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Homotopic and heteropic callosal afferents of caudal inferior parietal lobule in Macaca mulatta
Abstract
We have examined callosal-axon neurons giving rise to homotopic and heterotopic callosal projections to caudal inferior parietal lobule (area PG) in Macaca mulatta, identifying these neurons by means of retrograde axonal transport of horseradish peroxidase. The labeled neurons in the homotopic region occur predominantly in layers IIIB and V. A moderate number are seen also in layer VI, a smaller number in layer IV, and rare cells occur in layer II. These neurons occupy a region very similar in outline to the injection area, and though variable in density in the horizontal plane are continuously distributed in this plane.
The heterotopic neurons are seen in the contralateral cingulate gyrus, continuing caudally into medial parietal cortex, in the cortex of the superior temporal and occipitotemporal sulci, in the caudal superior temporal gyrus, and in the caudal inferior parietal lobule, behind the homotopic area. These same regions on the ipsilateral side contain labeled neurons of origin of ipsilateral association projections to area PG. For other ipsilateral association regions (e.g., frontal lobe), no corresponding contralateral heterotopic labeling was found. A review of the literature on heterotopic callosal connections allows tentative generalization of this conclusion: The callosal heterotopic connections of a particular cortical area are made with regions which on the ipsilateral side have association connections with that area, though usually not with all of such regions.
... Commissural connections are more likely homotopic than heterotopic, that is, they have more projections connecting bilateral homologous areas rather than non-homologous regions (Raybaud, 2010). This is particularly evident in the CC (Hedreen and Yin, 1981;Jarbo et al., 2012), which can be segmented into different portions serving as commissural pathways for the cortical lobes ( Fig. 2) (Abe et al., 2004;Hofer et al., 2008;Hofer and Frahm, 2006). Heterotopic connections link a specific brain region with different areas of the opposite hemisphere, which are a subset of the contralateral counterpart of ipsilateral associative connections of that region (Hedreen and Yin, 1981). ...
... This is particularly evident in the CC (Hedreen and Yin, 1981;Jarbo et al., 2012), which can be segmented into different portions serving as commissural pathways for the cortical lobes ( Fig. 2) (Abe et al., 2004;Hofer et al., 2008;Hofer and Frahm, 2006). Heterotopic connections link a specific brain region with different areas of the opposite hemisphere, which are a subset of the contralateral counterpart of ipsilateral associative connections of that region (Hedreen and Yin, 1981). In other words, if an area such as the left dorsolateral prefrontal cortex is connected with the left parietal cortex, it might also be connected with the right parietal cortex (for an illustration of this concept, see Fig. 2, top panel). ...
In the absence of the corpus callosum due to either surgical transection or congenital agenesis, the interhemispheric exchange of information is disrupted, as emphasized by several clinical studies. In such cases, a reduction of interhemispheric functional connectivity, that is, an increased independence of the functional signals of the two disconnected hemispheres, is expected to occur. A growing literature has investigated this hypothesis, and a number of studies were able to confirm it. However, this increased independence is not always observed, especially in congenital agenesis, in which the functional signals of the two hemispheres are often found to be characterized by synchronization or correlation. The extent of these counterintuitive findings and possible explanations are discussed. Overall, these findings highlight both methodological and theoretical considerations that emphasize the importance of subcortical structures, the preservation of which may underlie alternative pathways of functional connectivity and interhemispheric communication.
... Only a minority of the neurons affected are likely to have had projections to the neostriatum, as corticostriatal neurons are located principally in the upper portion of layer V [13,16,17]. Neurons in layer V constitute the principal source of projections to subcortical regions and also project to other regions of cerebral cortex [14,16]. Neurons in layer VI project predominantly to the thalamus, the claustrum, and other regions of cerebral cortex [4,14,16,21,25]. ...
... Neurons in layer V constitute the principal source of projections to subcortical regions and also project to other regions of cerebral cortex [14,16]. Neurons in layer VI project predominantly to the thalamus, the claustrum, and other regions of cerebral cortex [4,14,16,21,25]. Thus it is unlikely that neurons in layer VI were lost as a result of retrograde degeneration secondary to striatal pathology. ...
Neuronal loss in the cerebral cortex in Huntington's disease (HD) has not been well documented, nor has its laminar pattern been definitively established. We therefore counted neurons in individual cortical laminae in the dorsal frontal cortex of 5 HD and 5 control autopsy brains. Significant neuronal loss (to 57% of control, P = 0.002) was found in layer VI of HD brains. These cells project principally to the thalamus, the claustrum and other regions of cerebral cortex; thus their loss is unlikely to be the result of retrograde degeneration secondary to striatal pathology. Layer V neurons were also decreased (to 71% of control, P = 0.034). Degeneration of cerebral cortical neurons may be at least partly responsible for some of the non-choreic symptoms of HD, such as dementia, irritability, apathy, and depression.
... Although Hedreen and Yin (1981) reported that callosal connections are less dense between hetero-than homotopic sites, Kennedy et al. (1991) suggested that this may result from the fact that heterotopy entails a divergence of connectivity of callosal fibers from source to recipient cortex. Thus, there may be as many hetero-as homotopic fibers, but, because of divergence, the former are lower in density. ...
Research on the anatomical bases of interhemispheric interaction, including individual differences in corpus callosum (CC) anatomy, is reviewed. These anatomical findings form the basis for the discussion of two major themes. The first considers interhemispheric transfer time (IHTT) and related issues. These include varieties of IHTT and possible directional asymmetries of IHTT. Evidence suggests that pathological variations in IHTT may have cognitive consequences. The second involves conditions under which interhemispheric interaction is necessary and beneficial. The data suggest that when both hemispheres have some competence at a difficult task, there is a benefit to interhemispheric interaction. The role of the CC in the dynamic distribution of attention may be particularly relevant to this advantage. Throughout the article reference is made to individual differences and developmental changes associated with interhemispheric interaction.
... There is a vast literature of observations on cerebral connections that precede the DTI era. This literature addresses ipsilateral cortico-cortical [10,11,14,57,[97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114], commissural (e.g., callosal) (e.g., [45,[115][116][117][118][119]), corticothalamic (e.g., [120][121][122]), corticostriatal (e.g., [123,124,125,126,127,128,129,130,131,132]), cortico-amygdaloid (e.g., [133,134,135,136]), and cortico-hippocampal connectivity (e.g., [137,138,139,140,141,142,143,144,145]), as well as corticopontine pathways (e.g., [146,147,148,149,150,151,152,153,154]). For the cortico-cortical fiber tracts in particular, connectional relationships are inferred principally from the topographic characteristics of the fiber systems with regions of interest as collated by traditional pre-DTI neuroanatomists (e.g., [10,11,57,108]). ...
A complete structural definition of the human nervous system must include delineation of its wiring diagram (e.g., [1]). The complete formulation of the human brain circuit diagram (BCD; [2]) has been hampered by an inability to determine connections in their entirety (i.e., not only pathway stems, but also origins and terminations). From a structural point of view, a neuroanatomic formulation of the BCD should include the origins and terminations of each fiber tract as well as the topographic course of the fiber tract in three dimensions. Classic neuroanatomical studies have provided trajectory information for pathway stems and their speculative origins and terminations [3–7]. We have summarized these studies previously [7] and present them here in a macroscale-level human cerebral structural connectivity matrix. A matrix in the present context is an organizational construct that embodies anatomical knowledge about cortical areas and their connections. This is represented in relation to parcellation units according to the Harvard-Oxford Atlas neuroanatomical framework established by the Center for Morphometric Analysis at Massachusetts General Hospital in the early 2000s, which is based on the MRI volumetrics paradigm of Dr. Verne Caviness and colleagues [8]. This is a classic connectional matrix based mainly on data predating the advent of DTI tractography, which we refer to as the "pre-DTI era" human structural connectivity matrix. In addition, we present representative examples that incorporate validated structural connectivity information from non-human primates and more recent information on human structural connectivity emerging from DTI tractography studies. We refer to this as the "DTI era" human structural connectivity matrix. This newer matrix represents a work in progress and is necessarily incomplete due to the lack of validated human connectivity findings on origins and terminations as well as pathway stems. Importantly, we use a neuroanatomical typology to characterize different types of connections in the human brain, which is critical for organizing the matrices and the prospective database. Although substantial in detail, the present matrices may be assumed to be only partially complete because the sources of data relating to human fiber system organization are limited largely to inferences from gross dissections of anatomic specimens or extrapolations of pathway tracing information from non-human primate experiments [2,9,10]. These matrices, which embody a systematic description of cerebral connectivity, can be used in cognitive and clinical studies in neuroscience and, importantly, to guide research efforts for further elucidating, validating and completing the human brain circuit diagram [2].
... In NHP parietal areas have dense callosal connections, which are both homotopic (i.e., between left-right equivalent subdivisions) and heterotopic (Fig. 2). The heterotopic connections, although less dense, are to the same areas that receive ipsilateral PPC connections, including the rhinal and calcarine sulci (Hedreen and Yin 1981;Cavada and Goldman-Rakic 1989b; and for PFC: Barbas et al. 2005). Thus, pyramidal neurons have 1) intrinsic horizontal collaterals (see below), 2) branches to a set of ipsilateral cortical areas, and 3) branches to homotopic and heterotopic contralateral areas (the latter, with fewer synapses). ...
