Biomedical subjects

L Krubitzer

Publications and source records attributed to L Krubitzer.

At least 19 recordsLinked to original sources

PubMed2006

Early blindness results in abnormal corticocortical and thalamocortical connections.

Studies in congenitally blind and bilaterally enucleated individuals show that an early loss of sensory driven activity can lead to massive functional reorganization. However, the anatomical substrate for this functional reorganization is unknown. In the present study, we examined patterns of corticocortical and thalamocortical connections in adult opossums that had been bilaterally enucleated neonatally, prior to the formation of retinogeniculate and geniculocortical connections. We show that in addition to normal thalamocortical projection patterns from visual nuclei, enucleated animals also receive input from nuclei associated with the somatosensory (ventral posterior nucleus, VP), auditory (medial geniculate nucleus, MGN), motor (ventrolateral nucleus, VL), and limbic/hippocampal systems (anterior dorsal nucleus, AD; and anterior ventral nucleus, AV). Likewise, in addition to normal corticocortical projections to area 17, bilaterally enucleated opossums also receive input from auditory, somatosensory, and multimodal cortex. These aberrant patterns of thalamocortical and corticocortical connections can account for alterations in functional organization observed in the visual cortex of bilateral enucleated animals, and indicate that factors extrinsic to the cortex play a large role in cortical field development and evolution. On the other hand, the maintenance of normal patterns of connections in the absence of visual input suggests that there are formidable constraints imposed on the developing cortex that highly restrict the types of evolutionary change possible.

Age Factors↗

PubMed2006

Multisensory plasticity in congenitally deaf mice: how are cortical areas functionally specified?

The neocortex of congenitally deaf mice was examined using electrophysiological recording techniques combined with cortical myeloarchitecture. Our results indicate that relative activity patterns across sensory systems during development contribute to modality assignment of cortical fields as well as the size of cortical fields. In congenitally deaf mice, "auditory cortex" contained neurons that responded to somatosensory, visual, or both somatosensory and visual stimulation; the primary visual area contained a larger proportion of neurons that responded to somatosensory stimulation than in normal animals, and the primary visual area had significantly increased in size. Thus, cortical architecture and functional specification were de-correlated. When results are considered in the light of molecular studies and studies in which peripheral activity is altered in development, it becomes clear that similar types of changes to the neocortex, such as alterations in cortical field size, can be achieved in more than one way in the developing and evolving neocortex.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Thalamo-cortical connections of areas 3a and M1 in marmoset monkeys.

The present investigation is part of a broader effort to examine cortical areas that contribute to manual dexterity, reaching, and grasping. In this study we examine the thalamic connections of electrophysiologically defined regions in area 3a and architectonically defined primary motor cortex (M1). Our studies demonstrate that area 3a receives input from nuclei associated with the somatosensory system: the superior, inferior, and lateral divisions of the ventral posterior complex (VPs, VPi, and VPl, respectively). Surprisingly, area 3a receives the majority of its input from thalamic nuclei associated with the motor system, posterior division of the ventral lateral nucleus of the thalamus (VL), the mediodorsal nucleus (MD), and intralaminar nuclei including the central lateral nucleus (CL) and the centre median nucleus (CM). In addition, sparse but consistent projections to area 3a are from the anterior pulvinar (Pla). Projections from the thalamus to the cortex immediately rostral to area 3a, in the architectonically defined M1, are predominantly from VL, VA, CL, and MD. There is a conspicuous absence of inputs from the nuclei associated with processing somatic inputs (VP complex). Our results indicate that area 3a is much like a motor area, in part because of its substantial connections with motor nuclei of the thalamus and motor areas of the neocortex (Huffman et al. [2000] Soc. Neurosci. Abstr. 25:1116). The indirect input from the cerebellum and basal ganglia via the ventral lateral nucleus of the thalamus supports its role in proprioception. Furthermore, the presence of input from somatosensory thalamic nuclei suggests that it plays an important role in somatosensory and motor integration.

