Neuroimaging of Parkinson's

Official title

Precision Neuroimaging of Parkinson's Disease

Overview

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.

Detailed description

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.

Primary outcome measures

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

Secondary outcome measures (1)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United States · 1 center

• East Imaging Building — St Louis

Publications

• Cui W, Wang Y, Ren J, Hubbard CS, Fu X, Fang S, Wang D, Zhang H, Li Y, Li L, Jiang T, Liu H. Personalized fMRI Delineates Functional Regions Preserved within Brain Tumors. Ann Neurol. 2022 Mar;91(3):353-366. doi: 10.1002/ana.26303. Epub 2022 Jan 31. PMID 35023218
• Ren J, Chi Q, Hubbard CS, Cui W, Wang D, Li L, Zhang H, Liu H. Personalized functional imaging identifies brain stimulation target for a patient with trauma-induced functional disruption. Brain Stimul. 2022 Jan-Feb;15(1):53-56. doi: 10.1016/j.brs.2021.11.005. Epub 2021 Nov 5. No abstract available. PMID 34749006
• Guo Y, Ren J, Cui W, Dahmani L, Wang D, Fu X, Li M, Li S, Zhang Y, Lin X, Zhen Z, Xu Y, Xie D, Guan H, Yi F, Wang J, Shi Q, Liu H. Personalized brain MRI revealed distinct functional and anatomical disruptions in Creutzfeldt-Jakob disease and Alzheimer's disease. CNS Neurosci Ther. 2024 Feb;30(2):e14404. doi: 10.1111/cns.14404. Epub 2023 Aug 14. PMID 37577861
• Dahmani L, Bai Y, Li M, Ren J, Shen L, Ma J, Li H, Wei W, Li P, Wang D, Du L, Cui W, Liu H, Wang M. Focused ultrasound thalamotomy for tremor treatment impacts the cerebello-thalamo-cortical network. NPJ Parkinsons Dis. 2023 Jun 15;9(1):90. doi: 10.1038/s41531-023-00543-8. PMID 37322044
• Ji GJ, Liu T, Li Y, Liu P, Sun J, Chen X, Tian Y, Chen X, Dahmani L, Liu H, Wang K, Hu P. Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease. Hum Brain Mapp. 2021 Apr 15;42(6):1670-1681. doi: 10.1002/hbm.25319. Epub 2020 Dec 14. PMID 33314545
• Hill KK, Campbell MC, McNeely ME, Karimi M, Ushe M, Tabbal SD, Hershey T, Flores HP, Hartlein JM, Lugar HM, Revilla FJ, Videen TO, Earhart GM, Perlmutter JS. Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson's disease. Exp Neurol. 2013 Mar;241:105-12. doi: 10.1016/j.expneurol.2012.12.003. Epub 2012 Dec 19. PMID 23262122
• Myers PS, McNeely ME, Koller JM, Earhart GM, Campbell MC. Cerebellar Volume and Executive Function in Parkinson Disease with and without Freezing of Gait. J Parkinsons Dis. 2017;7(1):149-157. doi: 10.3233/JPD-161029. PMID 28106569
• 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

Identifiers

NCT: NCT07024875 · 202410006 · R01NS140256

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