The cerebellum: a transdiagnostic personalised target for neuromodulation in psychiatry

Descrizione del progetto

Sfruttare il cervelletto per trattare i sintomi psichiatrici resistenti

Oltre a coordinare i movimenti, il cervelletto svolge anche un ruolo attivo nel plasmare il modo in cui pensiamo e sentiamo: pur occupando solo il 10 % del volume del cervello, vi si trova più della metà dei nostri neuroni. Molti di questi sono collegati alle aree responsabili del pensiero di ordine superiore, il che rende il cervelletto un obiettivo primario per la stimolazione cerebrale non invasiva. Il progetto CLOVIS, finanziato dal CER, si propone di sfruttare questa connessione per trattare i sintomi della schizofrenia o del disturbo bipolare, in particolare quelli che non rispondono in maniera efficace ai farmaci convenzionali. Il progetto utilizzerà modelli di risonanza magnetica e registrazioni cerebrali dirette individuando esattamente dove e come applicare la stimolazione per ottenere i migliori risultati, con l’obiettivo di passare dalle teorie di laboratorio alla sperimentazione clinica e di dimostrare che la stimolazione cerebrale personalizzata può effettivamente migliorare la vita quotidiana delle persone affette da queste patologie.

Obiettivo

Have you ever had that moment where you reach for something, convinced it is heavy, but it is actually light? Your arm jolts upward, correcting itself before you realise the difference. This split second adjustment is thanks to your cerebellum, the part of your brain responsible for fine-tuning movements by integrating sensory feedback. While the cerebellum is traditionally associated with motor control, it plays a similar role in cognitive functions. Despite occupying 10% of the brain’s volume, the cerebellum houses more than 50% of its neurons, many of which are integral to higher cognitive processes. Its extensive connections with brain regions responsible for complex thought and emotion make it a promising target for non-invasive brain stimulation (NIBS) especially in addressing the resistant cognitive and negative symptoms observed in psychiatric disorders such as schizophrenia, bipolar disorder, and autism. However, a significant challenge persists: clinical research on NIBS often relies on a trial-and-error approach, while fundamental research has yet to fully translate electrophysiological findings into circuit-level applications that can guide clinical interventions. To bridge this gap, I will develop normative models from large-scale MRI cohorts to identify patients who are most likely to benefit from cerebellar stimulation and then derive a personalised cerebellar target. Concurrently, animal studies using ultra-high field MRI will be conducted to determine optimal cerebellar stimulation parameters. With intracranial recordings, I will explore the neuroplastic changes induced by NIBS in humans. The project will culminate in a proof-of-concept clinical trial aiming at improving cognitive and negative symptoms across schizophrenia, bipolar disorder and autism with cerebellar NIBS. This multidisciplinary project has the potential to revolutionize the treatment of resistant psychiatric symptoms and catalyse advancements in the understanding of NIBS.