Action Potentials↗

PubMed2001

Area 3a: topographic organization and cortical connections in marmoset monkeys.

The functional organization of area 3a, a cortical field proposed to be involved in somato-motor-vestibular integration, has never been described for any primate. In the present investigation, the topographic organization and connections of area 3a were examined in marmosets using electrophysiological recording and anatomical tracing techniques. Multi-unit neuronal activity was recorded at a number of closely spaced sites; receptive fields (RFs) for neurons were determined, and the optimal stimulus was identified. In all cases, neurons in area 3a responded to the stimulation of deep receptors on the contralateral body. The representation of the body in area 3a was from the toes and foot, to the hindlimb, trunk, forelimb, hand and face in a mediolateral progression. In all cases electrophysiological results were related to myeloarchitecture, and the map in area 3a was found to be coextensive with a strip of lightly to moderately myelinated cortex just rostral to the darkly myelinated 3b. To examine the cortical connections of area 3a, injections of anatomical tracers were made into electrophysiologically identified body part representations. Area 3a has dense intrinsic connections and receives substantial inputs from the primary motor cortex (M1), the supplementary motor area (SMA), areas 1 and 2, the second somatosensory area (S2), and areas in posterior parietal cortex (PP). The connections of area 3a indicate that integration of cortical representations of body parts occurs both within area 3a and between area 3a and other somatosensory and motor areas. In addition, there are differential patterns of interconnections between behaviorally relevant body part representations of area 3a, such as the forelimb, compared to other body part representations (hindlimb/ trunk), especially with 'higher order' cortical fields. This suggests that 3a may be an important component in a network that generates a common frame of reference for hand and eye coordinated reaching tasks.

Animals↗

PubMed2001

Evidence for interhemispheric processing of inputs from the hands in human S2 and PV.

In the present investigation, we identified cortical areas involved in the integration of bimanual inputs in human somatosensory cortex. Using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG), we compared the responses to unilateral versus bilateral stimulation in anterior parietal cortex and areas in the Sylvian fissure of the contralateral hemisphere. The extent of fMRI activation on the upper bank of the Sylvian fissure, in the second somatosensory (S2) and the parietal ventral (PV) areas, was significantly larger for bilateral stimulation than for unilateral stimulation. Using MEG, we were able to describe the latency of response in S1 and S2/PV to unilateral and bilateral stimulation. The MEG response had three components under both stimulus conditions. An early peak in S1 at 40 ms, a middle peak in S2/PV at 80-160 ms, and three late peaks in S2/PV at 250-420 ms. There was an increase in magnetic field strength in S2/PV to bilateral stimulation at 300-400 ms post stimulus. The fMRI results indicate that, as in monkeys, S2/PV receives inputs from both the contralateral and ipsilateral hand. The MEG data suggest that information is processed serially from S1 to S2. The very late response in S2/PV indicates that extensive intrahemispheric processing occurs before information is transferred to the opposite hemisphere. The neural substrate for the increased activation and field strength at long latencies during bilateral stimulation can be accounted for in three ways. Under bilateral stimulus conditions, more neurons may be active, neuronal firing rate may increase, and/or neural activity may be more synchronous.

Action Potentials↗

PubMed2000

Organization and connections of V1 in Monodelphis domestica.

