Callosal Connections Research Articles

P244 The effect of transcranial direct current stimulation on motor sequence learning and upper limb function after stroke

Transcranial direct current stimulation (tDCS) is a safe and non-invasive brain stimulation technique with the potential to improve upper limb function after stroke. Ipsilesional primary motor cortex (M1) excitability can be increased with anodal tDCS, contralesional M1 excitability can be decreased with cathodal tDCS or both anodal and cathodal tDCS can be used simultaneously on both cortices (bihemispheric). The impact of these different electrode arrangements on the efficacy of tDCS, and whether any of the changes are due to callosal connections between cortices, is unclear. This study aimed to investigate the effect of tDCS electrode arrangement on motor sequence learning and upper limb function in chronic stroke survivors. 21 stroke survivors (range 3–124 months post-stroke, 34–81 years of age) with upper limb impairment received 20 min of 1 mA tDCS (0.04 mA·cm−2) during performance of a motor sequence learning task which involved movement of a computer mouse with the paretic arm to circular targets on a monitor in a repeating pattern. Four tDCS conditions were studied in a repeated-measures design; (i) anodal to the ipsilesional M1, (ii) cathodal to the contralesional M1, (iii) bihemispheric and (iv) sham. Upper limb function was assessed before and after tDCS, using the Jebsen–Taylor hand function test (JTT). Changes in transcallosal inhibition (TCI) were assessed using transcranial magnetic stimulation (ipsilateral silent period duration). There was no effect of tDCS condition on performance of the motor sequence learning task. Performance on the JTT improved significantly after unilateral tDCS (anodal or cathodal) compared to sham (p < 0.05), but not after bihemispheric (Fig. 1). There was no effect on TCI (p > 0.5), and no relationship between changes in TCI and upper limb function. Unilateral, but not bihemispheric, tDCS improves upper limb function. The response to tDCS does not appear to be driven by changes in TCI. These results have implications for the use of tDCS for upper limb rehabilitation.Download : Download high-res image (77KB)Download : Download full-size image

ROBO1 polymorphisms, callosal connectivity, and reading skills.

The genetic effects on specific behavioral phenotypes are putatively mediated by specific neural functions. It remains unexplored how the axon-guidance-receptor gene ROBO1 influences reading performance through the neural system despite the identification of ROBO1 as a susceptibility gene for dyslexia. To address this issue, the present study recruited a group of children with a wide range of reading abilities. Two previously identified reading-related ROBO1 polymorphisms were genotyped, and diffusion and structural MRI were acquired to measure the fiber microstructure of the corpus callosum (CC), the major white-matter tract that connects inter-hemispheric cortical regions. The results confirmed the significant influence of the ROBO1 polymorphisms on reading scores. The fiber microstructures of the midline-CC segments around the genu and splenium were also affected by the ROBO1 polymorphisms. Moreover, a mediation analysis further revealed that the genu could significantly mediate the effects of the ROBO1 polymorphisms on word-list reading performance, which suggests a ROBO1-to-genu-to-reading pathway. The genu-linked cortical morphology, however, was not associated with either the ROBO1 polymorphisms or reading performance. These findings offer direct evidence supporting ROBO1-callosum association in humans and also provide valuable insight into the functions of ROBO1 and the gene-to-brain mechanisms that underlie human reading. Hum Brain Mapp 38:2616-2626, 2017. © 2017 Wiley Periodicals, Inc.

Mental State Understanding in Children with Agenesis of the Corpus Callosum.

Impaired social functioning is a well-known outcome of individuals with agenesis of the corpus callosum. Social deficits in nonliteral language comprehension, humor, social reasoning, and recognition of facial expression have all been documented in adults with agenesis of the corpus callosum. In the present study, we examined the emotional and mentalizing deficits that contributing to the social-cognitive development in children with isolated corpus callosum agenesia, including emotion recognition, theory of mind, executive function, working memory, and behavioral impairments as assessed by the parents. The study involved children between the age of 6 and 8 years along with typically developing children who were matched by IQ, age, gender, education, and caregiver's education. The findings indicated that children with agenesis of the corpus callosum exhibited mild impairments in all social factors (recognizing emotions, understanding theory of mind), and showed more behavioral problems than control children. Taken together, these findings suggest that reduced callosal connectivity may contribute to the development of higher-order social-cognitive deficits, involving limits of complex and rapidly occurring social information to be processed. The studies of AgCC shed lights of the role of structural connectivity across the hemispheres in neurodevelopmental disorders.

