Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in interhemispheric communication may impair gait coordination which is modulated by communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of interhemispheric communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of interhemispheric inhibition and how it relates to gait adaptation in PwMS. METHODS: Using transcranial magnetic stimulation (TMS), we assessed interhemispheric inhibition differences between the more affected and less affected hemisphere in the primary motor cortices in 29 PwMS. In addition, these same PwMS underwent a split-belt treadmill walking paradigm, with the faster paced belt moving under their more affected limb. Step length asymmetry (SLA) was the primary outcome measure used to assess gait adaptability during split-belt treadmill walking. We hypothesized that PwMS would exhibit differences in iSP inhibitory metrics between the more affected and less affected hemispheres and that increased interhemispheric inhibition would be associated with greater gait adaptability in PwMS. RESULTS: No statistically significant differences in interhemispheric inhibition or conduction time were found between the more affected and less affected hemisphere. Furthermore, SLA aftereffect was negatively correlated with both average percent depth of silent period (dSP%AVE) (r = -0.40, p = 0.07) and max percent depth of silent period (dSP%MAX) r = -0.40, p = 0.07), indicating that reduced interhemispheric inhibition was associated with greater gait adaptability in PwMS. CONCLUSION: The lack of differences between the more affected and less affected hemisphere indicates that PwMS have similar interhemispheric inhibitory capacity irrespective of the more affected hemisphere. Additionally, we identified a moderate correlation between reduced interhemispheric inhibition and greater gait adaptability. These findings may indicate that interhemispheric inhibition may in part influence responsiveness to motor adaptation paradigms and the need for further research evaluating the neural mechanisms underlying the relationship between interhemispheric inhibition and motor adaptability.

Ideational Slippage in Middle-Aged and Older Adults: A Preliminary Study.

Ideational slippage-characterized by incorrect word usage and strained logic during dialogue-is common in aging and, at greater frequency, is an indicator of pre-clinical cognitive decline. Performance-based assessment of ideational slippage may be useful in the study of cognitive aging and Alzheimer's-disease-related pathology. In this preliminary study, we examine the association between corpus callosum volume and a performance-based assessment of ideational slippage in middle-aged and older adults (age 61-79 years). Ideational slippage was indexed from cognitive special scores using the Rorschach Inkblot Method (RIM), which are validated indices of deviant verbalization and logical inaccuracy (Sum6, WSum6). Among middle-aged and older adults, smaller splenium volume was associated with greater ideational slippage (ηp2 = 0.48), independent of processing speed and fluid intelligence. The observed negative associations are consistent with visuospatial perception and cognitive functions of the splenium. The effect was strongest with the splenium, and volumes of the genu and total white matter had small effects that were not statistically significant. Conclusions: Results are discussed with future application of RIM special scores for the assessment of pre-clinical cognitive decline and, based on observed effect sizes, power analyses are reported to inform future study planning.

Diverse axonal morphologies of individual callosal projection neurons reveal new insights into brain connectivity.

In the mature brain, functionally distinct areas connect to specific targets, mediating network activity required for function. New insights are still occurring regarding how specific connectivity occurs in the developing brain. Decades of work have revealed important insights into the molecular and genetic mechanisms regulating cell type specification in the brain. This work classified long-range projection neurons of the cerebral cortex into three major classes based on their primary target (e.g. subcortical, intracortical, and interhemispheric projections). However, painstaking single-cell mapping reveals that long-range projection neurons of the corpus callosum connect to multiple and overlapping ipsilateral and contralateral targets with often highly branched axons. In addition, their scRNA transcriptomes are highly variable, making it difficult to identify meaningful subclasses. This work has prompted us to reexamine how cortical projection neurons that comprise the corpus callosum are currently classified and how this stunning array of variability might be achieved during development.

Diverse and asymmetric patterns of single-neuron projectome in regulating interhemispheric connectivity.

The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric "heterogeneity" to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.

Dichotic listening and interhemispheric integration after callosotomy: A systematic review.

