E017 Examining cognitive and motor network dysfunction in premanifest Huntington’s disease using neuronavigated transcranial magnetic stimulation

<h3>Background</h3> Early Huntington’s Disease (HD) pathology features white matter deficits in the corpus callosum,¹ indicating that measures of interhemispheric connectivity could serve as valuable premanifest HD (pHD) biomarkers.² Dual-coil paired-pulse transcranial magnetic stimulation (ppTMS) can be used to examine causal interactions between motor/cognitive regions and the contralateral motor cortex.³ Evaluating callosal projection integrity with TMS offers a cost-effective, non-invasive method to detect network dysfunction prior to clinical HD manifestation. <h3>Aims</h3> To evaluate potential ppTMS-based biomarkers for the identification of pHD. <h3>Methods</h3> Structural 3T MRI scans are collected from people with pHD and control participants. EMG from the dominant abductor pollicis brevis (APB) muscle records motor evoked potentials (MEPs) elicited by TMS. A threshold-tracking algorithm determines the stimulation intensity ‘threshold’ required to evoke MEPs of at least 200µV peak-to-peak amplitude in 50% of trials in the dominant motor cortex (M1).⁴ This is repeated with conditioning stimuli targeting premotor regions, M1, or dorsolateral prefrontal regions in the non-dominant hemisphere, 10ms or 40ms before test stimuli in the dominant M1. TMS coils are positioned and tracked using the Brainsight neuronavigation system. Sign rank testing identifies regions which exert significant inhibition/facilitation on dominant M 1 in controls; rank sum testing identifies significant differences in inhibition/facilitation between cohorts. <h3>Results</h3> Significant inhibition (p&lt;0.05) of M1 by contralateral M1 and premotor (6a and 6d) regions has been observed in controls (n=16). Measures have been collected in 3 individuals with pHD (n=3) to date. <h3>Conclusion</h3> Following further recruitment, we will report pilot findings comparing interhemispheric connectivity between pHD (n=6) and controls (n=16). <h3>References</h3> Casella, <i>et al. Neuroimage Clin</i> 2021. Calvert, <i>et al. Clinical Neurophysiology</i> 2020. Moliadze, <i>et al. J Physiology</i> 2005. McMackin, <i>et al. Clin Neurophysiol Practice</i> 2024.