Distant heterotopic callosal connections to premotor cortex in non-human primates

Cortico-cortical connectivity has become a major focus of neuroscience in the last decade but most of the connectivity studies focused on intrahemispheric circuits. Little has been reported about information acquired and processed in the premotor cortex and its functional connection with its homotopic counterpart in the opposite hemisphere via the corpus callosum. In non-human primates (macaques) lateralization is not well documented and its exact role is still unknown. The present study confirms in two macaques the existence of homotopic contralateral projections and completes the picture by further exploring heterotopic (non-motor) callosal projections. This was tested by injecting retrograde tracers in the premotor cortical areas PMv and PMd (targets). Our method consisted of identifying the connections with all the homo- and heterotopic cortical areas located in the contralateral hemisphere. The results showed that PMd and PMv receive multiple low-density labeled inputs from the opposite heterotopic prefrontal, parietal, motor, insular and temporal regions. Such unexpected collection of transcallosal inputs from heterotopic areas suggests that the premotor areas communicate with other modalities through long distance low-density networks which could have important implications in the understanding of sensorimotor and multimodal integration.

Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0278-3) contains supplementary material, which is available to authorized users.

Development of Proprioceptive Acuity in Typically Developing Children: Normative Data on Forearm Position Sense.

This study mapped the development of proprioception in healthy, typically developing children by objectively measuring forearm position sense acuity. We assessed position sense acuity in a cross-sectional sample of 308 children (5–17 years old; M/F = 127/181) and a reference group of 26 healthy adults (18–25 years old; M/F = 12/14) using a body-scalable bimanual manipulandum that allowed forearm flexion/extension in the horizontal plane. The non-dominant forearm was passively displaced to one of three target positions. Then participants actively matched the target limb position with their dominant forearm. Each of three positions was matched five times. Position error (PE), calculated as the mean difference between the angular positions of the matching and reference arms, measured position sense bias or systematic error. The respective standard deviation of the differences between the match and reference arm angular positions (SDPdiff) indicated position sense precision or random error. The main results are as follows: First, systematic error, measured by PE, did not change significantly from early childhood to late adolescence (Median PE at 90° target: −2.85° in early childhood; −2.28° in adolescence; and 1.30° in adults). Second, response variability as measured by SDPdiff significantly decreased with age (Median SDPdiff at 90° target: 9.66° in early childhood; 5.30° in late adolescence; and 3.97° in adults). The data of this large cross-sectional sample of children document that proprioceptive development in typically developing children is characterized as an age-related improvement in precision, not as a development or change in bias. In other words, it is the reliability of the perceptual response that improves between early childhood and adulthood. This study provides normative data against which position sense acuity in pediatric patient populations can be compared. The underlying neurophysiological processes that could explain the observed proprioceptive development include changes in the tuning of muscle spindles at the spinal level, the maturation of supraspinal somatosensory pathways and the development of interhemispheric callosal connections responsible for the transfer of somatosensory information.

Proverb comprehension in individuals with agenesis of the corpus callosum

Comprehension of non-literal language involves multiple neural systems likely involving callosal connections. We describe proverb comprehension impairments in individuals with isolated agenesis of the corpus callosum (AgCC) and normal-range general intelligence. Experiment 1 compared Gorham Proverb Test (Gorham, 1956) performance in 19 adults with AgCC and 33 neurotypical control participants of similar age, sex, and intelligence. Experiment 2 used the Proverbs subtest of the Delis-Kaplan Executive Function System (D-KEFS, 2001) to compare 19 adults with AgCC and 17 control participants with similar age, sex, and intelligence. Gorham Proverbs performance was impaired in the AgCC group for both the free-response and multiple-choice tasks. On the D-KEFS proverbs test, the AgCC group performed significantly worse on the free-response task (and all derivative scores) despite normal levels of performance on the multiple-choice task. Covarying verbal intelligence did not alter these outcomes. However, covarying a measure of non-literal language comprehension considerably reduced group differences in proverb comprehension on the Gorham test, but had little effect on the D-KEFS group differences. The difference between groups seemed to be greatest when participants had to generate their own interpretation (free response), or in the multiple choice format when the test included many proverbs that were likely to be less familiar. Taken together, the results of this study clearly show that proverb comprehension is diminished in individuals with AgCC compared to their peers.

