Bernardo, Pia (2021) ALTERED BRAIN NETWORKS IN RETT SYNDROME: NEUROPHYSIOLOGICAL SIGNATURES. [Tesi di dottorato]
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| Item Type: | Tesi di dottorato | ||||
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| Resource language: | English | ||||
| Title: | ALTERED BRAIN NETWORKS IN RETT SYNDROME: NEUROPHYSIOLOGICAL SIGNATURES | ||||
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| Date: | 5 April 2021 | ||||
| Number of Pages: | 44 | ||||
| Institution: | Università degli Studi di Napoli Federico II | ||||
| Department: | Scienze Mediche Traslazionali | ||||
| Dottorato: | Medicina clinica e sperimentale | ||||
| Ciclo di dottorato: | 33 | ||||
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| Date: | 5 April 2021 | ||||
| Number of Pages: | 44 | ||||
| Keywords: | rett syndrome, synaptic plasticity, motor deficit, neurophysiological marker | ||||
| Settori scientifico-disciplinari del MIUR: | Area 06 - Scienze mediche > MED/26 - Neurologia Area 06 - Scienze mediche > MED/38 - Pediatria generale e specialistica Area 06 - Scienze mediche > MED/39 - Neuropsichiatria infantile |
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| Date Deposited: | 20 Apr 2021 07:37 | ||||
| Last Modified: | 07 Jun 2023 10:20 | ||||
| URI: | http://www.fedoa.unina.it/id/eprint/14157 |
Collection description
Objective: Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder due to pathogenic mutations in the MECP2 gene. Motor impairment constitutes the core diagnostic feature of RTT. Preclinical studies have consistently demonstrated alteration of excitation/inhibition (E/I) balance and aberrant synaptic plasticity at the cortical level. We aimed to understand neurobiological mechanisms underlying motor deficit by assessing in vivo synaptic plasticity and E/I balance in the primary motor cortex (M1). Methods: In the first work, we included 14 patients with typical RTT, 9 epilepsy control patients, and 11 healthy controls, we applied paired-pulse transcranial magnetic stimulation (TMS) protocols to evaluate the excitation index, a biomarker reflecting the contribution of inhibitory and facilitatory circuits in M1. Intermittent TMS-theta burst stimulation was used to probe long-term potentiation (LTP)-like plasticity in M1. Motor impairment, assessed by ad hoc clinical scales, was correlated with neurophysiological metrics. In the second study, we have studied 10 girls with RTT, using magnetoencephalography (MEG), based our analyses on source-reconstructed MEG data acquired during resting state. Results: RTT patients displayed a significant increase of the excitation index (p = 0.003), as demonstrated by the reduction of short-interval intracortical inhibition and increase of intracortical facilitation, suggesting a shift toward cortical excitation likely due to GABAergic dysfunction. Impairment of inhibitory circuits was also confirmed by the reduction of long-interval intracortical inhibition (p = 0.002). LTP-like plasticity in M1 was abolished (p = 0.008) and scaled with motor disability (all p = 0.003). In addition, the MEG data suggested an alteration of brain connectivity. Interpretation: To the best of our knowledge, this is the first study showing abnormalities of the E/I balance and synaptic plasticity in humans with RTT. These alterations were associated with a greater degree of functional motor disabilities, suggesting a pathophysiologic role of these functional changes. TMS is a method that can be used to assess cortical motor function in RTT patients. Our findings support the introduction of TMS measures in clinical and research settings to monitor the progression of motor deficit and response to treatment.
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