnetic resonance imaging techniques in PD patients to test whether SCAN is critical for PD. The investigators will determine whether SCAN is connected to PD-relevant subcortical structures, and whether PD patients exhibit altered subcortical-to-SCAN connectivity. If successful, this work will identify SCAN as a specific circuit altered in PD patients that can serve as a new target for future neuromodulatory PD therapies.

Подробное описание

Parkinson's Disease (PD) is a neurodegenerative disease that causes symptoms such as tremor, bradykinesia, and freezing of gait, as well as sleep disturbance, autonomic dysfunction, and abulia. PD patients particularly struggle to initiate and maintain actions, which causes gait freezing, leading to falls. PD results from dysfunction in motor circuitry, including connections between subcortical structures such as substantia nigra and striatum, as well as primary motor cortex, which drives voluntary movement.

Recently, our group rewrote the textbook diagrams of motor circuitry. The investigators described a previously unrecognized Somato-Cognitive Action Network (SCAN) which is interspersed between effector-specific regions of primary motor cortex (foot, hand, mouth). The SCAN is engaged by coordinated rather than isolated actions, and it is strongly preferentially connected to other cortical regions important for action planning and control, autonomic function, and arousal.

Many SCAN functions (drive to act, gait, autonomic control, arousal, motor coordination) are affected in PD. Further, clinical targets for neuromodulation in PD are connected to SCAN. Thus, SCAN dysfunction might be an important aspect of PD pathophysiology and resulting symptoms. Critically, recent technical advances in noninvasive functional neuroimaging allow us for the first time to reliably evaluate the connectivity of motor systems, including SCAN, into the deep subcortical structures most relevant for PD.

Using these patient-oriented techniques, the investigators will first test whether PD-relevant subcortical structures-including clinical targets for PD-are connected more strongly to the SCAN circuit than to effector-specific M1 foot, hand, and mouth regions. The investigators will then test whether these subcortical-to-SCAN circuits are altered in PD patients to a greater degree than effector-specific circuits.

This work will advance a new conceptualization of PD as a disorder of SCAN rather than of traditional effector-specific M1, which will revolutionize how the investigators think of the disorder. Localizing PD disruption to specific portions of M1 could aid with evaluation of patients using these advanced, noninvasive fMRI techniques, and can provide precision targets of interest for other imaging modalities. Noninvasive mapping of cortico-subcortical connectivity will enable optimal target definition for neuromodulatory treatment of PD. Reconceptualizing PD as a disorder of SCAN, a system for integrated action, rather than of M1 circuits for isolated movement, may spur development of alternate symptom evaluation tools oriented around this framework. Finally, localizing M1 sites of disruption in PD opens the possibility of treating PD using cortical stimulation, a less-invasive alternative to deep brain stimulation.

Первичные конечные точки

• Cortico-subcortical connectivity to SCAN vs effectors [Срок оценки: 6 months per participant; 3-4 sessions for controls, 6-8 sessions for PD patients]

Вторичные конечные точки (1)

• Cortico-subcortical connectivity to SCAN in Parkinson's and controls [Срок оценки: 6 months per participant; 3-4 sessions for controls, 6-8 sessions for PD patients]

Критерии участия

Критерии включения

• Must meet specific health and cognitive criteria depending on the group. For PD participants
• Clinical diagnosis of Parkinson's Disease
• Must not meet dementia criteria For Healthy Control Participants
• Normal or benign neurological exam
• Normal cognition
• No first-degree relatives with Parkinson's Disease

Критерии исключения

• Neurological Disorders (other than PD)

\- Any other neurological condition

• Significant Head Injury

• Head injury with loss of consciousness >5 minutes
• Or any neurological sequelae
• Psychiatric Disorders

• Schizophrenia
• Bipolar Disorder
• Epilepsy
• Serious Medical Conditions

• End-stage organ failure
• Ongoing cancer treatment
• Cognitive Impairment

• Diagnosis of dementia
• MMSE score <24 or MoCA score <21
• MRI contraindications

• Metal implants
• claustrophobia
• Weight over 300 lbs (due to weight restrictions of the MRI scanner)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• East Imaging Building — St Louis

Публикации

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• Horin AP, Myers PS, Pickett KA, Earhart GM, Campbell MC. Resting-state functional connectivity associated with gait characteristics in people with Parkinson's disease. Behav Brain Res. 2021 Aug 6;411:113398. doi: 10.1016/j.bbr.2021.113398. Epub 2021 Jun 2. PMID 34087255

Идентификаторы

NCT: NCT07024875 · 202410006 · R01NS140256

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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