Axon diameter relates to synaptic bouton size: structural properties define computationally different types of cortical connections in primates.

Neural connections are implemented by axons of different diameters, whose spectrum increases depending on species and areas. Axon diameter determines conduction velocity and is proportional to the size of the cell body of origin. We describe that in motor, callosal connections of the monkey thick axons distribute larger boutons than thin axons, suggesting that faster axons also release more neurotransmitter at their termination, probably activating more powerfully their targets.

White matter microstructural properties correlate with sensorimotor synchronization abilities

Sensorimotor synchronization (SMS) to an external auditory rhythm is a developed ability in humans, particularly evident in dancing and singing. This ability is typically measured in the lab via a simple task of finger tapping to an auditory beat. While simplistic, there is some evidence that poor performance on this task could be related to impaired phonological and reading abilities in children. Auditory-motor synchronization is hypothesized to rely on a tight coupling between auditory and motor neural systems, but the specific pathways that mediate this coupling have not been identified yet. In this study, we test this hypothesis and examine the contribution of fronto-temporal and callosal connections to specific measures of rhythmic synchronization. Twenty participants went through SMS and diffusion magnetic resonance imaging (dMRI) measurements. We quantified the mean asynchrony between an auditory beat and participants' finger taps, as well as the time to resynchronize (TTR) with an altered meter, and examined the correlations between these behavioral measures and diffusivity in a small set of predefined pathways. We found significant correlations between asynchrony and fractional anisotropy (FA) in the left (but not right) arcuate fasciculus and in the temporal segment of the corpus callosum. On the other hand, TTR correlated with FA in the precentral segment of the callosum. To our knowledge, this is the first demonstration that relates these particular white matter tracts with performance on an auditory-motor rhythmic synchronization task. We propose that left fronto-temporal and temporal-callosal fibers are involved in prediction and constant comparison between auditory inputs and motor commands, while inter-hemispheric connections between the motor/premotor cortices contribute to successful resynchronization of motor responses with a new external rhythm, perhaps via inhibition of tapping to the previous rhythm. Our results indicate that auditory-motor synchronization skills are associated with anatomical pathways that have been previously related to phonological awareness, thus offering a possible anatomical basis for the behavioral covariance between these abilities.

Ipsilateral Hemichorea-hemiballism in a Case of Postoperative Stroke.

BackgroundIpsilateral hemiballismus refers to the rare occurrence of hemiballism developing on the same side of a brain lesion.Case reportWe describe a rare case of postoperative ipsilateral hemiballism in a patient who underwent pituitary adenoma resection and experienced a right internal cerebral artery territory infarct. We review the literature on hemichorea hemiballismus (HCHB) and explore various mechanisms for its occurrence.DiscussionOnly three cases of ipsilateral hemiballism have been described, and the exact pathophysiology remains unknown. A dominant left hemisphere with corpus callosal connections to the right basal ganglia is the most probable explanation for this unusual event.

Heterogeneity of trans-callosal structural connectivity and effects on resting state subnetwork integrity may underlie both wanted and unwanted effects of therapeutic corpus callostomy.