We examined the internal organization and connections of the primary visual area, V1, in the South American marsupial Monodelphis domestica. Multiunit electrophysiological recording techniques were used to record from neurons at multiple sites. Receptive field location, size, progressions, and reversals were systematically examined to determine the visuotopic organization of V1 and its boundaries with adjacent visual areas. As in other mammals, a virtually complete representation of the visual hemifield was observed in V1, which was coextensive with a region of dense myelination. The vertical meridian was represented at the rostrolateral boundary of the field, the upper visual quadrant was represented caudolaterally, whereas the lower visual quadrant was represented rostromedially. Injections of fluorescent tracers into V1 revealed dense connections with cortex immediately adjacent to the rostrolateral boundary, in peristriate cortex (PS or V2). Connections were also consistently observed with a caudotemporal area (CT), entorhinal cortex (EC), and multimodal cortex (auditory/visual, A/V). These results demonstrate that M. domestica possess a highly differentiated neocortex with clear functional and architectonic cortical field boundaries, as well as discrete patterns of cortical connections. Some connections of V1 are similar to those observed in eutherian mammals, such as connections with V2 and extrastriate areas (e.g., CT), which suggests that there are general features of visual system organization that all mammals possess due to retention from a common ancestor. On the other hand, connections of V1 with EC and multimodal cortex may be a primitive feature of visual cortex that was lost in some lineages, may be a derived feature of marsupial neocortex, or may be a feature particular to mammals with small brains.

Animals↗

PubMed2000

Somatotopic organization of cortical fields in the lateral sulcus of Homo sapiens: evidence for SII and PV.

The human somatosensory cortex in the Sylvian fissure was examined using functional magnetic resonance imaging to describe the number and internal organization of cortical fields present. Somatic stimuli were applied to the lips, face, hand, trunk, and foot of 18 human subjects. Activity patterns were transposed onto three-dimensional magnetic resonance images of the brain so that the location of activity associated with the different stimuli could be related to specific regions of the cortex. There were several consistent findings. First, there were three regions of activity in the lateral sulcus associated with stimulation of the contralateral body. The most consistent locus of activation was on the upper bank of the lateral sulcus, continuing onto the operculum. The other two areas, one rostral and one caudal to this large central area, were smaller and were activated less consistently. Second, when activity patterns in the large central area resulting from stimulation of all body parts were considered, this region appeared to contain two fields that corresponded in location and somatotopic organization to the second somatosensory area (SII) and the parietal ventral area (PV). Finally, patterns of activation within SII and PV were somewhat variable across subjects. Repeated within-subject stimulus presentation indicated that differences across subjects were not due to inconsistent stimulus presentation. Comparisons with other mammals suggest that some features of organization are found only in primates. It is hypothesized that these features may be associated with manual dexterity and coordination of the hands, a characteristic generally restricted to the primate lineage.

Animals↗

PubMed2000

Multiple somatosensory areas in the anterior parietal cortex of the California ground squirrel (Spermophilus beecheyii).

Multiunit electrophysiological recording techniques were used to explore the somatosensory cortex of the California ground squirrel (Spermophilus beecheyii). Cortex rostral and caudal to the primary somatosensory area (SI) contained neurons that responded to stimulation of deep receptors and to muscle and joint manipulation. The region of cortex rostral to SI was termed the rostral field (R) because of possible homologies with a similar field described in other mammals. Cortex caudal to SI had neurons that responded to stimulation of deep receptors and has been termed the parietal medial area (PM), as in previous investigations in squirrels. Like SI, both R and PM contained a complete or almost complete representation of the body surface, although the receptive field size for clusters of neurons in these regions was somewhat larger than those for clusters of neurons in SI. Electrophysiological recording results were correlated with histologically processed tissue that had been sectioned tangentially. Although SI was clearly identified as a myelin-dense region, both R and PM stained much less densely for myelin. Our results indicate that as in a number of other mammals including monotremes, marsupials, carnivores, and primates, the anterior parietal cortex of the California ground squirrel contains multiple representations of the sensory epithelium. This work, as well as a growing body of studies of somatosensory cortex organization in a variety of mammals, indicates that anterior parietal fields other than SI existed early in mammalian evolution, and were present in the common ancestor of all mammals.

Animals↗

PubMed2000

Arealization of the neocortex in mammals: genetic and epigenetic contributions to the phenotype.

