Theta burst stimulation modulates cerebellar-cortical connectivity in patients with progressive supranuclear palsy.
BACKGROUND
Progressive Supranuclear Palsy (PSP) is an atypical degenerative Parkinsonism characterized by postural instability, supranuclear gaze palsy and frontal deficits. Recent imaging studies revealed that the volume of cerebellar peduncles and midbrain were reduced in PSP. Transcranial magnetic stimulation (TMS) studies demonstrated a cerebellar involvement in PSP showing an impairment of functional connectivity between the cerebellar hemisphere (Cb) and the contralateral primary motor cortex (M1) (cerebellar brain inhibition-CBI).


OBJECTIVE
To investigate the plasticity of the cerebello-thalamo-cortical circuits in ten PSP patients after two-week course of cerebellar intermittent theta burst stimulation (iTBS), a form of repetitive TMS.


METHODS
Before and after the iTBS sessions we measured functional connectivity between Cb and contralateral M1 (CBI), short intracortical inhibition (SICI) and intracortical facilitation (ICF) and short latency afferent inhibition (SLAI) in contralateral M1. We also performed resting state functional magnetic resonance (rs-fMRI) and we administered clinical rating scale (PSP-RS).


RESULTS
At baseline PSP patients had decreased efficiency of CBI, SICI and SLAI in comparison to PD patients and healthy subjects. Cerebellar iTBS increased the deficient functional cerebellar-motor connectivity as assessed by CBI. No effect was seen for SICI/ICF and SLAI circuits. Following iTBS there was an increased signal in the head of the caudate nucleus bilaterally as shown by rs-fMRI. Moreover, PSP-RS showed an improvement of dysarthria in all patients.


CONCLUSIONS
iTBS enhanced functional connectivity between the cerebellar hemisphere, the caudate nucleus and the cortex, that was paralleled by some clinical improvement. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.
UOC Neurologia, Ospedale S. Eugenio, P.le dell'Umanesimo 10, 00144 Rome, Italy.
Livia
L
Brusa
Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy.
Viviana
V
Ponzo
Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy.
Chiara
C
Mastropasqua
Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy.
Silvia
S
Picazio
Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy.
Sonia
S
Bonnì
Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy.
Francesco
F
Di Lorenzo
UOC Neurologia, Ospedale S. Eugenio, P.le dell'Umanesimo 10, 00144 Rome, Italy.
Cesare
C
Iani
Department of Neuroscience, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy.
Alessandro
A
Stefani
Department of Neuroscience, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy.
Paolo
P
Stanzione
Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy; Department of Neuroscience, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy.
Carlo
C
Caltagirone
Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy.
Marco
M
Bozzali
Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, Italy; Department of Neuroscience, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy. Electronic address: g.koch@hsantalucia.it.
Giacomo
G
Koch
D000368:Aged; D002531:Cerebellum / Q000503:physiopathology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology; D013494:Supranuclear Palsy, Progressive / Q000628:therapy*; D013826:Theta Rhythm / Q000502:physiology; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
Cerebellar brain inhibition; Progressive Supranuclear Palsy; Theta burst stimulation