WIP Special

Tim den Boer, Polytimi Frangou, Camille Lasbareilles

Wednesday, 08 October 2025, 12pm to 1pm

Hybrid via Teams and in the Cowey Room, FMRIB Annexe

Hosted by Saad Jbabdi

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WIN Wednesday Works In Progress Exploring state dependency in TUS to the human primary motor cortex

Presented by Tim den Boer

Abstract: Transcranial ultrasound stimulation (TUS) is an emerging non-invasive brain stimulation technique with potential therapeutic applications. However, the optimal conditions for inducing neuroplastic changes remain unclear. Previous cellular work has demonstrated that the endogenous firing rate of neurons during TUS delivery strongly influences stimulation effects. Building on these findings, this study explores state dependency in humans by investigating how TUS effects on motor cortex excitability depend on brain state during stimulation delivery. Healthy adult participants will undergo structural and functional MRI to identify the hand motor cortex, followed by four TUS sessions using a 2×2 factorial design that crosses stimulation site (motor cortex vs. control region) and brain state (rest vs. active motor engagement). Motor cortex excitability will be assessed through transcranial magnetic stimulation (TMS) measurements of motor evoked potentials, alongside behavioral tasks evaluating motor performance. All procedures adhere to established safety guidelines for TUS and TMS. This study will provide critical insights into state-dependent mechanisms of TUS-induced neuroplasticity, informing the development of optimized stimulation protocols for future therapeutic applications in neurological and psychiatric conditions.

Targeting the basal forebrain using TUS in healthy adults (1) and LBD patients (2)

Presented by Polytimi Frangou and Camille Lasbareilles

Abstract: Parkinson's disease (PD) is characterized by progressive motor and cognitive impairments. Approximately 70% of patients develop PD dementia (PDD) as the disease progresses, which presents with fluctuating cognition and attention, leading to severe impairments in quality of life and daily functioning. Cognitive functions, including memory and attention, depend critically on acetylcholine (ACh) signalling. One of the brain regions releasing ACh is the nucleus basalis of Meynert (nbM) within the basal forebrain and its degeneration is a hallmark pathological feature of PDD, contributing substantially to its cognitive symptoms. Current treatments for PDD rely on cholinesterase inhibitors, which enhance ACh signalling by preventing synaptic breakdown. However, these medications lack organ selectivity, causing side effects such as nausea, limiting their tolerability and dose and resulting in only modest improvements in brain ACh levels. An alternative approach is deep brain stimulation (DBS) of the nbM: preclinical evidence suggests that NBM-targeted DBS may enhance cholinergic release. However, despite its potential, DBS requires invasive neurosurgery, making it unsuitable for many patients. These limitations have driven the need for non-invasive neuromodulation approaches. Transcranial Ultrasound Stimulation (TUS) offers a promising alternative, enabling safe, non-invasive targeting of deep brain structures with high spatial specificity.

In this WIP, we will discuss two related projects:

1. The effect of NBM TUS on NBM-cortical functional connectivity, TMS- and MRS-measures of cholinergic signalling in healthy participants at 7 T (presented by Polytimi Frangou)

2. The effect of NBM TUS on NBM-cortical functional connectivity and MRS-measures of cholinergic signalling in patients with PDD at 3 T (presented by Camille Lasbareilles)

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