BackgroundThe corpus callosum (CC) is the primary structure supporting interhemispheric connectivity in the brain. Partial or complete surgical callosotomy may be performed for the palliation of intractable epilepsy. A variety of disconnection syndromes are recognised after injury to or division of the CC however their mechanisms are poorly understood and their occurrence difficult to predict. We use novel high resolution structural connectivity analyses to demonstrate reasons for this poor predictability.MethodsDiffusion weighted MRI data from five healthy adult controls was subjected to novel high-resolution structural connectivity analysis. We simulated the effects of CC lesions of varying extents on the integrity of resting state subnetworks (RSNs).ResultsThere is substantial between-individual variation in patterns of CC connectivity. However in all individuals termination points of callosal connections mostly involve medial and superior sensory-motor areas. Superior temporal and lateral sensory-motor areas were not involved. Resting state networks showed selective vulnerability to simulated callosotomy of progressively greater anterior to posterior extent. The default mode network was most vulnerable followed by, in decreasing order: frontoparietal, limbic, somatomotor, ventral attention, dorsal attention and visual subnetworks.ConclusionConsideration of the selective vulnerability of resting state sub-networks, and of between-individual variability in connectivity patterns, sheds new light on the occurrence of both wanted and unwanted effects of callosotomy. We propose that beneficial effects (seizure reduction) relate to disruption of the default mode network, with unwanted “disconnection syndrome” effects due to disruption particularly of the somatomotor and frontoparietal RSNs. Our results may also explain why disconnection syndromes primary reflect lateralised sensory-motor problems (e.g. of limb movement) rather than midline function (e.g. tongue movement). Marked between-subject variation in callosal connectivity may underlie the poor predictability of effects of callosotomy. High resolution structural connectivity studies of this nature may be useful in pre-surgical planning of therapeutic callosotomy for intractable epilepsy.

Filamin A interacting protein plays a role in proper positioning of callosal projection neurons in the cortex

The callosal connections between the two hemispheres of the neocortex are altered in certain psychiatric disorders including schizophrenia. However, how and why the callosal connection is impaired in patients suffering from psychiatric diseases remain unclear. Filamin A interacting protein (FILIP), whose alteration through mutation relates to schizophrenic pathogenesis, binds to actin-binding proteins and controls neurotransmission. Because cortical excitatory neurons, including callosal projection neurons, migrate to the cortical plate during development, with the actin-binding proteins playing crucial roles during migration, we evaluated whether FILIP is involved in the development of the callosal projection neurons by histological analysis of Filip-knockout mice. The positioning of the callosal projection neurons, especially those expressing Plxnd1, in the superficial layer of the cortex is disturbed in these mice, which suggests that FILIP is a key molecule that links callosal projections to the pathogenesis of brain disorders.

The origins of strabismus and loss of binocular vision. Implication of the corpus callosum

SummaryStrabismus and loss of binocular vision (BV) are often linked disorders because the parallelism of the eyes is necessary for a proper BV. But no BV may exist in the absence of strabismus. If the question of the consequences of strabismus and loss of BV on the brain has been explored for decades, the core question of their origins is less understood. Strabismus is a developmental disorder which causes are numerous as assessed by the various forms of strabismus. Peripheral causes are sometimes responsible. But central causes are mostly the primum movens of strabismus and loss of BV. Normal interhemispheric callosal connections (CC) being necessary for a proper unification of both visual hemifields and for normal BV along the vertical meridian, we propose here that an abnormal development of the CC might be responsible for strabismus and loss of BV. A misrouting of ganglion cell axons or abnormal development of neuronal activity in the visual system or abnormal development of neuronal activity in the oculomotor system are also proposed to be implicated.ReferenceBui Quoc E, Milleret C. Origins of strabismus and loss of binocular vision. Front Integr Neurosci. 2014 Sep 25;8:71. doi: 10.3389/fnint.2014.00071. eCollection 2014.

Normal vision, strabismus and the corpus callosum in animals

SummaryIn the primary visual cortex of higher mammals, both the retino‐geniculo‐cortical (RGC) and the interhemispheric callosal pathways contribute to the unification of the visual hemifields that project separately within the two hemispheres. Anatomical and functional studies performed on animals reveal that each pathway complements each other both spatially and in terms of binocularity. They also reveal that this pattern emerges progressively with age during the critical period, proving however postnatal visual experience has been normal. In case of abnormal postnatal vision such as the one led by strabismus, both pathways develop abnormally. In particular, we have shown recently that asymmetrical callosal connections develop and this prevents the establishment of a unifying representation of the two visual hemifields. As a general rule, we suggest that crossed and uncrossed RGC pathways contribute successively to all this.ReferenceC. Milleret et al. Eur. J. Neurosci. 1994, 6:193; JC Houzel et al. 1994, Eur. J. Neurosci. 6: 898; C. Milleret &amp; J.C. Houzel. Eur. J. Neurosci. 2001, 13:137; N. Rochefort et al. Neuroimage, 2007, 36:804; E. Bui Quoc et al. Frontiers in Neuroanat. 2011, 5: 1‐29; Ribot et al. J. Neurosci. 2013, 33:13326.