... In NHP parietal areas have dense callosal connections, which are both homotopic (i.e., between left-right equivalent subdivisions) and heterotopic (Fig. 2). The heterotopic connections, although less dense, are to the same areas that receive ipsilateral PPC connections, including the rhinal and calcarine sulci (Hedreen and Yin 1981;Cavada and Goldman-Rakic 1989b; and for PFC: Barbas et al. 2005). Thus, pyramidal neurons have 1) intrinsic horizontal collaterals (see below), 2) branches to a set of ipsilateral cortical areas, and 3) branches to homotopic and heterotopic contralateral areas (the latter, with fewer synapses). ...
The angular gyrus is associated with a spectrum of higher order cognitive functions. This mini-review undertakes a broad survey of putative neuroanatomical substrates, guided by the premise that area-specific specializations derive from a combination of extrinsic connections and intrinsic area properties. Three levels of spatial resolution are discussed: cellular, supracellular connectivity, and synaptic micro-scale, with examples necessarily drawn mainly from experimental work with nonhuman primates. A significant factor in the functional specialization of the human parietal cortex is the pronounced enlargement. In addition to "more" cells, synapses, and connections, however, the heterogeneity itself can be considered an important property. Multiple anatomical features support the idea of overlapping and temporally dynamic membership in several brain wide subnetworks, but how these features operate in the context of higher cognitive functions remains for continued investigations.
... Consistent with previous EM-fMRI studies (Sultan et al., 2011;Tolias et al., 2005), the ipsilateral cortical connections excluded areas known to be polysynaptically connected with LPFC, such as the primary visual cortex. Consistent with tracing studies (Cavada and Goldman-Rakic, 1989;Hedreen and Yin, 1981;Innocenti, 1986), the contralateral cortical connections of LPFC were much more confined than the ipsilateral connections, mostly found in LPFC areas homotopic as well as heterotopic to the stimulation sites, and areas in medial prefrontal and orbitofrontal cortices (Figures 1E and 1F). This paper focuses on the ipsilateral cortical connections. ...
The lateral prefrontal cortex (LPFC) of primates plays an important role in executive control, but how it interacts with the rest of the cortex remains unclear. To address this, we densely mapped the cortical connectome of LPFC, using electrical microstimulation combined with functional MRI (EM-fMRI). We found isomorphic mappings between LPFC and five major processing domains composing most of the cerebral cortex except early sensory and motor areas. An LPFC grid of ∼200 stimulation sites topographically mapped to separate grids of activation sites in the five domains, coarsely resembling how the visual cortex maps the retina. The temporal and parietal maps largely overlapped in LPFC, suggesting topographically organized convergence of the ventral and dorsal streams, and the other maps overlapped at least partially. Thus, the LPFC contains overlapping, millimeter-scale maps that mirror the organization of major cortical processing domains, supporting LPFC’s role in coordinating activity within and across these domains.
... At first glance these results do not fit to the well-established belief that callosal axons mainly connect homotopic cortices (Schmahmann and Pandya 2006). However, heterotopic transcallosal projections exist (Chovsepian et al. 2017;Hedreen and Yin 1981;Mancuso, Costa, et al. 2019a, b), especially in partial ACC. Wahl et al. (2009) investigated interhemispheric white matter connectivity in parietal ACC and identified not only homotopic but also heterotopic connections in the majority of their patients. ...
The present study is interested in the role of the corpus callosum in the development of the language network. We, therefore, investigated language abilities and the language network using task-based fMRI in three cases of complete agenesis of the corpus callosum (ACC), three cases of partial ACC and six controls. Although the children with complete ACC revealed impaired functions in specific language domains, no child with partial ACC showed a test score below average. As a group, ACC children performed significantly worse than healthy controls in verbal fluency and naming. Furthermore, whole-brain ROI-to-ROI connectivity analyses revealed reduced intrahemispheric and right intrahemispheric functional connectivity in ACC patients as compared to controls. In addition, stronger functional connectivity between left and right temporal areas was associated with better language abilities in the ACC group. In healthy controls, no association between language abilities and connectivity was found. Our results show that ACC is associated not only with less interhemispheric, but also with less right intrahemispheric language network connectivity in line with reduced verbal abilities. The present study, thus, supports the excitatory role of the corpus callosum in functional language network connectivity and language abilities.
... Unlike the dPul stimulation effects in the opposite hemisphere, the activation of heterotopic regions in the opposite parietal and parieto-temporal cortex by the LIP stimulation cannot be taken as a definitive proof of polysynaptic propagation, due to a presence of heterotopic transcallosal connections between these regions (Hedreen and Yin, 1981). It remains to be investigated if these connections are dense enough to support monosynaptic transcallosal activation, as an alternative to the polysynaptic transmission via homotopic LIP. ...
The thalamic pulvinar and the lateral intraparietal area (LIP) share reciprocal anatomical connections and are part of an extensive cortical and subcortical network involved in spatial attention and oculomotor processing. The goal of this study was to compare the effective connectivity of dorsal pulvinar (dPul) and LIP and to probe the dependency of microstimulation effects on task demands and spatial tuning properties of a given brain region. To this end, we applied unilateral electrical microstimulation in the dPul and LIP in combination with event-related BOLD fMRI in monkeys performing fixation and memory-guided saccade tasks. Microstimulation in both dPul and LIP enhanced task-related activity in monosynaptically-connected prefrontal cortex and along the superior temporal sulcus (STS) as well as in extrastriate cortex. Both dPul and LIP stimulation also elicited activity in several cortical areas in the opposite hemisphere, implying polysynaptic propagation of excitation. LIP microstimulation elicited strong activity in the opposite homotopic LIP while no homotopic activation was found during dPul stimulation. Despite extensive activation along the intraparietal sulcus evoked by LIP stimulation, there was a difference in frontal and occipital connectivity elicited by posterior and anterior LIP stimulation sites. Comparison of dPul stimulation with the adjacent but functionally distinct ventral pulvinar also showed distinct connectivity. On the level of single trial timecourses within a region, most microstimulation regions did not show task-dependence of stimulation-elicited response modulation. Across regions, however, there was an interaction between the task and the stimulation, and task-specific correlations between the initial spatial selectivity and the magnitude of stimulation effect were observed. Consequently, stimulation-elicited modulation of task-related activity was best fitted by an additive model scaled down by the initial response amplitude. In summary, we identified overlapping and distinct patterns of thalamocortical and corticocortical connectivity of the two key visuospatial areas, highlighting the dorsal bank and fundus of STS as a prominent node of shared circuitry. Spatial task-specific and partly polysynaptic modulations of cue and saccade planning delay period activity in both hemispheres exerted by unilateral pulvinar and parietal stimulation provide insight into the distributed interhemispheric processing underlying spatial behavior.
Highlights
Electrical stimulation of pulvinar and LIP was used to study fMRI effective connectivity
Both regions activated prefrontal cortex and the dorsal bank of superior temporal sulcus
Activations within and across hemispheres suggest polysynaptic propagation
Stimulation effects show interactions between task- and spatial selectivity
Stimulation effects are best fitted by an additive model scaled by the initial response
... However, in addition to the homotopic structural connections through the CC, there is a sizeable fraction of heterotopic transcallosal projections (Chovsepian, Empl, Correa, & Bareyre, 2017). These are a subset of the contralateral counterpart of ipsilateral associative connections (Hedreen & Yin, 1981;Mancuso, Uddin, Nani, Costa, & Cauda, 2019). However, above all, the relationship between structure and function is not straightforward (Damoiseaux & Greicius, 2009;Mancuso, Uddin, et al., 2019). ...
The specific role of the corpus callosum in language network organization is unclear, two contrasting models have been proposed: inhibition of homotopic areas allowing for independent functioning of the hemispheres versus integration of information from both hemispheres. The present study aimed to add to this discussion with the first investigation of language network connectivity in combination with corpus callosum volume measures. In 38 healthy children aged 6‐12, we performed task‐based functional magnetic resonance imaging to measure language network connectivity, used structural magnetic resonance imaging to quantify corpus callosum subsection volumes, and administered various language tests to examine language abilities. We found an increase of left intrahemispheric and bilateral language network connectivity and a decrease of right intrahemispheric connectivity associated with larger volumes of the posterior, mid‐posterior, and central subsections of the corpus callosum. Consistent with that, larger volumes of the posterior parts of the corpus callosum were significantly associated with better verbal fluency and vocabulary, the anterior corpus callosum volume was positively correlated with verbal span. Thus, children with larger volumes of CC subsections showed increased interhemispheric language network connectivity and were better in different language domains. The present study presents the first evidence that the corpus callosum is directly linked to language network connectivity and underlines the excitatory role of the corpus callosum in the integration of information from both hemispheres.
