RESUMO
Background: Fragile X syndrome (FXS) is the leading cause of genetic intellectual disability. Among the neurobehavioral dysfunctions in FXS individuals, language development and literacy are compromised. Recent evidence hypothesized that the disruption of excitatory glutamatergic and GABAergic inhibitory neurotransmission balance might be responsible for impairment in cognitive function. In this study, we evaluated for the first time, the safety, tolerability, and efficacy of anodal prefrontal transcranial direct current stimulation (tDCS) combined with standard speech therapy to enhance language function in FXS patients. Methods: In total, 16 adult FXS patients were enrolled. Participants underwent 45 min of anodic tDCS combined with speech therapy for 5 weeks (3 times per week). Language function was evaluated using the Test for Reception of Grammar-Version 2 (TROG-2) and subtests of the Italian Language Examination (Esame del Linguaggio - II, EDL-II). Right and left dorsolateral prefrontal cortex transcranial magnetic stimulation and concurrent electroencephalography (TMS-EEG) recordings were collected at baseline and after the treatment to evaluate cortical reactivity and connectivity changes. Results: After 5 weeks of combined therapy, we observed a significant improvement in the writing (7.5%), reading (20.3%), repetition (13.3%), and TROG-2 (10.2%) tests. Parallelly with clinical change, TMS-EEG results showed a significant difference in TMS-evoked potential amplitude over the left frontal cortex after treatment (-0.73 ± 0.87 µV) compared to baseline (0.18 ± 0.84 µV). Conclusion: Our study provides novel evidence that left anodal prefrontal tDCS combined with standard speech therapy could be effective in enhancing language function in FXS patients, mainly by inducing a rebalance of the dysfunctional prefrontal cortical excitability.
RESUMO
BACKGROUND: Since birth, during the exploration of the environment to interact with objects, we exploit both the motor and sensory components of the upper limb (UL). This ability to integrate sensory and motor information is often compromised following a stroke. However, to date, rehabilitation protocols are focused primarily on recovery of motor function through physical therapies. Therefore, we have planned a clinical trial to investigate the effect on functionality of UL after a sensorimotor transcranial stimulation (real vs sham) in add-on to robot-assisted therapy in the stroke population. METHODS: A randomised double-blind controlled trial design involving 32 patients with a single chronic stroke (onset > 180 days) was planned. Each patient will undergo 15 consecutive sessions (5 days for 3 weeks) of paired associative stimulation (PAS) coupled with UL robot-assisted therapy. PAS stimulation will be administered using a bifocal transcranial magnetic stimulator (TMS) on the posterior-parietal cortex and the primary motor area (real or sham) of the lesioned hemisphere. Clinical, kinematics and neurophysiological changes will be evaluated at the end of protocol and at 1-month follow-up and compared with baseline. The Fugl-Meyer assessment scale will be the primary outcome. Secondly, kinematic variables will be recorded during the box-and-block test and reaching tasks using video analysis and inertial sensors. Single pulse TMS and electroencephalography will be used to investigate the changes in local cortical reactivity and in the interconnected areas. DISCUSSION: The presented trial shall evaluate with a multimodal approach the effects of sensorimotor network stimulation applied before a robot-assisted therapy training on functional recovery of the upper extremity after stroke. The combination of neuromodulation and robot-assisted therapy can promote an increase of cortical plasticity of sensorimotor areas followed by a clinical benefit in the motor function of the upper limb. TRIAL REGISTRATION: ClinicalTrials.gov NCT05478434. Registered on 28 Jul 2022.