The neocortex is composed of areas that are functionally, anatomically and histochemically distinct. In comparison to most other mammals, humans have an expanded neocortex, with a pronounced increase in the number of cortical areas. This expansion underlies many complex behaviors associated with human capabilities including perception, cognition, language and volitional motor responses. In the following review we consider data from comparative studies as well as from developmental studies to gain insight into the mechanisms involved in arealization, and discuss how these mechanisms may have been modified in different lineages over time to produce the remarkable degree of organizational variability observed in the neocortex of mammals. Because any phenotype is a result of the complex interactions between genotypic influences and environmental factors, we also consider environmental, or epigenetic, contributions to the organization of the neocortex.

Animals↗

PubMed1999

Formation of cortical fields on a reduced cortical sheet.

Theories of both cortical field development and cortical evolution propose that thalamocortical projections play a critical role in the differentiation of cortical fields (; ). In the present study, we examined how changing the size of the immature neocortex before the establishment of thalamocortical connections affects the subsequent development and organization of the adult neocortex. This alteration in cortex is consistent with one of the most profound changes made to the mammalian neocortex throughout evolution: cortical size. Removing the caudal one-third to three-fourths of the cortical neuroepithelial sheet unilaterally at an early stage of development in marsupials resulted in normal spatial relationships between visual, somatosensory, and auditory cortical fields on the remaining cortical sheet. Injections of neuroanatomical tracers into the reduced cortex revealed in an altered distribution of thalamocortical axons; this alteration allowed the maintenance of their original anteroposterior distribution. These results demonstrate the capacity of the cortical neuroepithelium to accommodate different cortical fields at early stages of development, although the anteroposterior and mediolateral relationships between cortical fields appear to be invariant. The shifting of afferents and efferents with cortical reduction or expansion at very early stages of development may have occurred naturally in different lineages over time and may be sufficient to explain much of the phenotypic variation in cortical field number and organization in different mammals.

Aging↗

PubMed1999

The use of fMRI for determining the topographic organization of cortical fields in human and nonhuman primates.

In this study, we demonstrate activation of somatosensory cortex in the anesthetized macaque monkey and awake human using fMRI, and confirm the topographic organization of somatosensory cortex previously described in both species. The macaque model provides an efficient means of addressing questions regarding the capabilities and neurophysiological relevance of fMRI, and serves as an interface between established invasive electrophysiological methods in nonhuman primates, and noninvasive imaging assays of functional activation in humans.

Anesthetics↗

PubMed1999

Organization of somatosensory cortex in three species of marsupials, Dasyurus hallucatus, Dactylopsila trivirgata, and Monodelphis domestica: neural correlates of morphological specializations.

The organization of somatosensory neocortex was investigated in three species of marsupials, the northern quoll (Dasyurus hallucatus), the striped possum (Dactylopsila trivirgata), and the short-tailed opossum (Monodelphis domestica). In these species, multiunit microelectrode mapping techniques were used to determine the detailed organization of the primary somatosensory area (SI). In the striped possum and quoll, the topography of somatosensory regions rostral (R), and caudal (C) to SI were described as well. Lateral to SI, two fields were identified in the striped possum, the second somatosensory area (SII) and the parietal ventral area (PV); in the quoll, there appeared to be only one additional lateral field which we term SII/PV. Visual and auditory cortices adjacent to somatosensory cortex were also explored, but the details of organization of these regions were not ascertained. In these animals, electrophysiological recording results were related to cortical myeloarchitecture and/or cytochrome oxidase staining. In one additional species, the fat-tailed dunnart (Sminthopsis crassicaudata), an architectonic analysis alone was carried out, and compared with the cortical architecture and electrophysiological recording results in the other three species. We discuss our results on the internal organization of SI in relation to the morphological specializations that each animal possesses. In addition, we discuss the differences in the organization of SI, and how evolutionary processes and developmental and adult neocortical plasticity may contribute to the observed variations in SI.

Animals↗

PubMed1998

Interhemispheric connections of somatosensory cortex in the flying fox.