... Animal studies have shown that callosal axons originate from a diverse population of neocortical pyramidal neurons whose cell bodies reside in cortical layers II/III (approximately 80% in rodents), layer V (approximately 20% in rodents) and, to a lesser extent, layer VI Koester & O'Leary, 1994;Rash & Richards, 2001;Richards et al. 2004;Lindwall et al. 2007;Donahoo & Richards, 2009;Fame et al. 2011;Leyva-Diaz & Lopez-Bendito, 2013). Anatomical studies in primates, including humans, have shown that the majority of callosal axons originate from pyramidal neurons, mostly from layer III pyramidal neurons that connect contralateral homotypic areas, and, to a lesser extent, heterotypic cortices, and finally, a small proportion of callosal axons arise form migrating neurons during development (Hedreen & Yin, 1981;Schmahmann & Pandya, 2006;Wahl et al. 2007). Diffusion tensor tractography imaging (DTI) studies have shown that the callosal axons are topographically organized along the anteroposterior axis and homotopically link contralateral cortical regions in the Rhesus monkey (Hofer et al. 2008) and in healthy humans (Hofer & Frahm, 2006;Huang et al. 2009), and heterotopically, in patients with partial callosal agenesis (Wahl et al. 2009). ...
The early development and growth of the corpus callosum are supported by several midline transient structures in mammals that include callosal septa (CS), which are present only in the second half of gestation in humans. Here we provide new data that support the guidance role of CS in corpus callosum development, derived from the analysis of 46 postmortem fetal brains, ranging in age from 16 to 40 post conception weeks (PCW). Using immunohistochemical methods, we show the expression pattern of guidance cues ephrinA4 and neogenin, extracellular protein fibronectin, as well as non‐activated microglia in the CS. We found that the dynamic changes in expression of guidance cues, cellular and extracellular matrix constituents in the CS correlate well with the growth course of the corpus callosum at midsagittal level. The CS reach and maintain their developmental maximum between 20 and 26 PCW and can be visualized as hypointense structures in the ventral callosal portion with ex vivo (in vitro) T2‐weighted 3T magnetic resonance imaging (MRI). The maximum of septal development overlaps with an increase in the callosal midsagittal area, whereas the slow, gradual resolution of CS coincides with a plateau of midsagittal callosal growth. The recognition of CS existence in human fetal brain and the ability to visualize them by ex vivoMRI attributes a potential diagnostic value to these transient structures, as advancement in imaging technologies will likely also enable in vivoMRI visualization of the CS in the near future.
... FC appears to be intimately related to structural HC [35][36][37][38][39][40] , the greater part of which is mediated by many fibers of the corpus callosum (CC) [41][42][43][44][45][46] . In fact, interhemispheric FC and EEG coherence have been found to be reduced www.nature.com/scientificreports ...
Homotopic connectivity (HC) is the connectivity between mirror areas of the brain hemispheres. It can exhibit a marked and functionally relevant spatial variability, and can be perturbed by several pathological conditions. the voxel-mirrored homotopic connectivity (VMHC) is a technique devised to enquire this pattern of brain organization, based on resting state functional connectivity. since functional connectivity can be revealed also in a meta-analytical fashion using co-activations, here we propose to calculate the meta-analytic homotopic connectivity (MHC) as the meta-analytic counterpart of the VMHC. the comparison between the two techniques reveals their general similarity, but also highlights regional differences associated with how HC varies from task to rest. Two main differences were found from rest to task: (i) regions known to be characterized by global hubness are more similar than regions displaying local hubness; and (ii) medial areas are characterized by a higher degree of homotopic connectivity, while lateral areas appear to decrease their degree of homotopic connectivity during task performance. These findings show that MHC can be an insightful tool to study how the hemispheres functionally interact during task and rest conditions
... Figure 2.23: adapted from a paper by J. R. Wolff and L Zaborsky (1979) in I. S. Russell et al. (eds), Structure and Function of Cerebral Commissures, New York, Macmillan. Figure 3.1: from a paper by P. S. Goldman-Rakic (1984) Trends in the Neurosciences, Nov., 419-24* Figures 3.2 and 3.4: from a paper by J. C. Hedreen and T. C. T. Yin (1981) Journal of Comparative Neurology,197,.3: adapted from a paper by P. Rakic and P. I. Yakovlev (1968) Journal of Comparative Neurology, 132, 45-72. ...
... Callosal connections have been frequently reported to be heterotopic meaning that contralateral projections mirror the extended ipsilateral projections-also in other areas than only the homotopically corresponding one-on the same level of hierarchy, but at lower density (e.g., in monkeys: Hedreen and Yin, 1981;Barbas et al., 2005). ...
Anatomy and function of long-range intrinsic and callosal axons in primary visual cortex are reviewed. In cats, both arborize in a patchy manner, in an orderly relationship to the visuotopic map and visual stimulus features. Patches tend to link neurons with similar contour and direction preference aligned along a collinear visual field axis. Direct investigation of callosal action on visual responses reveals a multiplicative shift without changing neuronal selectivity. Both gain and bias toward excitation or inhibition depend on global stimulus attributes. Interactions are more pronounced for neurons processing similar, in particular cardinal, visual features. As feature selectivity emerges already in ongoing neuronal activity, it is hypothesized that perceptual grouping is anticipated via the feature bias in patchy connections. By comparing data from lateral and feedback circuits, we conclude that visual callosal connections are more similar to intrinsic connections and can be interpreted as extending this circuit across the hemispheres.
... An extreme example of this pertains to the robust interhemispheric projections from visual cortical areas to contralateral speech centers in the dominant hemisphere (Di Virgilio and Clarke 1997). Akin to this, regions of the intraparietal sulcus and inferior-superior convexities make connections with heterotopic areas of the parietal and frontal lobes in the opposite hemisphere (Matsumura and Kubota 1979, Hedreen and Yin 1981, Caminiti and Sbriccoli 1985, Jarbo et al. 2012. It is therefore plausible that there exists an underlying anatomical architecture fostering interhemispheric modulation from the parietal to the motor cortex. ...
Mirror visual feedback (MVF) is potentially a powerful tool to facilitate recovery of disordered movement and stimulate activation of under-active brain areas due to stroke. The neural mechanisms underlying MVF have therefore been a focus of recent inquiry. Although it is known that sensorimotor areas can be activated via mirror feedback, the network interactions driving this effect remain unknown. The aim of the current study was to fill this gap by using dynamic causal modeling to test the interactions between regions in the frontal and parietal lobes that may be important for modulating the activation of the ipsilesional motor cortex during mirror visual feedback of unaffected hand movement in stroke patients. Our intent was to distinguish between two theoretical neural mechanisms that might mediate ipsilateral activation in response to mirror-feedback: transfer of information between bilateral motor cortices versus recruitment of regions comprising an action observation network which in turn modulate the motor cortex. In an event-related fMRI design, fourteen chronic stroke subjects performed goal-directed finger flexion movements with their unaffected hand while observing real-time visual feedback of the corresponding (veridical) or opposite (mirror) hand in virtual reality. Among 30 plausible network models that were tested, the winning model revealed significant mirror feedback-based modulation of the ipsilesional motor cortex arising from the contralesional parietal cortex, in a region along the rostral extent of the intraparietal sulcus. No winning model was identified for the veridical feedback condition. We discuss our findings in the context of supporting the latter hypothesis, that mirror feedback-based activation of motor cortex may be attributed to engagement of a contralateral (contralesional) action observation network. These findings may have important implications for identifying putative cortical areas, which may be targeted with non-invasive brain stimulation as a means of potentiating the effects of mirror training.
... Most callosal fibres connect homologous regions of the two hemispheres (homotopic fibres), although there also are connections between non-homologous areas (heterotopic fibres). The callosal heterotopic connections of a particular cortical area are made with regions which on the ipsilateral side have associated connections with that area, though usually not with all of such regions (Hedreen and Yin, 1981). ...
Ungefähr 95% der männlichen Rechtshänder haben eine linkshemisphärische Spezialisierung für Sprache. Im Gegensatz hierzu sind Ergebnisse der sprachlichen Organisation bei Frauen nicht eindeutig. Es wird angenommen dass diese Vielfalt mit Konzentrationsveränderungen der gonadalen Steroidhormone während des Menstruationszyklus assoziiert sei. In der vorliegenden Arbeit wurde bei männlichen Probanden mittels lateralisierte Darbietung von linguistischen Stimuli während einer funktioneller Magnet Resonanz Tomographie Aufnahme wurde die Organisation und Kapazität der Sprachverarbeitung in der einzelnen Hemisphären erfasst in Männer. In einem weiteren Schritt wurde die gleiche Untersuchung an weiblichen Probanden an zwei Zeitpunkten des Zyklus durchgeführt.
... Given that interhemispheric homotopic areas are typically strongly interacting (Christova et al. 2011) and anatomically interconnected (Hedreen and Yin 1981), we propose that the correlated activity between right temporal pole and left pallidum could be accounted for by the following route: right temporal pole ↔ left temporal pole → left pallidum. This idea needs to be further investigated. ...
