78 research outputs found

    Behavior and neuropsychiatric manifestations in Angelman syndrome

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    Angelman syndrome has been suggested as a disease model of neurogenetic developmental condition with a specific behavioral phenotype. It is due to lack of expression of the UBE3A gene, an imprinted gene located on chromosome 15q. Here we review the main features of this phenotype, characterized by happy demeanor with prominent smiling, poorly specific laughing and general exuberance, associated with hypermotor behavior, stereotypies, and reduced behavioral adaptive skills despite proactive social contact. All these phenotypic characteristics are currently difficult to quantify and have been subject to some differences in interpretation. For example, prevalence of autistic disorder is still debated. Many of these features may occur in other syndromic or nonsyndromic forms of severe intellectual disability, but their combination, with particularly prominent laughter and smiling may be specific of Angelman syndrome. Management of problematic behaviors is primarily based on behavioral approaches, though psychoactive medication (eg, neuroleptics or antidepressants) may be required

    The Lessons from Angelman Syndrome for Research and Management

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    BK Channels Control Cerebellar Purkinje and Golgi Cell Rhythmicity In Vivo

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    Calcium signaling plays a central role in normal CNS functioning and dysfunction. As cerebellar Purkinje cells express the major regulatory elements of calcium control and represent the sole integrative output of the cerebellar cortex, changes in neural activity- and calcium-mediated membrane properties of these cells are expected to provide important insights into both intrinsic and network physiology of the cerebellum. We studied the electrophysiological behavior of Purkinje cells in genetically engineered alert mice that do not express BK calcium-activated potassium channels and in wild-type mice with pharmacological BK inactivation. We confirmed BK expression in Purkinje cells and also demonstrated it in Golgi cells. We demonstrated that either genetic or pharmacological BK inactivation leads to ataxia and to the emergence of a beta oscillatory field potential in the cerebellar cortex. This oscillation is correlated with enhanced rhythmicity and synchronicity of both Purkinje and Golgi cells. We hypothesize that the temporal coding modification of the spike firing of both Purkinje and Golgi cells leads to the pharmacologically or genetically induced ataxia

    Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials

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    BACKGROUND: Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG) activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP) triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation. RESULTS: The frontal N30 component was accompanied by a significant phase-locking of beta/gamma oscillation (25-35 Hz) and to a lesser extent of 80 Hz oscillation. After the selection in each subject of the trials for which the power spectrum amplitude remained unchanged, we found pure phase-locking of beta/gamma oscillation (25-35 Hz) peaking about 30 ms after the stimulation. Transition across trials from uniform to normal phase distribution revealed temporal phase reorganization of ongoing 30 Hz EEG oscillations in relation to stimulation. In a proportion of trials, this phase-locking was accompanied by a spectral power increase peaking in the 30 Hz frequency band. This corresponds to the complex situation of 'phase-locking with enhancement' in which the distinction between the contribution of phasic neural event versus EEG phase resetting is hazardous. CONCLUSION: The identification of a pure phase-locking in a large proportion of the SEP trials reinforces the contribution of the oscillatory model for the physiological correlates of the frontal N30. This may imply that ongoing EEG rhythms, such as beta/gamma oscillation, are involved in somatosensory information processing.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

    Detection of Motor Cerebral Activity After Median Nerve Stimulation During General Anesthesia (STIM-MOTANA): Protocol for a Prospective Interventional Study

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    International audienceBackground Accidental awareness during general anesthesia (AAGA) is defined as an unexpected awareness of the patient during general anesthesia. This phenomenon occurs in 1%-2% of high-risk practice patients and can cause physical suffering and psychological after-effects, called posttraumatic stress disorder. In fact, no monitoring techniques are satisfactory enough to effectively prevent AAGA; therefore, new alternatives are needed. Because the first reflex for a patient during an AAGA is to move, but cannot do so because of the neuromuscular blockers, we believe that it is possible to design a brain-computer interface (BCI) based on the detection of movement intention to warn the anesthetist. To do this, we propose to describe and detect the changes in terms of motor cortex oscillations during general anesthesia with propofol, while a median nerve stimulation is performed. We believe that our results could enable the design of a BCI based on median nerve stimulation, which could prevent AAGA. Objective To our knowledge, no published studies have investigated the detection of electroencephalographic (EEG) patterns in relation to peripheral nerve stimulation over the sensorimotor cortex during general anesthesia. The main objective of this study is to describe the changes in terms of event-related desynchronization and event-related synchronization modulations, in the EEG signal over the motor cortex during general anesthesia with propofol while a median nerve stimulation is performed. Methods STIM-MOTANA is an interventional and prospective study conducted with patients scheduled for surgery under general anesthesia, involving EEG measurements and median nerve stimulation at two different times: (1) when the patient is awake before surgery (2) and under general anesthesia. A total of 30 patients will receive surgery under complete intravenous anesthesia with a target-controlled infusion pump of propofol. Results The changes in event-related desynchronization and event-related synchronization during median nerve stimulation according to the various propofol concentrations for 30 patients will be analyzed. In addition, we will apply 4 different offline machine learning algorithms to detect the median nerve stimulation at the cerebral level. Recruitment began in December 2022. Data collection is expected to conclude in June 2024. Conclusions STIM-MOTANA will be the first protocol to investigate median nerve stimulation cerebral motor effect during general anesthesia for the detection of intraoperative awareness. Based on strong practical and theoretical scientific reasoning from our previous studies, our innovative median nerve stimulation–based BCI would provide a way to detect intraoperative awareness during general anesthesia. Trial Registration Clinicaltrials.gov NCT05272202; https://clinicaltrials.gov/ct2/show/NCT05272202 International Registered Report Identifier (IRRID) PRR1-10.2196/4387

    Sensory Stimulation-Dependent Plasticity in the Cerebellar Cortex of Alert Mice

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    In vitro studies have supported the occurrence of cerebellar long-term depression (LTD), an interaction between the parallel fibers and Purkinje cells (PCs) that requires the combined activation of the parallel and climbing fibers. To demonstrate the existence of LTD in alert animals, we investigated the plasticity of local field potentials (LFPs) evoked by electrical stimulation of the whisker pad. The recorded LFP showed two major negative waves corresponding to trigeminal (broken into the N2 and N3 components) and cortical responses. PC unitary extracellular recording showed that N2 and N3 occurred concurrently with PC evoked simple spikes, followed by an evoked complex spike. Polarity inversion of the N3 component at the PC level and N3 amplitude reduction after electrical stimulation of the parallel fiber volley applied on the surface of the cerebellum 2 ms earlier strongly suggest that N3 was related to the parallel fiber–PC synapse activity. LFP measurements elicited by single whisker pad stimulus were performed before and after trains of electrical stimuli given at a frequency of 8 Hz for 10 min. We demonstrated that during this later situation, the stimulation of the PC by parallel and climbing fibers was reinforced. After 8-Hz stimulation, we observed long-term modifications (lasting at least 30 min) characterized by a specific decrease of the N3 amplitude accompanied by an increase of the N2 and N3 latency peaks. These plastic modifications indicated the existence of cerebellar LTD in alert animals involving both timing and synaptic modulations. These results corroborate the idea that LTD may underlie basic physiological functions related to calcium-dependent synaptic plasticity in the cerebellum