Related Experiment Video
Updated: Mar 28, 2026
Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism
Published on: October 17, 2025
Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the
Sandrine Passemard1, Alain Verloes2, Thierry Billette de Villemeur3
1Inserm, U1141, Hôpital Robert Debré, Paris, France; Université Paris Diderot - Sorbonne Paris Cité, Paris, France; Département de Génétique, Hôpital Robert Debré, AP-HP, Paris, France; Service de Neuropédiatrie, Hôpital Robert Debré, AP-HP, Paris, France.
Abstract:
Autosomal recessive primary microcephaly results from abnormal brain development linked to proliferation defects in neural progenitors. The most frequent form, caused by ASPM mutations, is usually defined by a reduced brain volume and is associated with intellectual disability. Although many ASPM cases have now been reported, structural brain abnormalities and their link with cognitive disabilities have rarely been investigated. In this study, we used high resolution T1-weighted magnetic resonance imaging in seven patients with ASPM mutations and 39 healthy age-matched controls to quantify regional volumes, thickness, surface area, gyrification index and white matter volumes of 30 cortical regions. We observed a consistent reduction of 50% or more in the volume and surface area of all cortical regions except for the hippocampus and surrounding medial temporal structures, which were significantly less reduced. Neuropsychologic assessment indicated significant impairments of cognitive abilities. However, these impairments were associated with normal mnesic abilities, in keeping with the relative preservation of the hippocampus and medial temporal structures. These results show that, contrary to current opinion, the cortical volume and surface area of patients with ASPM mutations is reduced depending on a regionally specific fashion and their cognitive profile reflects this heterogeneity. The precise characterization of the cortical map and cognitive abilities of patients with ASPM mutations should allow developing more focused reeducative interventions well-suited to their real abilities.
Insights
Autosomal recessive primary microcephaly (ARPM) linked to ASPM mutations causes significant brain volume reduction. Cognitive impairments in ARPM patients are regionally specific, reflecting heterogeneous brain development.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Autosomal recessive primary microcephaly (ARPM) is a neurodevelopmental disorder characterized by reduced brain size.
- The most common form of ARPM is caused by mutations in the ASPM gene, leading to intellectual disability.
- Structural brain abnormalities and their correlation with cognitive deficits in ARPM patients remain under-investigated.
Purpose of the Study:
- To investigate detailed structural brain abnormalities in patients with ASPM mutations using high-resolution MRI.
- To correlate neuroimaging findings with cognitive and mnesic abilities in affected individuals.
- To challenge the notion of uniform cortical reduction in ASPM-related microcephaly.
Main Methods:
- High-resolution T1-weighted MRI scans were acquired from seven patients with ASPM mutations and 39 healthy controls.
- Quantitative analysis of regional cortical volumes, thickness, surface area, gyrification index, and white matter volumes across 30 cortical regions.
- Neuropsychological assessments were performed to evaluate cognitive and mnesic functions.
Main Results:
- A significant reduction (≥50%) in cortical volume and surface area was observed in most cortical regions.
- The hippocampus and medial temporal structures showed relative preservation compared to other cortical regions.
- Patients exhibited significant cognitive impairments but preserved mnesic abilities, correlating with hippocampal preservation.
Conclusions:
- ASPM mutations lead to regionally specific reductions in cortical volume and surface area, not uniform microcephaly.
- The cognitive profile of ASPM patients reflects this regional brain heterogeneity, with preserved memory functions.
- Detailed characterization of brain structure and cognitive abilities can inform targeted therapeutic interventions for ASPM patients.
More Related Videos
10:29Inducing Cre-lox Recombination in Mouse Cerebral Cortex Through In Utero Electroporation
Published on: November 17, 2017
07:43Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Related Concept Videos
01:39Mutations
01:35Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...