The interhemispheric connections of somatosensory cortex in the gray-headed flying fox (Pteropus poliocephalus) were examined. Injections of anatomical tracers were placed into five electrophysiologically identified somatosensory areas: the primary somatosensory area (SI or area 3b), the anterior parietal areas 3a and 1/2, and the lateral somatosensory areas SII (the secondary somatosensory area) and PV (pairetal ventral area). In two animals, the hemisphere opposite to that containing the injection sites was explored electrophysiologically to allow the details of the topography of interconnections to be assessed. Examination of the areal distribution of labeled cell bodies and/or axon terminals in cortex sectioned tangential to the pial surface revealed several consistent findings. First, the density of connections varied as a function of the body part representation injected. For example, the area 3b representation of the trunk and structures of the face are more densely interconnected than the representation of distal body parts (e.g., digit 1, D1). Second, callosal connections appear to be both matched and mismatched to the body part representations injected in the opposite hemisphere. For example, an injection of retrograde tracer into the trunk representation of area 3b revealed connections from the trunk representation in the opposite hemisphere, as well as from shoulder and forelimb/wing representations. Third, the same body part is differentially connected in different fields via the corpus callosum. For example, the D1 representation in area 3b in one hemisphere had no connections with the area 3b D1 representation in the opposite hemisphere, whereas the D1 representation in area 1/2 had relatively dense reciprocal connections with area 1/2 in the opposite hemisphere. Finally, there are callosal projections to fields other than the homotopic, contralateral field. For example, the D1 representation in area 1/2 projects to contralateral area 1/2, and also to area 3b and SII.

Animals↗

PubMed1998

What can monotremes tell us about brain evolution?

The present review outlines studies of electrophsyiological organization, cortical architecture and thalmocortical and corticocortical connections in monotremes. Results of these studies indicate that the neocortex of monotremes has many features in common with other mammals. In particular, monotremes have at least two, and in some instances three, sensory fields for each modality, as well as regions of bimodal cortex. The internal organization of cortical fields and thalamocortical projection patterns are also similar to those described for other mammals. However, unlike most mammals investigated, the monotreme neocortex has cortical connections between primary sensory fields, such as SI and VI. The results of this analysis lead us to pose the question of what monotremes can tell us about brain evolution. Monotremes alone can tell us very little about the evolutionary process, or the construction of complex neural networks, as an individual species represents only a single example of what the process is capable of generating. Perhaps a better question is: what can comparative studies tell us about brain evolution? Monotreme brains, when compared with the brains of other animals, can provide some answers to questions about the evolution of the neocortex, the historical precedence of some features over others, and how basic circuits were modified in different lineages. This, in turn, allows us to appreciate how normal circuits function, and to pose very specific questions regarding the development of the neocortex.

Animals↗

PubMed1998

Modular subdivisions of dolphin insular cortex: does evolutionary history repeat itself?

The structural organization of the insular cortex in the bottlenose dolphin was investigated by examining Nissl- and myelin-stained tissue that was sectioned coronally and tangentially. An uneven distribution of cell clusters that coincided with myelin-light zones was observed in layer II. When the present observations were compared to descriptions of modules in other animals, we found that the range of module size is restricted, while the size of the brain, particularly the neocortex, varies dramatically. Indeed, despite the tremendous expansion of the cetacean neocortex, the size of the modules in the insular cortex is similar to that described for small-brained mammals like the mouse, suggesting that module size is evolutionarily stable across species. Selection for optimal-size processing units, in terms of the lengths of connections within and between them, is a likely source of this stability.

Animals↗

PubMed1997

Organization of sensory cortex in a Madagascan insectivore, the tenrec (Echinops telfairi).