Abnormal interhemispheric motor interactions in patients with callosal agenesis

During unilateral hand movements the activity of the contralateral primary motor cortex (cM1) is increased while the activity of the ipsilateral M1 (iM1) is decreased. A potential explanation for this asymmetric activity pattern is transcallosal cM1-to-iM1 inhibitory control. To test this hypothesis, we examined interhemispheric motor inhibition in acallosal patients. We measured fMRI activity in iM1 and cM1 in acallosal patients during unilateral hand movements and compared their motor activity pattern to that of healthy controls. In controls, fMRI activation in cM1 was significantly higher than in iM1, reflecting a normal differential task-related M1 activity. Additional functional connectivity analysis revealed that iM1 activity was strongly suppressed by cM1. Furthermore, DTI analysis indicated that this contralaterally induced suppression was mediated by microstructural properties of specific callosal fibers interconnecting both M1s. In contrast, acallosal patients did not show a clear differential activity pattern between cM1 and iM1. The more symmetric pattern was due to an elevated task-related iM1 activity in acallosal patients, which was significantly higher than iM1 activity in a subgroup of gender and age-matched controls. Also, interhemispheric motor suppression was completely absent in acallosal patients. These findings suggest that absence of callosal connections reduces inhibitory interhemispheric motor interactions between left and right M1. This effect may reveal novel aspects of mechanisms in communication of two hemispheres and establishment of brain asymmetries in general.

Inter-hemispheric integration of tactile-motor responses across body parts.

In simple detection tasks, reaction times (RTs) are faster when stimuli are presented to the visual field or side of the body ipsilateral to the body part used to respond. This advantage, the crossed-uncrossed difference (CUD), is thought to reflect inter-hemispheric interactions needed for sensorimotor information to be integrated between the two cerebral hemispheres. However, it is unknown whether the tactile CUD is invariant when different body parts are stimulated. The most likely structure mediating such processing is thought to be the corpus callosum (CC). Neurophysiological studies have shown that there are denser callosal connections between regions that represent proximal parts of the body near the body midline and more sparse connections for regions representing distal extremities. Therefore, if the information transfer between the two hemispheres is affected by the density of callosal connections, stimuli presented on more distal regions of the body should produce a greater CUD compared to stimuli presented on more proximal regions. This is because interhemispheric transfer of information from regions with sparse callosal connections will be less efficient, and hence slower. Here, we investigated whether the CUD is modulated as a function of the different body parts stimulated by presenting tactile stimuli unpredictably on body parts at different distances from the body midline (i.e., Middle Finger, Forearm, or Forehead of each side of the body). Participants detected the stimulus and responded as fast as possible using either their left or right foot. Results showed that the magnitude of the CUD was larger on the finger (~2.6 ms) and forearm (~1.8 ms) than on the forehead (≃0.9 ms). This result suggests that the interhemispheric transfer of tactile stimuli varies as a function of the strength of callosal connections of the body parts.

Input and output gain modulation by the lateral interhemispheric network in early visual cortex.

Neurons in the cerebral cortex are constantly integrating different types of inputs. Dependent on their origin, these inputs can be modulatory in many ways and, for example, change the neuron's responsiveness, sensitivity, or selectivity. To investigate the modulatory role of lateral input from the same level of cortical hierarchy, we recorded in the primary visual cortex of cats while controlling synaptic input from the corresponding contralateral hemisphere by reversible deactivation. Most neurons showed a pronounced decrease in their response to a visual stimulus of different contrasts and orientations. This indicates that the lateral network acts via an unspecific gain-setting mechanism, scaling the output of a neuron. However, the interhemispheric input also changed the contrast sensitivity of many neurons, thereby acting on the input. Such a contrast gain mechanism has important implications because it extends the role of the lateral network from pure response amplification to the modulation of a specific feature. Interestingly, for many neurons, we found a mixture of input and output gain modulation. Based on these findings and the known physiology of callosal connections in the visual system, we developed a simple model of lateral interhemispheric interactions. We conclude that the lateral network can act directly on its target, leading to a sensitivity change of a specific feature, while at the same time it also can act indirectly, leading to an unspecific gain setting. The relative contribution of these direct and indirect network effects determines the outcome for a particular neuron.

