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1.
Exp Neurol ; 370: 114581, 2023 12.
Article in English | MEDLINE | ID: mdl-37884190

ABSTRACT

Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatment.


Subject(s)
Epilepsies, Myoclonic , NAV1.1 Voltage-Gated Sodium Channel , Animals , Mice , Humans , NAV1.1 Voltage-Gated Sodium Channel/genetics , Epilepsies, Myoclonic/genetics , Epilepsies, Myoclonic/therapy , Seizures/therapy , Seizures/genetics , Transcranial Magnetic Stimulation , Disease Models, Animal , Magnetic Phenomena
2.
Neurotox Res ; 18(3-4): 416-27, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20405351

ABSTRACT

In order to adjust the behavioral performance in a changing environment, subjects have to monitor their evolving actions and to know whether their responses were correct or incorrect. This requires self-awareness, cognitive flexibility, working memory (WM), and decision making that frequently are impaired in psychosis. What is the neural substrate of these processes and where are these substrates located? Dysfunction of prefrontal, parietal, temporal cortices, and associated subcortical structures are known to be involved in some of these symptoms. The prefrontal-subcortical circuits have been the main focus of study while other cortical areas such as the premotor cortex have received less attention. The main focus of this review is about the evidence that the ventral premotor cortex processes both recent sensory information and that from long-term memory to decide and evaluate the behavior of previous decisions. This process may serve for learning and thus adapting future behavior to environmental demands. Therefore, dysfunction of this cortical area could be related to some cognitive neuropsychiatric disorders.


Subject(s)
Cerebral Cortex/physiology , Decision Making/physiology , Executive Function/physiology , Learning/physiology , Psychomotor Performance/physiology , Animals , Humans , Nerve Net/physiology , Prefrontal Cortex/physiology
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