We identified subdivisions of somatosensory cortex, and the borders and extents of auditory and visual cortex in Madagascan tenrecs (Echinops telfairi) by using microelectrode recording techniques and cortical myeloarchitecture. There was evidence for three distinct somatosensory fields. The primary somatosensory area (S1) contained an orderly representation of the contralateral body surface that stained darkly for myelin. Neurons were activated by light touch, and receptive fields were often small, especially for the snout. Immediately rostral to S1, a lightly myelinated rostral field (R) also contained a representation of the contralateral body, although the internal topography was not fully determined. Neurons in R responded to manipulations of body parts and tissue displacements. A small, moderately myelinated area lateral to S1 was termed PV/S2 because it possessed features that were similar to both the parietal ventral area (PV) and the second somatosensory area (S2) in other mammals. Neurons in PV/S2 responded to light tactile stimulation. A densely myelinated oval of cortex caudal to PV/S2, the auditory area (A), contained neurons that responded to clicks, and the densely myelinated caudomedial visual area (V) contained neurons that were activated by stimulation of one or both eyes. Some characteristics of V were similar to the primary visual area (V1) described in other mammals. A visual area located in rostromedial cortex (RV) contained neurons that were highly responsive to visual stimulation. Area RV may be a specialization of tenrecs or an elaboration of a visuomotor field that has been retained in most extant mammals. The results support the view that most of the neocortex of primitive mammals was composed of a few sensory areas. J. Comp. Neurol. 379:399-414, 1997.

Animals↗

PubMed1995

Organization of somatosensory cortex in monotremes: in search of the prototypical plan.

The present investigation was designed to determine the number and internal organization of somatosensory fields in monotremes. Microelectrode mapping methods were used in conjunction with cytochrome oxidase and myelin staining to reveal subdivisions and topography of somatosensory cortex in the platypus and the short-billed echidna. The neocortices of both monotremes were found to contain four representations of the body surface. A large area that contained neurons predominantly responsive to cutaneous stimulation of the contralateral body surface was identified as the primary somatosensory area (SI). Although the overall organization of SI was similar in both mammals, the platypus had a relatively larger representation of the bill. Furthermore, some of the neurons in the bill representation of SI were also responsive to low amplitude electrical stimulation. These neurons were spatially segregated from neurons responsive to pure mechanosensory stimulation. Another somatosensory field (R) was identified immediately rostral to SI. The topographic organization of R was similar to that found in SI; however, neurons in R responded most often to light pressure and taps to peripheral body parts. Neurons in cortex rostral to R were responsive to manipulation of joints and hard taps to the body. We termed this field the manipulation field (M). The mediolateral sequence of representation in M was similar to that of both SI and R, but was topographically less precise. Another somatosensory field, caudal to SI, was adjacent to SI laterally at the representation of the face, but medially was separated from SI by auditory cortex. Its position relative to SI and auditory cortex, and its topographic organization led us to hypothesize that this caudal field may be homologous to the parietal ventral area (PV) as described in other mammals. The evidence for the existence of four separate representations in somatosensory cortex in the two species of monotremes indicates that cortical organization is more complex in these mammals than was previously thought. Because the two monotreme families have been separate for at least 55 million years (Richardson, B.J. [1987] Aust. Mammal. 11:71-73), the present results suggest either that the original differentiation of fields occurred very early in mammalian evolution or that the potential for differentiation of somatosensory cortex into multiple fields is highly constrained in evolution, so that both species arrived at the same solution independently.

Animals↗

PubMed1995

The organization of neocortex in mammals: are species differences really so different?

By examining a variety of mammals, it is possible to determine common features of cortical organization, and from these infer homologies across species. Such analysis also enables differences in the organization of the neocortex to be identified. Species differ in the amount of cortex that is devoted to a particular sensory system, in the size and configuration of a cortical field, in the number of cortical fields, and in the pattern of connections of homologous fields. It is suggested that the plan of organization that is retained is the result of homologous developmental events, and that modifications to this plan are generated by a limited set of mechanisms. These types of changes to the common network might account for the sensory and behavioural diversity that is observed in extant mammals.

Animals↗