Successful diagnosis of PTSD has been achieved using neural correlations from prewhitened magnetoencephalographic (MEG) time series (Georgopoulos et al. in J Neural Eng 7:16011, 2010. doi:10.1088/1741-2560/7/1/016011; James et al. 2015). Here, we show that highly successful classification of PTSD and control subjects can be obtained using neural correlations from prewhitened resting-state fMRI data. All but one PTSD (14/15; sensitivity = 93.3 %) and all but one control (20/21; specificity = 95.2 %) subjects were correctly classified using 15 out of 2701 possible correlations between 74 brain areas. In contrast, correlations of the same but non-prewhitened data yielded chance-level classifications. We conclude that, if properly processed, fMRI has the prospect of aiding significantly in PTSD diagnosis. Twenty-five brain areas were most prominently involved in correct subject classification, including areas from all cortical lobes and the left pallidum.
... A CD signal impinges on LIPpre in one hemisphere, which leads to a transfer of visual information to LIPpost in the other hemisphere. Our observations that across-hemifield remapping is compromised in split-brain monkeys supports the idea that normally the transfer of visual signals relies on the forebrain commissures that link up the entire rostrocaudal extent of the cortex (Pandya and Vignolo, 1969;Seltzer and Pandya, 1983;Schwartz and Goldman-Rakic, 1984;Hedreen and Yin, 1981). Thus, in the most parsimonious circuit, the transfer of visual signals in across-hemifield remapping occurs via the forebrain commissures. ...
... bution. Overall, the patterns are suggestive of different response ʺmodesʺ for motor output, which may include corticospinal efference from multiple regions of motor cortex whose activation time course and motor output efficacy differ. This possibility was explored by comparing waveforms derived from differ‐ ent central regions with the EMG traces. Hedreen & Yin, 1981; Di Virgilio & Clarke, 1997); or (3) heterotopic right frontal‐to‐left central connections, since right frontal responses in this condition begin as early as 50 ms (see general view of callosal connectivity in H. Kennedy et al., 1991). The SMA waveforms are the difference between two foci located at FC2 and Cz because the SCD maps showed ...
The folk belief that the left brain hemisphere is dominant for language and the right for visuospatial functions is incomplete and even misleading. Research shows that asymmetries exist at all levels of the nervous system and apply to emotional as well as to higher cognitive processes. Going beyond the authors' previous book, Brain Asymmetry, this book reflects the most recent thinking on functional asymmetries and their structural correlates in brain anatomy. It emphasizes research using new neuroimaging and neurostimulation techniques such as magnetic resonance imaging (MRI and fMRI), positron emission tomography (PET), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). It also considers clinical applications of asymmetry research. The book contains sections on animal models and basic functions, neuroimaging and brain stimulation studies, visual laterality, auditory laterality, emotional laterality, neurological disorders, and psychiatric disorders.
Bradford Books imprint
... There is also evidence that among the cells of origin of a given projection a certain amount of heterogeneity in their morphology and laminar distribution can exist. This heterogeneity is particularly noticeable in corticocortical projections which can arise from various subtypes of pyramidal cells in layers 2-6, from spiny stellate cells in low layer 3 and layer 4, and from polymorphic cells in lnfragranular layers (Innocenti and Fiore, 1976;Meyer and Albus, 1981; Hedreen and Yin, 1981;Tigges et al., 1981;Lund, 1984;Schwartz and Goldman-Rakic, 1984; Winguth and Winer, 1986; Voigt et al., Einstein and Fitzpatrick, 1991). It is conceivable that the functional properties of the different anatomical types of corticocortical cells are distinct. ...
Herein we describe the inverted cells [defined as those projection neurons having a major dendritic shaft abpially oriented (Bueno-López et al., Eur. J. Neurosci., 3, 415, 1991)] originating a unique set of cortical connections characterized by extraordinarily widespread horizontal distribution. Single and multiple injections of wheatgerm agglutinin - horseradish peroxidase were made in areas 17 and 18 and the resulting retrograde labelling in the cortex was analysed. The findings were assessed in independent control experiments in which Fluoro-Gold was used as retrograde tracer. Following single injections in area 17 several separate patches of labelled cells comprising layers 2–6 were consistently found in area 18. In addition to these associational cells a number of labelled cells appeared at the layer 5/6 border but were distributed over most of the tangential extent of the visual occipital cortex. This widespread pattern was particularly striking in brains after multiple injections. In these brains a conspicuous band of labelled cells at the 5/6 border radiated from the injection sites, making up an apparently continuous horizontal sheet that intersected the striate - extrastriate boundary and merged with the patches of labelled cells in area 18 and beyond. Most of the cells in the 5/6 border band were inverted cells (82%; n= 2081). Injections in area 18 failed to produce such a widespread set of labelled cells in area 17. The functional significance of these connections furnished by the 5/6 border inverted cells remains to be determined, but their distribution would allow for convergent/divergent binding interactions both intra-areally (within area 17) and inter-areally (from area 18 to area 17).
... Overall, these results indicate an orderly variation in synchronicity that seems to closely reflect the presence and density of direct anatomical connections, an idea also suggested by other investigators (see, e.g., [55][56][57][58][59]). These are most dense within an area, substantial across homotopic areas and sparse across heterotopic areas (see, e.g., [60]). ...
We calculated voxel-by-voxel pairwise crosscorrelations between prewhitened resting-state BOLD fMRI time series recorded from 60 cortical areas (30 per hemisphere) in 18 human subjects (nine women and nine men). Altogether, more than a billion-and-a-quarter pairs of BOLD time series were analyzed. For each pair, a crosscorrelogram was computed by calculating 21 crosscorrelations, namely at zero lag ± 10 lags of 2 s duration each. For each crosscorrelogram, in turn, the crosscorrelation with the highest absolute value was found and its sign, value, and lag were retained for further analysis. In addition, the crosscorrelations at zero lag (irrespective of the location of the peak) were also analyzed as a special case. Based on known varying density of anatomical connectivity, we distinguished four general brain groups for which we derived summary statistics of crosscorrelations between voxels within an area (group I), between voxels of paired homotopic areas across the two hemispheres (group II), between voxels of an area and all other voxels in the same (ipsilateral) hemisphere (group III), and voxels of an area and all voxels in the opposite (contralateral) hemisphere (except those in the homotopic area) (group IV). We found the following. (a) Most of the crosscorrelogram peaks occurred at zero lag, followed by ± 1 lag; (b) over all groups, positive crosscorrelations were much more frequent than negative ones; (c) average crosscorrelation was highest for group I, and decreased progressively for groups II-IV; (d) the ratio of positive over negative crosscorrelations was highest for group I and progressively smaller for groups II-IV; (e) the highest proportion of positive crosscorrelations (with respect to all positive ones) was observed at zero lag; and (f) the highest proportion of negative crosscorrelations (with respect to all negative ones) was observed at lag = 2. These findings reveal a systematic pattern of crosscorrelations with respect to their sign, magnitude, lag and brain group, as defined above. Given that these groups were defined along a qualitative gradient of known overall anatomical connectivity, our results suggest that functional interactions between two voxels may simply reflect the density of such anatomical connectivity between the areas to which the voxels belong.
... Second, heterotopic projections were shown to exist from one area to relatively nearby areas. Such a projection was described from the primary somatosensory area to the secondary somatosensory area, intraparietal sulcus, and superior parietal lobule [Pandya and Vignolo, 1968]; from the primary motor cortex to the supplementary motor area and the primary and secondary somatosensory areas [Pandya et al., 1969b]; from the superior temporal gyrus to the middle temporal gyrus and sulcus, the supratemporal plane, the insula, the inferior parietal lobule, and the cingulate cortex, along with a weak projection to the frontal cortex [Pandya et al., 1969a]; and from the inferior parietal lobule to the cingulate gyrus, the medial parietal cortex, the superior temporal sulcus and gyrus, and the occipitotemporal sulcus [Hedreen and Yin, 1981]. ...
Very little is known about the connectivity of the human cerebral cortex. Nonhuman primates often serve as a model, but they are very unsatisfactory when it comes to specifically human functions. Evidence from (human) lesion and activation studies indicates that Broca's and Wernicke's areas play a critical role in language functions, whereas the inferior temporal cortex of the right hemisphere tends to be associated with high-level visual recognition. We describe here monosynaptic interhemispheric input from the right inferior temporal cortex to Wernicke's and Broca's areas. The connections were traced in a brain with a right inferior temporal infarction by means of the Nauta method for anterogradely degenerating axons. Afferents were found both in Broca's and Wernicke's areas, with a higher density in the latter. Three organizational principles emerge from this study. First, the presence of direct connections from the right inferior temporal cortex to the speech areas indicates that human interhemispheric connections can be widely heterotopic. Second, the fact that connections from the inferior temporal cortex terminate in both Wernicke's and Broca's areas speaks in favor of parallel pathways in visuo-verbal processing. And third, the patchy distribution of visual interhemispheric afferents in Wernicke's area hints at a possible functional compartmentalization within this area.
