The functional characterization of callosal connections

Innocenti, Giorgio M.; Schmidt, Kerstin; Milleret, Chantal; Fabri, Mara; Knyazeva, Maria G.; Battaglia-Mayer, Alexandra; Aboitiz, Francisco; Ptito, Maurice; Caleo, Matteo; Marzi, Carlo Alberto; Baraković, Muhamed; Leporé, Franco; Caminiti, Roberto

doi:10.1016/j.pneurobio.2021.102186

Cited by 41 publications

(37 citation statements)

References 310 publications

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“…The corpus callosum is a white matter ber that connects the cerebral cortex and is linked to higher brain functions. [21] A 53-year-old woman presenting with callosal disconnection syndrome (CDS) as a result of a stroke presents with ideomotor apraxia, and tactile anomia with the left hand, cross-replication of hand postures, cross-localization of the ngers, and constructional impairment with the right hand. [22] Epilepsy has been reported in up to two-thirds of people with corpus callosum hypoplasia or partial hypoplasia.…”

Section: Discussionmentioning

confidence: 99%

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Retrospective analysis of 21 cases of Marchiafava-Bignami disease in alcoholic in Southwest China

Wang

et al. 2023

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Marchiafava-Bignami disease (MBD) is a rare disease with only a few reports worldwide. To describe clinical features and identify difficulties in the treatment of alcohol-related MBD, we performed a retrospective study of 21 MBD inpatients at a hospital in Southwest China. The interquartile range (IQR) for age was 53-66, with a mean age of 59 years. The IQR for drinking duration was 30-40, with a mean drinking length of 35.5 years. Cognitive impairment and unconsciousness were the most common symptoms (n=13, [61.9%]). Consciousness disorders, delirium, irritability, and ataxia are more prevalent in type A MBD patients; seizures, cognitive impairment, and limb weakness are more common in type B MBD patients. Routine blood and biochemical tests in alcoholic MBD patients may demonstrate orthocytic hypochromic anaemia and impaired liver function. Patients' uric acid (UA), potassium, and sodium levels may be normal. Eight patients received thiamine, while one received steroids. The average stay was 15 days. At the time of discharge, there had been no deaths. One patient died six months after being discharged, while another died two years afterwards. Indeed, MBD is a rare alcohol-related disorder with a variety of clinical symptoms. With thiamine treatment, prognosis is positive.

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Section: Discussionmentioning

confidence: 99%

“…[25] The corpus callosum projection neurons are pyramidal cells that use mainly glutamate or aspartate as neurotransmitters. [21] Vascular and non-vascular factors can both result in corpus callosum lesions. Tumors, trauma, demyelination, abscesses, ischemic and hypoxic injuries, etc.…”

Section: Discussionmentioning

confidence: 99%

Retrospective analysis of 21 cases of Marchiafava-Bignami disease in alcoholic in Southwest China

Wang

et al. 2023

Preprint

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“…Thus, callosal axons preferentially drive post-synaptic targets, precisely because they are coupled to specific inputs. This organization of inter-hemispheric fibers in the structure may endow the cortical network with a degree of condition-specific flexibility [ 83 ]. Accordingly, the spatial loci of inter-group differences in the corpus callosum in each of the conditions assume significance.…”

Section: Discussionmentioning

confidence: 99%

Inefficient white matter activity in Schizophrenia evoked during intra and inter-hemispheric communication

et al. 2022

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Intensive cognitive tasks induce inefficient regional and network responses in schizophrenia (SCZ). fMRI-based studies have naturally focused on gray matter, but appropriately titrated visuo-motor integration tasks reliably activate inter- and intra-hemispheric white matter pathways. Such tasks can assess network inefficiency without demanding intensive cognitive effort. Here, we provide the first application of this framework to the study of white matter functional responses in SCZ. Event-related fMRI data were acquired from 28 patients (nine females, mean age 43.3, ±11.7) and 28 age- and gender-comparable controls (nine females, mean age 42.1 ± 10.1), using the Poffenberger paradigm, a rapid visual detection task used to induce intra- (ipsi-lateral visual and motor cortex) or inter-hemispheric (contra-lateral visual and motor cortex) transfer. fMRI data were pre- and post-processed to reliably isolate activations in white matter, using probabilistic tractography-based white matter tracts. For intra- and inter-hemispheric transfer conditions, SCZ evinced hyper-activations in longitudinal and transverse white matter tracts, with hyper-activation in sub-regions of the corpus callosum primarily observed during inter-hemispheric transfer. Evidence for the functional inefficiency of white matter was observed in conjunction with small (~50 ms) but significant increases in response times. Functional inefficiencies in SCZ are (1) observable in white matter, with the degree of inefficiency contextually related to task-conditions, and (2) are evoked by simple detection tasks without intense cognitive processing. These cumulative results while expanding our understanding of this dys-connection syndrome, also extend the search of biomarkers beyond the traditional realm of fMRI studies of gray matter.

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“…Interhemispheric connectivity represents a predominant type of long-range connection mediated by callosal projection neurons (CPN) whose axons bundle to form the corpus callosum (CC). They mediate hemispheric integration of lateralized cues and facilitate the execution of complex cortical functions that require bilateral processing, including cognition, social communication, visual and sensory-motor processing, and associative integration [5][6][7][8], all of which are commonly disrupted in NDD. Although NDD encompass a heterogenous group of individuals, there is evidence that interhemispheric connectivity is altered both at the level of structural integrity and functional connectivity (FC).…”

Section: Introductionmentioning

confidence: 99%

CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility

et al. 2023

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Functional and structural connectivity alterations in short- and long-range projections have been reported across neurodevelopmental disorders (NDD). Interhemispheric callosal projection neurons (CPN) represent one of the major long-range projections in the brain, which are particularly important for higher-order cognitive function and flexibility. However, whether a causal relationship exists between interhemispheric connectivity alterations and cognitive deficits in NDD remains elusive. Here, we focused on CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the X-linked Cyclin-dependent kinase-like 5 (CDKL5) gene. We found an increase in homotopic interhemispheric connectivity and functional hyperconnectivity across higher cognitive areas in adult male and female CDKL5-deficient mice by resting-state functional MRI (rs-fMRI) analysis. This was accompanied by an increase in the number of callosal synaptic inputs but decrease in local synaptic connectivity in the cingulate cortex of juvenile CDKL5-deficient mice, suggesting an impairment in excitatory synapse development and a differential role of CDKL5 across excitatory neuron subtypes. These deficits were associated with significant cognitive impairments in CDKL5 KO mice. Selective deletion of CDKL5 in the largest subtype of CPN likewise resulted in an increase of functional callosal inputs, without however significantly altering intracortical cingulate networks. Notably, such callosal-specific changes were sufficient to cause cognitive deficits. Finally, when CDKL5 was selectively re-expressed only in this CPN subtype, in otherwise CDKL5-deficient mice, it was sufficient to prevent the cognitive impairments of CDKL5 mutants. Together, these results reveal a novel role of CDKL5 by demonstrating that it is both necessary and sufficient for proper CPN connectivity and cognitive function and flexibility, and further validates a causal relationship between CPN dysfunction and cognitive impairment in a model of NDD.

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The functional characterization of callosal connections

Cited by 41 publications

References 310 publications

Retrospective analysis of 21 cases of Marchiafava-Bignami disease in alcoholic in Southwest China

Retrospective analysis of 21 cases of Marchiafava-Bignami disease in alcoholic in Southwest China

Inefficient white matter activity in Schizophrenia evoked during intra and inter-hemispheric communication

CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility

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