Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity

Paul, Lynn K.; Brown, Warren S.; Adolphs, Ralph; Tyszka, J. Michael; Richards, Linda J.; Mukherjee, Pratik; Sherr, Elliott H.

doi:10.1038/nrn2107

Cited by 736 publications

(776 citation statements)

References 146 publications

(159 reference statements)

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“…ACC is among the characteristic features of ARX-associated lissencephaly. 26,27 The frequent association of ACC with vLIS-ND patients in our series suggests considering this feature as a supplementary criteria to differentiate cLIS from vLIS. It is important to note, however, that ACC may also be found in other types of lissencephalies.…”

Section: Resultsmentioning

confidence: 99%

Midbrain–hindbrain involvement in lissencephalies

Jissendi-Tchofo¹,

Kara²,

Barkovich³

2009

Neurology

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Objectives:To determine the involvement of the midbrain and hindbrain (MHB) in the groups of classic (cLIS), variant (vLIS), and cobblestone complex (CBSC) lissencephalies and to determine whether a correlation exists between the cerebral malformation and the MHB abnormalities.Methods: MRI scans of 111 patients (aged 1 day to 32 years; mean 5 years 4 months) were retrospectively reviewed. After reviewing the brain involvement on MRI, the cases were reclassified according to known mutation (LIS1, DCX, ARX, VLDLR, RELN, MEB, WWS) or mutation phenotype (LIS1-P, DCX-P, RELN-P, ARX-P, VLDLR-P) determined on the basis of characteristic MRI features. Abnormalities in the MHB were then recorded. For each structure, a score was assigned, ranging from 0 (normal) to 3 (severely abnormal). The differences between defined groups and the correlation between the extent of brain agyria/pachygyria and MHB involvement were assessed using Kruskal-Wallis and 2 McNemar tests. Results:There was a significant difference in MHB appearance among the three major groups of cLIS, vLIS, and CBSC. The overall score showed a severity gradient of MHB involvement: cLIS (0 or 1), vLIS (7), and CBSC (11 or 12). The extent of cerebral lissencephaly was significantly correlated with the severity of MHB abnormalities (p ϭ 0.0029). Conclusion: GLOSSARYA ϭ autosomal; ACC ϭ agenesis of corpus callosum; AD ϭ autosomal dominant; AP ϭ anteroposterior; AR ϭ autosomal recessive; CBL ϭ cerebellar; CBSC ϭ cobblestone complex; cLIS ϭ classic lissencephaly; CMD ϭ congenital muscular dystrophy; CSZ ϭ cell-sparse zone; DV ϭ dorsal-ventral; FCMD ϭ Fukuyama congenital muscular dystrophy; IVH ϭ inferior vermis hypoplasia; LV ϭ lateral ventricle; m ϭ medulla; M ϭ midbrain; MDS ϭ Miller-Dieker syndrome; MEB ϭ muscle-eyebrain; MHB ϭ midbrain and hindbrain; MR ϭ magnetic resonance; ND ϭ not determined; P ϭ pons; RC ϭ rostrocaudal; SCBH ϭ subcortical band heterotopia; SELH ϭ subependymal linear heterotopia; V ϭ vermis; vLIS ϭ variant lissencephaly; WI ϭ weighted image; WWS ϭ Walker-Warburg syndrome; XLD ϭ X-linked dominant; XLR ϭ X-linked recessive.The term lissencephaly (smooth outer brain surface) refers to a paucity of gyral and sulcal development. 1 It encompasses a spectrum of gyral malformations ranging from complete agyria to regional pachygyria and includes subcortical band heterotopia. Lissencephaly has been traditionally classified in two distinct groups: classic (cLIS, formerly called lissencephaly type 1) and cobblestone complex (CBSC, formerly called lissencephaly type 2) based on both brain imaging and pathology. To date, five genes have been identified as causing or contributing to human cLIS: LIS1, 14-3-3 in Miller-Dieker syndrome (MDS), DCX, RELN, and ARX. [1][2][3][4][5][6] A new classification has recently been proposed defining four groups of cLIS differing from each other by genetics and neuropathologic features of the cerebral cortex, cerebellum, and brainstem. 3 1)

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Section: Resultsmentioning

confidence: 99%

Midbrain–hindbrain involvement in lissencephalies

Jissendi-Tchofo¹,

Kara²,

Barkovich³

2009

Neurology

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“…Patients with agenesis of the corpus callosum often have impoverished and superficial relationships, suffer from social isolation, and have interpersonal conflicts both at home and at work due to misinterpretation of social cues (Paul et al 2007). Kaufman et al (2008) found that the VENs were reduced by 50% in a subject with partial agenesis of the corpus callosum and 90% in a subject with complete agenesis, compared to adult controls.…”

Section: Introductionmentioning

confidence: 99%

The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

et al. 2010

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The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decisionmaking, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology.

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“…The effectiveness of ECT in BTBR mice is particularly remarkable considering that these animals have profound and irreversible deficiency in interhemispheric connectivity due to the missing corpus callosum and underdeveloped hippocampal commissure [41,42], which is congruent with compromised long-range connectivity in autism [43][44][45]. However, it should be noted that the lack of corpus callosum alone cannot explain the presence of autism-like behavior; indeed, postnatal mechanical lesion to the corpus callosum in LP/J mice (which are genetically close to BTBR mice but show no autism-like behavioral abnormalities) failed to produce autism-like impairments [46].…”

Section: Discussionmentioning

confidence: 99%

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy

et al. 2015

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Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino--(methylsulfonyl)butanamide hydrochloride abolished ECTinduced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.

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Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity

Cited by 736 publications

References 146 publications

Midbrain–hindbrain involvement in lissencephalies

Midbrain–hindbrain involvement in lissencephalies

The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy

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