Asymmetries in gray matter alterations raise important issues regarding the pathological co-alteration between hemispheres. Since homotopic areas are the most functionally connected sites between hemispheres and gray matter co-alterations depend on connectivity patterns, it is likely that this relationship might be mirrored in homologous interhemispheric co-altered areas. To explore this issue, we analyzed data of patients with Alzheimer’s disease, schizophrenia, bipolar disorder and depressive disorder from the BrainMap voxel-based morphometry database. We calculated a map showing the pathological homotopic anatomical co-alteration between homologous brain areas. This map was compared with the meta-analytic homotopic connectivity map obtained from the BrainMap functional database, so as to have a meta-analytic connectivity modeling map between homologous areas. We applied an empirical Bayesian technique so as to determine a directional pathological co-alteration on the basis of the possible tendencies in the conditional probability of being co-altered of homologous brain areas. Our analysis provides evidence that: the hemispheric homologous areas appear to be anatomically co-altered; this pathological co-alteration is similar to the pattern of connectivity exhibited by the couples of homologues; the probability to find alterations in the areas of the left hemisphere seems to be greater when their right homologues are also altered than vice versa, an intriguing asymmetry that deserves to be further investigated and explained.
The thalamic pulvinar and the lateral intraparietal area (LIP) share reciprocal anatomical connections and are part of an extensive cortical and subcortical network involved in spatial attention and oculomotor processing. The goal of this study was to compare the effective connectivity of dorsal pulvinar (dPul) and LIP and to probe the dependency of microstimulation effects on task demands and spatial tuning properties of a given brain region. To this end, we applied unilateral electrical microstimulation in the dPul (mainly medial pulvinar) and LIP in combination with event-related BOLD fMRI in monkeys performing fixation and memory-guided saccade tasks. Microstimulation in both dPul and LIP enhanced task-related activity in monosynaptically-connected fronto-parietal cortex and along the superior temporal sulcus (STS) including putative face patch locations, as well as in extrastriate cortex. LIP microstimulation elicited strong activity in the opposite homotopic LIP while no homotopic activation was found with dPul stimulation. Both dPul and LIP stimulation also elicited activity in several heterotopic cortical areas in the opposite hemisphere, implying polysynaptic propagation of excitation. Despite extensive activation along the intraparietal sulcus evoked by LIP stimulation, there was a difference in frontal and occipital connectivity elicited by posterior and anterior LIP stimulation sites. Comparison of dPul stimulation with the adjacent but functionally dissimilar ventral pulvinar also showed distinct connectivity. On the level of single trial timecourses within each region of interest (ROI), most ROIs did not show task-dependence of stimulation-elicited response modulation. Across ROIs, however, there was an interaction between task and stimulation, and task-specific correlations between the initial spatial selectivity and the magnitude of stimulation effect were observed. Consequently, stimulation-elicited modulation of task-related activity was best fitted by an additive model scaled down by the initial response amplitude. In summary, we identified overlapping and distinct patterns of thalamocortical and corticocortical connectivity of pulvinar and LIP, highlighting the dorsal bank and fundus of STS as a prominent node of shared circuitry. Spatial task-specific and partly polysynaptic modulations of cue and saccade planning delay period activity in both hemispheres exerted by unilateral pulvinar and parietal stimulation provide insight into the distributed interhemispheric processing underlying spatial behavior.
The cerebral cortex is the largest and most complex region of the brain. Its development is precisely regulated, first by genetic and molecular mechanisms and later by activity-dependent experience. The formation of correct cortical circuits relies upon initial patterning of the early brain into nascent functional domains, the generation of the precise number and position of neurons, and finally their assembly into functional circuits. Our current understanding of these processes in humans and animal models is based on technologies spanning cellular and molecular biology to advanced magnetic resonance imaging techniques. Here, we review our current understanding of the mechanisms regulating the development of cortical wiring, with a focus on the major interhemispheric and descending projections. Decades of work to understand these basic mechanisms are now being translated to understand the causes of human brain wiring disorders, opening new avenues for the development of therapeutics for brain wiring repair.
In recent years both clinicians and experimentalists have become increasingly interested in the functional significance of interhemispheric relations in brain function. In anatomical terms, this requires a consideration of those structures that interconnect the two cerebral hemispheres:the corpus callosum, anterior commissure, and hippocampal commissures. Perhaps the most basic questions to be posed regarding the anatomy of these structures relates to their composition. What fibers do they transmit? Do all cortical areas have interhemispheric connections? If not, which areas do and which do not?
Very little is known about the connectivity of the human cerebral cortex. Nonhuman primates often serve as a model, but they are very unsatisfactory when it comes to specifically human functions. Evidence from (human) lesion and activation studies indicates that Broca's and Wernicke's areas play a critical role in language functions, whereas the inferior temporal cortex of the right hemisphere tends to be associated with high-level visual recognition. We describe here monosynaptic interhemispheric input from the right inferior temporal cortex to Wernicke's and Broca's areas. The connections were traced in a brain with a right inferior temporal infarction by means of the Nauta method for anterogradely degenerating axons. Afferents were found both in Broca's and Wernicke's areas, with a higher density in the latter. Three organizational principles emerge from this study. First, the presence of direct connections from the right inferior temporal cortex to the speech areas indicates that human interhemispheric connections can be widely heterotopic. Second, the fact that connections from the inferior temporal cortex terminate in both Wernicke's and Broca's areas speaks in favor of parallel pathways in visuo-verbal processing. And third, the patchy distribution of visual interhemispheric afferents in Wernicke's area hints at a possible functional compartmentalization within this area. Hum. Brain Mapping 5:347–354, 1997.
Das Corpus callosum spielt, als die größte interhemisphärische Verbindung, eine entscheidende Rolle bei der Integration und der Koordination von Verarbeitungsprozessen der beiden Großhirnhemisphären. Betrachtet man das Corpus callosum auf mediansagittalen Gehirnschnitten verschiedener Individuen, so wird eine hohe interindividuelle Variabilität in Größe und Form dieser Struktur deutlich, welche die Frage nach der funktionellen Relevanz dieser Differenzen nahe legt. Das Ziel der vorliegenden Arbeit war es daher, mögliche Determinanten und Korrelate dieser Variabilität zu bestimmen und funktionelle Folgen der interindividuellen Unterschiede zu untersuchen.
Zur Bearbeitung dieser Fragestellung wurden vier empirische Studien durchgeführt, in denen die interindividuellen Unterschiede im Aufbau des Corpus callosum mit einer Kombination aus herkömmlicher morphologischer Magnet-Resonanz-Tomografie (MRT) und Diffusions-Tensor-Bildgebung (DT-MRT) erfasst wurden. Die Anwendung der DT-MRT ermöglicht es, über die Beschreibung der Diffusion von Wassermolekülen im Gehirngewebe, Aussagen auch über den mikrostrukturellen Aufbau des Gehirngewebes abzuleiten. Der gewählte methodische Ansatz ging somit über die traditionell makroanatomische Vermessung hinaus und führte zur Erfassung der callosalen Variabilität sowohl auf makro- als auch auf mikrostruktureller Ebene.
In Studie 1 wurde der Effekt von Geschlecht und Händigkeit auf die Variabilität des Corpus callosum untersucht, da von beiden Variablen bekannt ist, dass sie mit Unterschieden in der funktionellen Organisation und Lateralisierung des Gehirns assoziiert sind. Dabei konnte bei Männern im Vergleich zu Frauen bzw. bei Rechts- im Vergleich zu Linkshändern eine größere mediansagittale Schnittfläche gefunden werden. Zudem sprechen die Unterschiede in den gemessenen Diffusionsparametern für eine höhere Dichte von Gewebekomponenten, wie Axone und Oligodendroglia, im Corpus callosum von Männern und Linkshändern. Die Ergebnisse liefern somit einen indirekten Hinweis auf eine mögliche Bedeutung callosaler Variabilität im Kontext der funktionellen Lateralisierung des Gehirns. Direkte Befunde hierzu liefert Studie 2. Hier konnte ein eigenständiger Einfluss der funktionellen Asymmetrie der Großhirnhemisphären auf den Aufbau des Corpus callosum nachgewiesen werden. Am Beispiel der Sprachproduktion wurde gezeigt, dass eine Zunahme der Asymmetrie von aufgabenbezogener Gehirnaktivität (gemessen mit funktioneller MRT) mit einem stärkeren Vorhandensein von Diffusionshindernissen assoziiert ist. Dies kann sowohl als Anzeichen einer dichteren Packung als auch einer stärkeren Myelinisierung der callosalen Axone interpretiert werden. In den Studien 3 und 4 wurden schließlich deutliche Hinweise auf die Bedeutung der interindividuellen callosalen Variabilität für den Informationsaustausch zwischen den Großhirnhemisphären gefunden. Die Transferzeit, gemessen als interhemisphärische Latenzunterschiede in der ereigniskorrelierten Gehirnaktivität nach lateralisierter visueller Stimulation, korrelierte negativ mit der Stärke der Diffusion im posterioren Corpus callosum (Studie 3). Zudem konnte unter Verwendung der Methode der dichotischen Stimulation demonstriert werden, dass die Qualität des interhemisphärischen Transfers auditiver Informationen substanziell von der Größe und vom mikrostrukturellen Aufbau des Corpus callosum abhängig ist (Studie 4). Des Weiteren spricht die Analyse der Diffusionsparameter für eine bedeutsame Rolle der mikrostrukturellen callosalen Variabilität auch bei der aufmerksamkeitsabhängigen Verarbeitung sensorischer Informationen.