The right-ear advantage (REA) for recalling dichotically presented auditory-verbal stimuli has been traditionally linked to the dominance of the left cerebral hemisphere for speech processing. Early studies on patients with callosotomy additionally found that the removal of the corpus callosum leads to a complete extinction of the left ear, and consequently the today widely used models to explain the REA assume a central role of callosal axons for recalling the left-ear stimulus in dichotic listening. However, later dichotic-listening studies on callosotomy patients challenge this interpretation, as many patients appear to be able to recall left-ear stimuli well above chance level, albeit with reduced accuracy. The aim of the present systematic review was to identify possible experimental and patient variables that explain the inconsistences found regarding the effect of split-brain surgery on dichotic listening. For this purpose, a systematic literature search was conducted (databases: Pubmed, Web of Knowledge, EBSChost, and Ovid) to identify all empirical studies on patients with surgical section of the corpus callosum (complete or partial) that used a verbal dichotic-listening paradigm. This search yielded ks = 32 publications reporting patient data either on case or group level, and the data was analysed by comparing the case-level incidence of left-ear suppression, left-ear extinction, and right-ear enhancement narratively or statistically considering possible moderator variables (i.a., extent of the callosal surgery, stimulus material, response format, selective attention). The main finding was an increased incidence of left-ear suppression (odds ratio = 7.47, CI95%: [1.21; 83.49], exact p = .02) and right-ear enhancement (odds ratio = 21.61, CI95%: [4.40; 154.11], p < .01) when rhyming as compared with non-rhyming stimuli were used. Also, an increase in left-ear reports was apparent when a response by the right hemisphere was allowed (i.e., response with the left hand). While the present review is limited by the overall small number of cases and a lack of an appropriate control sample in most of the original studies, the findings nevertheless suggest an adjustment of the classical dichotic-listening models incorporating right-hemispheric processing abilities as well as the perceptual competition of the left- and right-ear stimuli for attention.

Equalizing transcallosal inhibition in the mouse anterior cingulate mitigates visuospatial neglect.

A recent study by Wang and colleagues disentangled a transcallosal inhibitory circuit in mouse anterior cingulate cortex (ACC), which modulates excitatory ipsilateral tonus and contralateral inhibition by exciting contralateral parvalbumin-positive (PV+) interneurons. The authors conclude that the identified circuit mediates interhemispheric balance for visuospatial attention and provides top-down modulation of visual cortices.

Differential Effects of Aging on Regional Corpus Callosum Microstructure and the Modifying Influence of Pulse Pressure.

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anteroposterior gradient of vulnerability to aging that may be altered by the effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age = 53.56 ± 18.90; range, 20-94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion-weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested the effects of age, hypertension, and pulse pressure on these cross-sectional metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age-pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed nonlinear components and occurred along an anteroposterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable and that pulse pressure, a proxy of arterial stiffness, exacerbates this aging pattern in a large lifespan cohort.

Heading during the season and its potential impact on brain structure and neurocognitive performance in high-level male football players: An observational study.

OBJECTIVES: To investigate potential effects of heading on the neurocognitive performance and the white matter (WM) of the brain in high-level adult male football players. DESIGN: Prospective longitudinal. METHODS: Football players engaging in the highest football leagues in Germany were included. Neurocognitive performance tests and diffusion tensor imaging (DTI) were executed before and after the observation period. Video recordings of each training session and each match play during the observation period were analyzed regarding heading exposure and characteristics. Four DTI measures from tract-based spatial statistics (fractional anisotropy, mean, axial, and radial diffusivity) were investigated. Associations between heading variables and DTI and neurocognitive parameters were tested subsequently. RESULTS: 8052 headers of 22 players (19.9 ±â€¯2.7 years) were documented in a median of 16.9 months. The individual total heading number ranged from 57 to 943 (median: 320.5). Header characteristics differed between training sessions and matches. Neurocognitive performance (n = 22) and DTI measures (n = 14) showed no significant differences from pre- to post-test. After correction for multiple comparisons, no significant correlations with the total heading number were found. However, the change in fractional anisotropy in the splenium of the corpus callosum correlated significantly with the total amount of long-distance headers (Pearson's r = -0.884; p < 0.0001). CONCLUSIONS: Over the median observation period of 16.9 months, DTI measures and neurocognitive performance remained unchanged. To elucidate the meaning of the association between individual change in fractional anisotropy and long-distance headers further investigations with larger samples, longer observations, and various cohorts regarding age and level of play are required.

