Bradykinesia and Its Progression Are Related to Interhemispheric Beta Coherence.

OBJECTIVE: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction. METHODS: Twenty-one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN-STN beta coherence. RESULTS: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN-STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia. INTERPRETATION: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029-1039.

Study of neuropathological changes and dementia in 100 centenarians in The 90+ Study.

INTRODUCTION: The association between neuropathological changes and dementia among centenarians and nonagenarians remains unclear. METHODS: We examined brain tissue from 100 centenarians and 297 nonagenarians from The 90+ Study, a community-based longitudinal study of aging. We determined the prevalence of 10 neuropathological changes and compared their associations with dementia and cognitive performance between centenarians and nonagenarians. RESULTS: A total of 59% of centenarians and 47% of nonagenarians had at least four neuropathological changes. In centenarians, neuropathological changes were associated with higher odds of dementia and, compared to nonagenarians, the odds were not attenuated. For each additional neuropathological change, the Mini-Mental State Examination score was lower by 2 points for both groups. DISCUSSION: Neuropathological changes continue to be strongly related to dementia in centenarians, highlighting the importance of slowing or preventing the development of multiple neuropathological changes in the aging brain to maintain cognitive health. HIGHLIGHTS: Individual and multiple neuropathological changes are frequent in centenarians. These neuropathological changes are strongly associated with dementia. There is no attenuation of this association with age.

Abdominal Tremor in Idiopathic Parkinson's Disease: A Case Report.

Background: Tremor in Parkinson's disease (PD) is commonly seen in the upper extremities and can involve the lower extremities and mouth. We present a case of a patient with idiopathic PD who presented with abdominal tremor. Case Report: A 40-year-old man with a 2-year history of subjective weakness and stiffness in the right arm and leg, followed by emergence of a right hand tremor, subsequently developed abdominal tremor. Patient experienced marked improvement of both abdominal and hand tremor and mobility of the right limbs with levodopa. Discussion: Our case report serves as the second only published report of abdominal tremor in an idiopathic PD patient. Highlights: Tremor in Parkinson's disease (PD) commonly affects the upper and lower extremities and mouth. We describe a 40-year-old man with PD who developed abdominal tremor which was brought under control with levodopa. This case is one of only two published reports of abdominal tremor in PD.

Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.

Background: Resting state beta band (13-30 Hz) oscillations represent pathological neural activity in Parkinson's disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states. Methods: Subthalamic (STN) and local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa® PC + S, Medtronic PLC.) in fourteen PD participants (six tremor-dominant and eight akinetic-rigid) off medication/off STN DBS during 30 s of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups. Results: Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group. Conclusion: The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.

Lack of progression of beta dynamics after long-term subthalamic neurostimulation.

OBJECTIVE: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). METHODS: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale - motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. RESULTS: After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score. INTERPRETATION: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.