In den hier berichteten Arbeiten konnten somit gezeigt werden, dass nicht nur die Schädigung des Corpus callosum (z.B. nach chirurgischer Durchtrennung), sondern auch dessen natürlich auftretende interindividuelle Variabilität eine funktionelle Relevanz besitzt. Vor allem die Betrachtung der mikrostrukturellen Eigenschaften des Corpus callosum hat sich dabei als sehr nützlich erwiesen. Daraus folgt, dass die DT-MRT-Parameter eine wertvolle methodologische Ergänzung darstellen und in Kombination mit der klassischen makrostrukturellen Größenmessung eine umfassende Beurteilung des Corpus callosum erlauben.
The necessity of interhemispheric connections, and the nature of this necessity, are demonstrated by the following hypothetical event. An intelligent being from outer space lands on earth and is asked to design the brain of a cat. The being is intrigued to find that the body of a cat is bilaterally symmetric (he looks himself rather like a multieyed and multiwhiskered octopus).
The ability to direct attention towards behaviorally relevant sensory events within the extrapersonal space is modulated by a complex cerebral network which includes cortical and subcortical components. The posterior parietal cortex of the inferior parietal lobule, the periarcuate region (including the frontal eye fields), and cingulate cortex constitute its three major cortical components. The anatomical connectivity within this network explains why disturbances of directed attention in the form of unilateral neglect emerge after lesions of several widely separated cerebral areas. In the human, clinical and electrophysiological observations suggest that the right hemisphere of the brain is specialized for the processes of directed attention.
Physiological recordings along the length of the upper bank of the superior temporal sulcus (STS) revealed cells each of which was selectively responsive to a particular view of the head and body. Such cells were grouped in large patches 3-4 mm across. The patches were separated by regions of cortex containing cells responsive to other stimuli. The distribution of cells projecting from temporal cortex to the posterior regions of the inferior parietal lobe was studied with retrogradely transported fluorescent dyes. A strong temporoparietal projection was found originating from the upper bank of the STS. Cells projecting to the parietal cortex occurred in large patches or bands. The size and periodicity of modules defined through anatomical connections matched the functional subdivisions of the STS cortex involved in face processing evident in physiological recordings. It is speculated that the temporoparietal projections could provide a route through which temporal lobe analysis of facial signals about the direction of others' attention can be passed to parietal systems concerned with spatial awareness.
The human brain is composed of two broadly symmetric cerebral hemispheres, with an abundance of reciprocal anatomical connections between homotopic locations. However, to date, studies of hemispheric symmetries have not identified correspondency precisely due to variable cortical folding patterns. Here we present a method to establish accurate correspondency using position on the unfolded cortical surface relative to gyral and sulcal landmarks. The landmark method is shown to outperform the method of reversing standard volume coordinates, and it is used to quantify the functional symmetry in resting fMRI data throughout the cortex. Resting brain activity was found to be maximally correlated with locations less than 1 cm away on the cortical surface from the corresponding anatomical location in nearly half of the cortex. While select locations exhibited asymmetric patterns, precise symmetric relationships were found to be the norm, with fine-grained symmetric functional maps demonstrated in motor, occipital, and inferior frontal cortex.
An overview is given of the structure and function of the mammalian cerebral commissures, with an emphasis on their role in interhemispheric communication. A major focus is placed on the use of commis-surotomy as a method of selective disconnection of interhemispheric sensory-motor integration.In order for commissure section to be effective it is crucial that the sensory input is under total experi-menter control. For example, in the split-brain preparation, the optic chiasma must also be sectioned as well as the corpus callosum in order to restrict the monocular visual input to a single hemisphere. Special consideration is given to differences in the commissural organisation in different species. These differences can mean that the same lesion can have different effects in various animal species.Finally, detailed surgical protocols for callosal and chiasma section are given separately for monkey, cat, rabbit, and rat. Each such surgical protocol is specificallytailored to each species' neurosurgical v
This book studies the organization of the white matter pathways of the brain. The book analyzes and synthesizes the corticocortical and corticosubcortical connections of the major areas of the cerebral cortex in the rhesus monkey. The result is a detailed understanding of the constituents of the cerebral white matter and the organization of the fiber tracts. The findings from the thirty-six cases studied are presented on a single template brain, facilitating comparison of the locations of the different fiber pathways. The summary diagrams provide a comprehensive atlas of the cerebral white matter. The text is enriched by close attention to functional aspects of anatomical observations. The clinical relevance of the pathways is addressed throughout the text and a chapter is devoted to human white matter diseases. The introductory account gives a detailed historical background. Translations of seminal original observations by early investigators are presented, and when these are considered in the light of the authors' new observations, many longstanding conflicts and debates are resolved.
The sections in this article are:
The sections in this article are:
The laminar and tangential distributions of association neurons projecting from areas 4 and 6 of the frontal lobe to area 5 of the superior parietal lobule were studied in macaque monkeys by using horseradish peroxidase histochemistry. In both areas 4 and 6 association neurons were medium-large pyramidal cells of layers II and III, and pyramidal and fusiform cells of layers V-VI. Tangentially, they were distributed unevenly over the cortical surface occupying only certain parts of areas 4 and 6, including the dorsomedial part of area 6, the proximal arm region of Woolsey's M1 map, parts of the postarcuate cortex, and the supplementary motor area. Within these projection zones, the number of projection cells waxed and waned in a periodic fashion.
Quantitative methods, including spectral analysis techniques, were used to characterize precisely spatial periodicities along the rostrocaudal dimension. The same quantitative analyses were used to determine the nature of the tangential distribution of corticocallosal cells of area 5 projecting to contralateral area 5. Both association and callosal spectra contained a strong component in the range of low spatial frequencies, corresponding to periods greater than 2 mm. Moreover, a consistent peak was observed in both spectra at spatial frequencies corresponding to periods ranging from 0.85 to 1.28 mm. This peak is in accord with the hypothesis of a modular organization of the cells of origin of these projection systems.
The interhemispheric efferent and afferent connections of the V1/V2 border have been examined in the adult macaque monkey with the tracers horseradish peroxidase and horseradish peroxidase conjugated to wheat germ agglutinin. The V1/V2 border was found to have reciprocal connections with the contralateral visual area V1, as well as with three other cortical sites situated in the posterior bank of the lunate sulcus, the anterior bank of the lunate sulcus, and the posterior bank of the superior temporal sulcus.
Within V1, callosal projecting cells were found mainly in layer 4B with a few cells in layer 3. Anterograde labeled terminals were restricted to layers 2, 3, 4B, and 5. In extrastriate cortex, retrograde labeled cells were in layers 2 and 3 and only very rarely in infragranular layers. In the posterior bank of the lunate sulcus, labeled terminals were scattered throughout all cortical layers except layers 1 and 4. In the anterior bank of the lunate sulcus and in the superior temporal sulcus, anterograde labeled terminals were largely focused in layer 4.
Callosal connections in all contralateral regions were organized in a columnar fashion. Columnar organization of callosal connections was more apparent for anterograde labeled terminals than for retrograde labeled neurons. In the posterior bank of the lunate sulcus, columns of callosal connections were superimposed on regions of high cytochrome activity.
The tangential extent of callosal connections in V1 and V2 was found to be influenced by eccentricity in the visual field. Callosal connections were denser in the region of V1 subserving foveal visual field than in cortex representing the periphery. In V1 subserving the fovea, callosal connections extended up to 2 mm from the V1/V2 border and only up to 1 mm in more peripheral located cortex. In area V2 subserving the fovea, cortical connections extended up to 8 mm from the V1/V2 border and only up to 3 mm in peripheral cortex.
The tangential distributions of callosal neurons of area 5 projecting homotopically to the contralateral hemisphere and of association neurons of areas 4 and 6 projecting to ipsilateral area 5 were determined in the macaque monkey by using neuroanatomical methods based on the retrograde transport of horseradish peroxidase. Both distributions were studied qualitatively through 2-dimensional reconstructions of the cortical areas of origin and quantitatively through a spectral analysis. This approach facilitated the characterization of the spatial periodicities contained in these distributions revealing that, in area 5, callosal neurons were organized in bands of various shapes and width; these bands were composed of more discrete clusters of cells. In the frontal lobe, association neurons projecting to ipsilateral area 5 were arranged similarly. This study suggests that a common principle underlies the tangential organization of both callosal and association projecting cells in different cortical areas and emphasizes a basic similarity of interhemispheric and intrahemispheric connections.
Im ersten Teil der vorliegenden Arbeit wurde im Superfusionsexperiment die Wirkung des aus 28 Aminosäuren bestehenden Amyloid-ß-Proteins (Aß1-28) auf die [³H]-Acetylcholin (ACh)-Freisetzung und [³H]-Cholin-Beladung im menschlichen Neokortex und Rattenhippocampus untersucht. Aß1-28 ist ein synthetisches Derivat des histopathologisch charakteristischen Aß-Proteins des M. Alzheimer, dessen klinische Symptomatik mit einer Störung der cholinergen Neurotransmission in Verbindung gebracht wird.