El papel del cuerpo calloso en el procesamiento visoespacial / The role of the corpus callosum in the visuospatial processing

El procesamiento visoespacial es una función adaptativa del organismo que permite su interacción con los elementos que se encuentran en su medio ambiente. Se considera una función superior, ya que involucra sistemas de reconocimiento y de memoria, entre otros. Hasta el momento se ha descrito la participación de diversas estructuras cerebrales en el procesamiento de información visoespacial, por ejemplo, tradicionalmente se considera una especialización funcional por parte del hemisferio derecho; sin embargo aún existen muchas controversias con respecto a la participación de diversas áreas cerebrales tanto ipsilaterales como contralaterales en estás funciones visoespaciales. En el presente trabajo se discute el papel de la comunicación interhemisferica, y específicamente del papel que juega el cuerpo calloso en el procesamiento visoespacial. Se inicia con una descripción de las vías de procesamiento visoespacial desde el ojo hasta la corteza V1 y las conexiones anatómicas funcionales que se establecen a partir de ésta. Posteriormente se resume la estructura-función del cuerpo calloso y se revisan los trabajos que han reportado relaciones entre éste y la función visoespacial. Por último, se revisan algunas de las patologías neurológicas que cursan con afectación del cuerpo calloso y que se ha reportado en la literatura que afectan a la función visoespacial...

The visuospatial processing is an adaptive function of the organism that allows it to interact with the elements that are in their environment. It is considered a high-order function as it involves recognition systems, memory, among others. So far described the participation of various brain structures in processing visuospatial information, for example, is traditionally considered a functional specialization by the right hemisphere, but there are still many controversies regarding the participation of various brain areas, both ipsilateral and contralateral in the visuospatial functions. In this paper we discuss the role of interhemispheric communication, and specifically the role of the corpus callosum in visuospatial processing. It begins with a description of visuospatial processing pathways from the eye to the cortex V1 and the anatomical-functional connections are established from this. Later summarizes the structure-function of the corpus callosum and reviews the studies that have reported relationships between this and visuospatial function. Finally we review some of the neurological disorders that present with involvement of the corpus callosum and it has been reported in the literature that affect visuospatial function...

Anatomy of corpus callosum in prenatally malnourished rats

The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particulary in visual connections (splenium).

Música y cerebro (II): evidencias cerebrales del entrenamiento musical / Music and brain (II): evidence of musical training in the brain

La música es un estímulo multimodal muy potente que transmite información visual, auditiva y motora a nuestrocerebro, el cual cuenta con una red específica para su procesamiento, compuesta por regiones fronto-temporoparietales. Esta activación puede resultar muy provechosa en el tratamiento de diversos síndromes y enfermedades, ya sea rehabilitando o bien estimulando conexiones neuronales alteradas. Revisamos también las peculiaridades del cerebro del músico y vemos cómo el cerebro se adapta según las necesidades para mejorar su ejecución musical (AU)

Music is a very powerful multimodal stimulus that transmits visual, auditory and motor information to our brain, which in turn has a specific network for processing it, consisting in the frontotemporoparietal regions. This activation can be very beneficial in the treatment of several syndromes and diseases, either by rehabilitating or by stimulating altered neuronal connections. We also review the peculiarities of the musician’s brain and we look at how the brain adapts according to the needs that must be met in order to improve musical performance (AU)

Electrophysiological evidence for an L-shaped interhemispheric connection in the cat

Transcallosal potentials evoked by electrical stimulation with rectangular pulses of 1 ms, 5 c/s and variable intensity were recorded from the cortical surface in cats anesthetized with ketamine hydrochloride. Sites of stimulation and recording were selected by means of a cartesian map of most of neocotex. In addition to the well known transcallosal projection pattern it was faund that stimulation of a restricted posterior area evokes low voltage potentials over the contralateral symmetric area while high voltage potentials are recorded from a few sites located at the ipsilateral anterior cortex and from the area symmetric as to the latter. This L-shaped transcallosal connection may be involved in complex cortical processes and is compatible with effective results of partial anterior callosotomies in patients whit multifocal epilepsy and frontal bisynchronism

Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization

Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.

An evoked potential mapping of transcallosal projections in the cat

Em dez gatos anestesiados com cetamina (Ketalar) o neocórtex foi exposto e pulsos retangulares (1 ms, 0,5Hz e intensidade variável) foram aplicados a pontos discretos de um lado enquanto se registravam os potenciais evocados no outro lado. As posiçöes de estimulaçäo e registro eram determinadas em mapa cartesiano que abrangia quase todo o neocórtex. Os potenciais foram analisados quanto aos dseus componentes, voltagem e latência. A difusäo passiva, potenciais eletrotônicos e e os efeitos do incremento da freqüência de estimulaçäo sobre os vários componentes foram analisados. Os resultados mostram a presença de grandes potenciais evocados transcalosos em algumas regiöes, com incremento de sua amplitude no sentido caudo-rostral, sendo máximos em áreas anteromediais do giro suprasilviano. Confirmando estudos anatômicos, em algumas regiöes do córtex somatomotor e visual foram registrados potenciais bastante reduzidos ou ausentes. A estimulaçäo de algumas áreas posteriores causava o aparecimento de pequenos potenciais em sua área homóloga contralateral ao mesmo tempo em que grandes potenciais eram registrados em áreas anteriores ipsi- e contralateralmente, constituindo uma conexäo em L ainda näo descrita. É possível que tal conexäo esteja implicada em alguns tipos de epilepsia e possa explicar em parte a eficácia de calosotomias parciais para seu tratamento

