Publications by authors named "Catherine Vanasse"

3 Publications

  • Page 1 of 1

Reversing frontal disinhibition rescues behavioural deficits in models of CACNA1A-associated neurodevelopment disorders.

Mol Psychiatry 2021 Jun 14. Epub 2021 Jun 14.

CHU Ste-Justine Research Center, Montreal, QC, Canada.

CACNA1A deletions cause epilepsy, ataxia, and a range of neurocognitive deficits, including inattention, impulsivity, intellectual deficiency and autism. To investigate the underlying mechanisms, we generated mice carrying a targeted Cacna1a deletion restricted to parvalbumin-expressing (PV) neurons (PV;Cacna1a) or to cortical pyramidal cells (PC) (Emx1;Cacna1a). GABA release from PV-expressing GABAergic interneurons (PV-INs) is reduced in PV;Cacna1a mutants, resulting in impulsivity, cognitive rigidity and inattention. By contrast, the deletion of Cacna1a in PCs does not impact cortical excitability or behaviour in Emx1;Cacna1a mutants. A targeted Cacna1a deletion in the orbitofrontal cortex (OFC) results in reversal learning deficits while a medial prefrontal cortex (mPFC) deletion impairs selective attention. These deficits can be rescued by the selective chemogenetic activation of cortical PV-INs in the OFC or mPFC of PV;Cacna1a mutants. Thus, Cacna1a haploinsufficiency disrupts perisomatic inhibition in frontal cortical circuits, leading to a range of potentially reversible neurocognitive deficits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-021-01175-1DOI Listing
June 2021

Potential brain language reorganization in a boy with refractory epilepsy; an fNIRS-EEG and fMRI comparison.

Epilepsy Behav Case Rep 2016 9;5:34-7. Epub 2016 Feb 9.

CHU Sainte-Justine Research Center, Montreal, Quebec, Canada; Psychology Department, Centre de Recherche de Neuropsychologie et Cognition (CERNEC), Université de Montréal, Quebec, Canada.

As part of a presurgical investigation for a resection of a tumor located in the left temporal brain region, we evaluated pre- and postsurgical language lateralization in a right-handed boy with refractory epilepsy. In this study, we compared functional near infrared spectroscopy (fNIRS) results obtained while the participant performed expressive and receptive language tasks with those obtained using functional magnetic resonance imaging (fMRI). This case study illustrates the potential for NIRS to contribute favorably to the localization of language functions in children with epilepsy and cognitive or behavioral problems and its potential advantages over fMRI in presurgical assessment. Moreover, it suggests that fNIRS is sensitive in localizing an atypical language network or potential brain reorganization related to epilepsy in young patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebcr.2016.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782003PMC
March 2016

CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms.

Eur J Hum Genet 2015 Nov 4;23(11):1505-12. Epub 2015 Mar 4.

Department of Pediatrics, Neurology Service, CHU Ste-Justine, U. de Montréal, Montreal, Quebec, Canada.

CACNA1A loss-of-function mutations classically present as episodic ataxia type 2 (EA2), with brief episodes of ataxia and nystagmus, or with progressive spinocerebellar ataxia (SCA6). A minority of patients carrying CACNA1A mutations develops epilepsy. Non-motor symptoms associated with these mutations are often overlooked. In this study, we report 16 affected individuals from four unrelated families presenting with a spectrum of cognitive impairment including intellectual deficiency, executive dysfunction, ADHD and/or autism, as well as childhood-onset epileptic encephalopathy with refractory absence epilepsy, febrile seizures, downbeat nystagmus and episodic ataxia. Sequencing revealed one CACNA1A gene deletion, two deleterious CACNA1A point mutations including one known stop-gain and one new frameshift variant and a new splice-site variant. This report illustrates the phenotypic heterogeneity of CACNA1A loss-of-function mutations and stresses the cognitive and epileptic manifestations caused by the loss of CaV2.1 channels function, presumably affecting cerebellar, cortical and limbic networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ejhg.2015.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613477PMC
November 2015
-->