Die Kalium (20 mM, 60 min)-evozierte [³H]-ACh-Freisetzung wurde in beiden Spezies durch Aß1-28 (0.1 nM) gehemmt. Die Verlängerung der Einwirkzeit des Aß1-28 verstärkte die Inhibition. Keine Zunahme der Hemmung bewirkte bei der Ratte die Variation des zur Präparation von Aß1-28 eingesetzten pH-Werts, mit der der Effekt des Aß1-28 in veränderter Sekundärstruktur untersucht wurde.
In 0.1 nM Konzentration steigerte Aß1-28 bei der Ratte die [³H]-Cholin-Beladung, beim Menschen erst bei 1 nM. Die Verlängerung der Einwirkdauer führte lediglich im menschlichen Gewebe zu einer weiteren Zunahme der radioaktiven Beladung. Wiederum blieb die Variation des pH-Werts ohne zusätzlichen Effekt im Rattenhippocampus.
Im zweiten Teil wurde die Aktivierung der Cholin-Acetyltransferase (ChAT) in menschlichem Neokortexgewebe durch Depolarisation untersucht. Im Superfusionsexperiment mit Gabe der ChAT-Inhibitoren Okadasäure (50 nM) und Bromo-ACh (30 µM) wurde die Aktivierung der ChAT mittels Kalium (20 mM, 4 min)-Depolarisation indirekt demonstriert, während bei elektrischer Stimulation (3 Hz, 90 Pulse a‘ 2 ms, 68 mA) die entsprechende Wirkung der Okadasäure ausblieb. Mittels ChAT-Assay wurde die Aktivierung der ChAT durch vierminütige Kalium-Depolarisation direkt nachgewiesen.
The efferent projections of the neocortex on the lateral convexity of the inferior parietal lobe (area 7 of Brodmann) were examined using the anterograde transport of tritiated amino acids. Multiple injections of 3H-leucine and 3H-proline were placed within the three cytoarchitecturally distinct zones that lie along the exposed surface of the inferior parietal lobe (IPL). The subcortical projections resulting from these injections were studied. Prominent projections were seen in the thalamus (medial and lateral pulvinar), brainstem (dorsolateral and ventral pontine nuclei), and basal ganglia (caudate and putamen) with less dense label over the thalamic intralaminar nuclei, pretectal complex, superior colliculus, reticular nucleus of the thalamus, suprageniculate nucleus, lateral posterior nucleus, oral pulvinar, and claustrum. In many of these cases there was a topographical relationship apparent with regard to the injections placed along the rostral-caudal dimension of the IPL. There is a striking reciprocal arrangement in the afferent and efferent projection systems of the IPL. The functional relevance of both the topography and the efferent projections of the IPL is discussed.
The cortex of the upper bank of the superior temporal sulcus (STS) in the rhesus monkey contains a region that receives overlapping input from post-Rolandic sensory association areas and is considered multimodal in nature. We have used the fluorescence retrograde tracing technique in order to answer the question of whether multimodal areas of the STS project back to post-Rolandic sensory association areas. Additionally, we have attempted to answer the question of whether the projections from the multimodal areas directed to the parasensory association areas originate from common neurons via axon collaterals or from individual neurons. The results show that multimodal area TPO of the STS projects back to specific unimodal parasensory association areas of the parietal lobe (somatosensory), superior temporal gyrus (auditory), and posterior parahippocampal gyrus (visual). In addition, a substantial number of projections from area TPO are directed to distal parasensory association areas, area PG-Opt in the inferior parietal lobule, areas Ts1 and Ts2 in the rostral superior temporal gyrus, and areas TF and TL in the parahippocampal gyrus. These latter regions are themselves considered to be higher-order association areas. It was also noted that the majority of the projections to these higher-order association areas originate from the middle divisions of area TPO (TPO-2 and TPO-3). These neurons are organized in a significantly overlapping manner. Despite this overlap of the projection neurons, only an occasional double labeled neuron was observed in area TPO. Thus, our observations indicate that the multimodal region of the superior temporal sulcus has reciprocal connections with the unimodal parasensory association cortices subserving somatosensory, auditory and visual modalities, as well as with other post-Rolandic higher-order association areas. These connections from area TPO to post-Rolandic association areas may have a modulating influence on the sensory association input leading to multimodal areas in the superior temporal sulcus.
The pattern of commissural connections of the rat auditory cortex (AC) was investigated with injections of wheat germ agglutinated horseradish peroxidase into the AC. Homotopic and heterotopic patches of neurons were retrogradely labeled in the contralateral hemisphere. Each injection labeled neurons at the corresponding contralateral site, i.e. the homotopic site. In addition, retrogradely labeled neurons were found at non-corresponding locations in contralateral AC, i.e. at heterotopic locations. The pattern of heterotopic labeling changed systematically with the injections. Mapping rules were established that led to the parcellation of areas 41 and 36 into 6 fields. Four fields were defined in Krieg's area 41 (primary AC) and two fields in Krieg's area 36 (secondary AC). In area 41 the heterotopic connection is not reciprocal; in area 36, however, heterotopic projections are organized reciprocally. Contrary to the visual cortex, homotopic and heterotopic projection neurons were equally distributed across the cortical laminae. With double-label experiments it could be shown that a considerable number of the neurons in area 41 bifurcate and project to homotopic as well as to heterotopic sites in the contralateral hemisphere. We conclude that in the AC there are several subtypes of neurons projecting to the contralateral hemisphere; it would be of interest whether these anatomical differences are manifested by physiological differences.
The callosal connections of area 7b, PF, in the monkey have been studied after injections of HRP into this area in one hemisphere. On the opposite side labelled cells were present in area 7b and in certain areas that are connected with it, area 5, SII and the insular granular area. In these areas the cells are in the representations of all parts of the body except that of the distal forelimb.
The cortico-cortical connections of area 7b (or PF) in the parietal and temporal lobes of the monkey have been studied with the method of axoplasmic transport of horseradish peroxidase (HRP). Area 7b is reciprocally and precisely connected with area 5, the second somatic sensory area (SII), the retroinsular area, the granular insular area (Ig), area 23 of the cingulate cortex and with the cortex in the walls of the superior temporal sulcus. Area 7b is not interconnected with area 7a (PG) nor with any of the prestriate visual areas. After injections of HRP into area PF the labelled cells in all these areas, except the granular insular area, are mainly in layer III and these cells are considered to be the origin of 'feed-forward' type connections; in the granular insular area most of the cell labelling is in layer V, interpreted to be the origin of 'feed-back' connections. Between SI and area PF there are two sequences of connections in parallel with each other, one through area 5 and the other through SII. In all areas the labelled cells are in clusters of 500-2000 microns width on individual sections and in bands of these widths on planar reconstructions.
The relationship between the termination zones of projections from paired homotopic areas of the frontal lobes was examined in the caudate nucleus and the putamen of the macaque monkey. Injections of WGA-HRP and tritiated amino acids were made in topographically matched regions of the principal sulcus (PS) or of the supplementary motor area (SMA) in each hemisphere, such that the projections from the same area on each side were differentially labeled in the same animal. Adjacent sections through the neostriatum were processed for the respective tracers, permitting the relationship between the converging projections to be defined.
The topographic distribution and strength of ipsilateral corticostriatal projections observed for separately labeled left and right hemispheres were strikingly similar. Projections from the left and the right PS terminated preferentially in central parts of the left and right neostriata, respectively, while projections of the left and right SMAs terminated preferentially in dorsolateral parts of respective left and right neostriata. Therefore, little evidence for asymmetry of corticostriatal projections was found.
The projections of the left and the right PS to the same neostriatum were also compared. Remarkably, whether in the left or right hemisphere, projections from the left and the right PS were in precise register in topographically specific territories of the caudate and putamen. Likewise, projections of the left and right SMAs converged in both the left and right neostriata. Such convergence allows for a remarkable degree of interhemispheric integration in the descending corticostriatal networks.
The relationship between the termination zones of projections from paired homotopic areas in the frontal lobe was examined in the cerebral cortex of the macaque monkey. Injections of WGA-HRP and tritiated amino acids were made in topographically matched regions of the principal sulcus (PS) or the supplementary motor area (SMA) in each hemisphere, such that the projections from the same area on each side were differentially labeled in the same animal. Adjacent sections through the cortical regions that received bilateral inputs from these areas were processed for the respective tracers, permitting the relationship between the converging projections to be defined.
Comparison of the cortical connections of the left and right PS or of the left and right SMA yielded two major findings. First, only minor differences in the topographic distribution and strength of connections of homotopic areas were observed, providing little evidence of asymmetry in the connections of either the PS or the SMA in the macaque. Second, with the exception of interdigitation observed in a portion of the dorsal bank of the PS, the cortical projections from both the left and the right PS and SMA converged (overlapped) in common columnar territories. These termination patterns allow for a remarkable degree of interhemispheric integration.