Tumor del cuerpo calloso: asociación de la desconexión interhemisférica con un síndrome de amnesia anterógrada / Tumour of the corpus callosum: the association between interhemispheric disconnection and an anterograde amnesia syndrome

Introducción. El síndrome de Sperry o de desconexióninterhemisférica se describió en pacientes con sección quirúrgicadel cuerpo calloso realizada para controlar la epilepsia refractariaal tratamiento farmacológico. Ocasionalmente se ha relacionadocon tumores del cuerpo calloso, y es más raro verlo asociado con unsíndrome amnésico. En este artículo se describen los hallazgos anatómicosy neuropsicológicos de un paciente con síndrome de desconexióninterhemisférica asociado a un síndrome amnésico de tipohipocampal, secundarios a un tumor del esplenio del cuerpo callosoque invadió el fórnix. Caso clínico. Hombre blanco de 52 añosque consultó por pérdida de la memoria; al ingreso, el examen físicoreveló cierto grado de asomatognosia en el hemicuerpo izquierdo.La tomografía axial del cráneo mostró una lesión central densaen el cerebro que se extendía lateralmente y ocluía el cuerpo deambos ventrículos laterales. La biopsia reveló un astrocitoma indiferenciadoque afectaba al cuerpo calloso y al fórnix. Conclusiones.El síndrome de Sperry o de desconexión interhemisférica producidopor un tumor del esplenio del cuerpo calloso tiene una probabilidadalta de cursar además con un síndrome amnésico por desconexión,causado por la destrucción del fórnix. Esta asociación, que caracterizabael cuadro clínico de nuestro paciente, se ha indicado previamentesólo en tres casos

Introduction. Sperry, or interhemispheric disconnection, syndrome was reported in patients who had undergonesurgical section of the corpus callosum carried out in an attempt to control medication-resistant epilepsy. It has occasionallybeen linked to tumours of the corpus callosum and, although even more rarely, it has also been associated to an amnesicsyndrome. In this paper we report the anatomical and neuropsychological findings in a patient with interhemispheric disconnectionsyndrome associated to a hippocampal-type amnesic syndrome, caused by a tumour in the splenius of the corpuscallosum that extended into the fornix. Case report. A 52-year-old white male who visited because of loss of memory; onadmission to hospital the physical examination revealed a certain degree of asomatognosia with regard to the left-hand side ofthe body. An axial tomography brain scan showed a dense central lesion in the brain that extended laterally and occluded thebody of both lateral ventricles. A biopsy study revealed an undifferentiated astrocytoma that affected the corpus callosum andthe fornix. Conclusions. Sperry, or interhemispheric disconnection, syndrome produced by a tumour in the splenius of thecorpus callosum is very likely to course with an amnesic syndrome due to disconnection caused by destruction of the fornix.This association, which characterised our patient’s clinical picture, has only previously been described in three cases

Brain connections: interhemispheric fiber systems and anatomical brain asymmetries in humans

The present review summarizes some results of a research program oriented to determine the anatomical substrates of interhemispheric communication in humans, as seen in postmortem material. One main finding is a sensible pattern of histological differentiation along the corpus callosum, indicating specific properties of interhemispheric conduction for axonal fibers involved in different brain functions. Callosal regions that connect primary and secondary sensory and motor areas are characterized by a large proportion of fast-conducting, large-diameter fibers, while regions connecting the so-called association areas and prefrontal areas bear a high density of slow-conducting, lightly myelinated and thin fibers. These findings are interpreted in a functional context, suggesting that the fast-conducting fibers connecting sensory and motor areas contribute to fuse the two hemirepresentations in each hemisphere. It has also been determined that an increased callosal area indicates an increased number of callosal fibers, a finding that validates previous morphometric studies done in several laboratories. No sex differences in callosal size, shape, or in callosal fiber composition were found. Finally, an inverse relation was found between the anatomical asymmetries in the size of the Sylvian fissure and the size and number of fibers in specific segments of the corpus callosum. There were sex differences in terms of the particular callosal regions showing a significant correlation with asymmetries, and in terms of the fiber types that were correlated with asymmetries