Left-hemisphere lateralization for language and interhemispheric fiber tracking in patients with schizophrenia

BackgroundIt has been suggested that the degree of hemispheric specialization (HS) depends on the structural connectivity between the two hemispheres, that is to say the corpus callosum (CC). Studies, performed only on healthy participants, investigated this anatomo-functional relationship. Nevertheless, it has never been studied in schizophrenia. We therefore propose to study the anatomo-functional relationships between the integrity of interhemispheric connectivity and leftward functional lateralization for language in patients with schizophrenia compared with healthy participants, driven by a multimodal approach combining fMRI and DTI-based fiber tractography. We hypothesized that reduced leftward functional lateralization for language in patients with schizophrenia could be related to a callosal hypoconnectivity. Materials and methodsSeventeen patients based on the DSM-IV, and 17 controls were included. The functional laterality index and interhemispheric diffusion values between homologue temporal regions, belonging to the language network, were individually extracted in order to study the anatomo-functional relationships. ResultsIn the patients, higher mean and radial diffusivity (RD) values (thicker myelin sheaths) were associated with less leftward lateralization. In contrast, the controls presented higher RD values and lower fractional anisotropy values (axonal loss) with more leftward lateralization. ConclusionsOur study revealed a relationship between the CC and the HS for language, but did not provide evidence clarifying the direction of the relationship between callosal connectivity and functional lateralization for language. In particular, the present findings showed that the loss of integrity in interhemispheric callosal fibers was associated with reduced leftward cerebral dominance for language in patients with schizophrenia.

Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder.

BackgroundAutism spectrum disorders (ASD) are a group of poorly understood behavioural disorders, which have increased in prevalence in the past two decades. Animal models offer the opportunity to understand the biological basis of these disorders. Studies comparing different mouse strains have identified the inbred BTBR T + tf/J (BTBR) strain as a mouse model of ASD based on its anti-social and repetitive behaviours. Adult BTBR mice have complete agenesis of the corpus callosum, reduced cortical thickness and changes in early neurogenesis. However, little is known about the development or ultimate organisation of cortical areas devoted to specific sensory and motor functions in these mice that may also contribute to their behavioural phenotype.ResultsIn this study, we performed diffusion tensor imaging and tractography, together with histological analyses to investigate the emergence of functional areas in the cerebral cortex and their connections in BTBR mice and age-matched C57Bl/6 control mice. We found evidence that neither the anterior commissure nor the hippocampal commissure compensate for the loss of callosal connections, indicating that no interhemispheric neocortical connectivity is present in BTBR mice. We also found that both the primary visual and somatosensory cortical areas are shifted medially in BTBR mice compared to controls and that cortical thickness is differentially altered in BTBR mice between cortical areas and throughout development.ConclusionsWe demonstrate that interhemispheric connectivity and cortical area formation are altered in an age- and region-specific manner in BTBR mice, which may contribute to the behavioural deficits previously observed in this strain. Some of these developmental patterns of change are also present in human ASD patients, and elucidating the aetiology driving cortical changes in BTBR mice may therefore help to increase our understanding of this disorder.Electronic supplementary materialThe online version of this article (doi:10.1186/s13064-015-0033-y) contains supplementary material, which is available to authorized users.

Visual Interhemispheric and Striate-Extrastriate Cortical Connections in the Rabbit: A Multiple Tracer Study.

Previous studies in rabbits identified an array of extrastriate cortical areas anatomically connected with V1 but did not describe their internal topography. To address this issue, we injected multiple anatomical tracers into different regions in V1 of the same animal and analyzed the topography of resulting extrastriate labeled fields with reference to the patterns of callosal connections and myeloarchitecture revealed in tangential sections of the flattened cortex. Our results extend previous studies and provide further evidence that rabbit extrastriate areas resemble the visual areas in rats and mice not only in their general location with respect to V1 but also in their internal topography. Moreover, extrastriate areas in the rabbit maintain a constant relationship with myeloarchitectonic borders and features of the callosal pattern. These findings highlight the rabbit as an alternative model to rats and mice for advancing our understanding of cortical visual processing in mammals, especially for projects benefiting from a larger brain.