Frontiers in human neuroscience · 2026
Accelerated prefrontal intermittent theta-burst stimulation in Huntington's disease: a within-subject study of domain-specific behavioral and event-related potential changes.
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Delussi Marianna, Ladisa Emmanuella, Ammendola Elena, Paparella Giulia, Abbatantuono Chiara, Tancredi Giusy, Paparella Giulia, Brattico Elvira, de Tommaso Marina
Аннотация
BACKGROUND: Huntington's disease is a rare neurodegenerative movement disorder characterized by early disruption of frontostriatal systems, affecting motor, cognitive, and affective domains. Non-invasive brain stimulation targeting prefrontal networks may offer a means to modulate these distributed systems, although controlled evidence in Huntington's disease remains limited, particularly for accelerated stimulation protocols.
OBJECTIVE: To investigate whether accelerated intermittent theta-burst stimulation (iTBS) applied to the dorsolateral prefrontal cortex is associated with behavioral, motor and electrophysiological changes reflecting modulation of prefrontal network function in early-stage Huntington's disease.
METHODS: Ten patients with genetically confirmed Huntington's disease participated in a within-subject, fixed-order longitudinal study, which included a sham exposure phase followed by active stimulation. Assessments were conducted at baseline (T0), after sham stimulation (T1), after active accelerated iTBS (T2), and at 60-day follow-up (T3). Clinical scales for motor impairment, behavioral measures targeting executive, affective, and social-cognitive domains were combined with event-related potentials (ERPs) recorded during cognitive and emotional Stroop tasks. The fixed-order design was chosen to minimize potential carry-over effects associated with accelerated stimulation protocols.
RESULTS: No significant behavioral or electrophysiological changes were observed during the sham exposure phase. In contrast, active iTBS was associated with domain-specific behavioral changes, particularly in affective, executive, and social-cognitive domains, accompanied by changes in event-related potential activity, particularly within delayed N200-related responses during emotional interference. Effects were domain-specific and were not associated with normalization of electrophysiological latency profiles. Motor scales were not modified by either sham or real stimulation.
CONCLUSION: Accelerated prefrontal iTBS was associated with behavioral and electrophysiological changes following active stimulation of prefrontal network in Huntington's disease. These findings support the feasibility of targeting distributed non-motor circuits in HD and designs accounting for cumulative and time-dependent effects of stimulation in early-phase neuromodulation studies.
OBJECTIVE: To investigate whether accelerated intermittent theta-burst stimulation (iTBS) applied to the dorsolateral prefrontal cortex is associated with behavioral, motor and electrophysiological changes reflecting modulation of prefrontal network function in early-stage Huntington's disease.
METHODS: Ten patients with genetically confirmed Huntington's disease participated in a within-subject, fixed-order longitudinal study, which included a sham exposure phase followed by active stimulation. Assessments were conducted at baseline (T0), after sham stimulation (T1), after active accelerated iTBS (T2), and at 60-day follow-up (T3). Clinical scales for motor impairment, behavioral measures targeting executive, affective, and social-cognitive domains were combined with event-related potentials (ERPs) recorded during cognitive and emotional Stroop tasks. The fixed-order design was chosen to minimize potential carry-over effects associated with accelerated stimulation protocols.
RESULTS: No significant behavioral or electrophysiological changes were observed during the sham exposure phase. In contrast, active iTBS was associated with domain-specific behavioral changes, particularly in affective, executive, and social-cognitive domains, accompanied by changes in event-related potential activity, particularly within delayed N200-related responses during emotional interference. Effects were domain-specific and were not associated with normalization of electrophysiological latency profiles. Motor scales were not modified by either sham or real stimulation.
CONCLUSION: Accelerated prefrontal iTBS was associated with behavioral and electrophysiological changes following active stimulation of prefrontal network in Huntington's disease. These findings support the feasibility of targeting distributed non-motor circuits in HD and designs accounting for cumulative and time-dependent effects of stimulation in early-phase neuromodulation studies.