Abstract
INTRODUCTION
We examined how abnormal prefrontal neurophysiology and changes in gamma-aminobutyric acid-ergic (GABAergic) neurotransmission contribute to behavioral impairments in disorders associated with frontotemporal lobar degeneration (FTLD).
METHODS
We recorded magnetoencephalography during an adaptive visuomotor task from 11 people with behavioral-variant frontotemporal dementia, 11 with progressive supranuclear palsy, and 20 age-matched controls. We used tiagabine, a gamma-aminobutyric acid (GABA) re-uptake inhibitor, as a pharmacological probe to assess the role of GABA during motor-related beta power changes.
RESULTS
Task impairments were associated with diminished movement-related beta power. Tiagabine facilitated partial recovery of behavioral impairments and neurophysiology, moderated by executive function, such that the greatest improvements were seen in those with higher cognitive scores. The right prefrontal cortex was revealed as a key site of drug interaction.
DISCUSSION
Behavioral and neurophysiological deficits can be mitigated by enhancement of GABAergic neurotransmission. Clinical trials are warranted to test for enduring clinical benefits from this restorative-psychopharmacology strategy.
Highlights
Event-related beta power changes during movement can be altered by the GABA reuptake inhibitor, tiagabine.
In people with behavioral-variant frontotemporal dementia and progressive supranuclear palsy, tiagabine enhanced beta modulation and concurrently improved task performance, dependent on baseline cognition, and diagnosis.
The effects of the drug suggest a GABA-dependent beta-related mechanism that underlies adaptive motor control.
Restoring selective deficits in neurotransmission is a potential means to improve behavioral symptoms in patients with dementia.
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This post is Copyright: Laura E. Hughes,
Natalie E. Adams,
Matthew A. Rouse,
Michelle Naessens,
Alexander Shaw,
Alexander G. Murley,
Thomas E. Cope,
Negin Holland,
David Nesbitt,
Duncan Street,
David J. Whiteside,
James B. Rowe | February 19, 2025