The interhemispheric connections of the cortical areas of the temporal lobe and some neighboring regions were investigated in monkeys ( Macaca mulatta and Macaca fascicularis ) by anterograde autoradiographic tracing, following injection of radioactively labeled amino acids. The results revealed that the interhemispheric projections of the temporal lobe course through three interhemispheric commissures on their way to the opposite hemisphere. The anterior commissure receives fibers from virtually the entire temporal lobe, including the temporal pole, superior and inferior temporal gyri, and parahippocampal gyrus. Moreover, area 13 of the orbitofrontal cortex, the frontal and temporal subdivisions of the prepiriform cortex, and the cortical and deep nuclei of the amygdala also contribute fibers to the anterior commissure. The heaviest projections arise in the rostral third of the temporal isocortex. These projections become progressively lighter from more caudal regions.
By contrast, the corpus callosum receives fibers from the caudal two‐thirds of the temporal lobe, including the temporal pole, superior and inferior temporal gyri, and parahippocampal gyrus. The heaviest projections arise in the caudal third of the temporal lobe and cross primarily in the caudal third of the corpus callosum, including the splenium. Progressively lighter projections arise more rostrally. Fibers from proisocortical and isocortical areas of the posterior parahippocampal gyrus cross in the ventralmost part of the splenium ( inferior forceps ), whereas cortical areas lateral to the occipitotemporal sulcus give rise to fibers that cross in the caudal part of the body of the corpus callosum and dorsal splenium. The dorsal hippocampal commissure receives fibers exclusively from the parahippocampal gyrus.
The fibers of the corpus callosum, hippocampal commissure, and, to a lesser extent, the anterior commissure are intimately associated with the ventricular system as they course through the white matter of the temporal lobe. The fields of origin of the anterior commissure and corpus callosum overlap extensively over the caudal two‐thirds of the temporal lobe. The posterior parahippocampal gyrus is unique in that it gives rise to fibers that cross in all three commissures.
Experiments were made on the cortex of the inferior parietal lobule in 10 hemispheres of six alert, behaving monkeys. The electrical signs of the impulse discharges of single cortical cells were recorded as the monkeys executed tasks requiring them to fixate stationary visual targets, track those which moved slowly, and to make saccadic movements to foveate those which suddenly jumped from one locus to another within the field of view. A total of 907 neurons of area 7 were identified in terms of their physiological properties, particularly the correlation of their activity with the oculomotor components of these behavioral acts of directed visual attention; 480 of these were located by cytoarchitectural layer. Most identifiable cells of area 7 are visuomotor neurons, in a special and conditional sense. Their discharge frequencies increase before and during those steady fixations and movements of the eyes which secure and maintain foveation of objects, but only if the visual targets engaged are linked by a strong motivational drive; in these experiments, one between thirst and the light dimming the animals has learned to detect for liquid reward. The authors have identified and studied three major classes of neurons in area 7.
The functional role of the posterior parietal association cortex was studied by observing the relationship between cellular discharges in Brodmann’s area 7 and behaviour in non-anaesthetized monkeys. Of the 193 cells investigated with a transdural microelectrode technique the majority were related to sensory and motor functions of the opposite side. In many cells a discharge was produced when a sensory stimulus which interested the animal was placed in a specific location in space where it became the target of the monkey’s gaze or manual reaching, tracking, or manipulation. Convergence of touch and visual stimuli related to the same body part was also observed. Some cells weie clearly related to eye movements whereas others appeared to discharge in response to visual sensory stimuli. Functionally similar cells were grouped together, possibly in columns, and neighbouring groups were activated by stimuli from different directions and by different mechanisms. The sensory input to these cells is likely to be from the ascending sensory systems through cortico-cortical piojections and through the pulvinar, whereas the output from area 7 is to the motor systems. In this way the sensory signals relayed with reference to spatial locations to the cells of the posterior association cortex can be used to guide the motor systems during voluntary movements aimed at targets placed at various spatial locations. On the basis of these results, the normal function of the cells in this region is to convey visual and somaesthetic signals from the opposite side to the level of sensation and to the motor systems for directing motor responses to targets. These findings provide a physiological basis foi explaining the spatial disorientation syndromes produced by lesions of the posterior parietal cortex in man.
The object of this investigation was to trace by the so-called anatomical method the degeneration resulting from minute lesions of the motor area of the cortex cerebri through the brain and spinal cord, to locate the path of the conducting fibres in the internal capsule and elsewhere, to follow them as far as possible to their destinations, and by such control observations to check off the results obtained by previous excitation experiments.
This article, written on the 60th anniversary of Korbinian Brodmann's death, discusses his schematic cytoarchitectonic chart of the cerebral cortex in relation to the brain sections from which it was derived and draws attention to the discrepancies between the two.
Fibers from the upper opercular striate cortex pass to the following structures in the following order of abundance of association fibers: (a) Remainder of upper half of striate cortex including medially located portions. (b) Lower macular cortex. (c) Rest of striate cortex. (d) Posterior limb of the angular gyrus and middle annectant gyrus. (e) Caudal end of the posterior superior, parietal gyrus.
Cyto- and myeloarchitectonic investigation of the temporal operculum and the exposed superior temporal gyrus was combined with a connection study of the projection fibers of the pertinent areas in the rhesus monkey. A belt-like organization of the auditory region with a koniocortex core (corresponding to AI) surrounded by belt areas was revealed. This organization principally resembled that of the auditory region of the cat (Rose and Woolsey, 1949; Woolsey, 1961) and that of other sensory regions (Sanides, 1972; Sanides and Krishnamurti, 1967). The belt is composed of one prokoniocortex area (proA, corresponding to AII) in parinsular location and of a caudal (paAc), lateral (paAlt) and rostral (paAr) parakoniocortex area. The latter has a particular character. It was found to be the target of thalamic projections of the caudalmost portion of GMpc. In contrast to the other parakonio areas it does not receive associations of the koniocortex. The koniocortex core is formed by two areas, Kam and Kalt, corresponding to the architectonic organization hitherto only known in man. The medial area (Kam) has a large number of homotopical callosal projections except at its medial border (to proA). The lateral area receives less callosal fibers, particularly most of its lateral portion is devoid of terminations. Since the belt areas are rich in callosal projections the supratemporal plane shows a pattern of three stripes of callosal terminations with two intermittent stripes void of terminations. In contrast to other sensory regions the auditory koniocortex receives its exceptionally dense, homotopic callosal connections in the whole outer stratum with emphasis on layer III, as opposed to layer IV in the somatic sensory region.
In 6 adolescent rhesus monkeys, horseradish peroxidase (HRP) was injected into 6 regions of the dorsolateral convexity of the prefrontal granular cortex.The commissural connections originated in both homotopical and heterotopical zones of the hemisphere contralateral to the injection site. The areas affected by the injections, i.e. areas 46, 45, 10, 9, 12 and 8a, received extensive homotopical interhemispheric input. HRP-labeled neurons were less extensive in heterotopical as opposed to homotopical cortex but they were seen in all 6 cases and were most common in prefrontal areas and less common in cingulate areas, areas 21 and 22 in the superior temporal sulcus and in insular cortex. The cells, whether of heterotopical or homotopical origin, were located primarily in layer III. The most common distribution pattern was a horizontal band of HRP-labeled neurons which waxed and waned in cell density especially in homotopical cortex or patches and clusters of labeled cells especially in heterotopical cortex.This waxing and waning and grouping of neurons in patches and clusters may well represent a vertical type of organization to the neurons which give rise to the interhemispheric cortical afferents to prefrontal granular cortex in the monkey.
In four macaque monkeys horseradish peroxidase (HRP) was injected into physiologically defined hand-arm motor area. Ipsilaterally, HRP labeled neurons were found in both upper and lower limbs of the posterior bank of the arcuate sulcus and in an area surrounding the arcuate spur. Contralaterally, labeled neurons were found in the same areas, though less dense in concentration. Labeled neurons were found mostly in layer III of the cortex.
Horseradish peroxidase (HRP) injections at the boundary of areas 17 and 18 in cat visual cortex resulted in retrograde labelling of neurones located in contralateral areas 17 and 18. The HRP-positive neurones were spread over a region located around the representation of the vertical meridian; they were most numerous in the locus for area centralis. Layer III pyramidal cells and stellate cells in upper layer IV were identified as the principal neurones of origin of the visual callosal pathway.
Projections to the inferior parietal lobule were studied by retrograde axonal transport of horseradish peroxidase (HRP). Several cortical and subcortical areas projected to both areas PF and PG including the cingulate and periarcuate cortex, the basal nucleus of Meynert, several intralaminar nuclei of the thalamus, and the ventral lateral thalamic nucleus. However, area PF received afferents from the second somatosensory area of the parietal operculum, the oral pulvinar nucleus, and ventral parts of the medial pulvinar nucleus, whereas area PG received imputs from the banks of the superior temporal and occipitotemporal sulci and from the dorsal parts of the medial pulvinar and lateral posterior nuclei.
Corticostriatal cells in rat neocortex were identified by the peroxidase retrograde axonal transport method as neurons restricted to layer V, found in the whole radial extent of layer V, and comprising cells of all sizes and shapes. Usually the largest pyramidal cells were not labeled.
In 5 squirrel monkeys the anatomical projections from the ‘cingular’ vocalization area were studied by the autoradiographic tracing technique. The ‘cingular’ vocalization area lies around the sulcus cinguli at the level of the genu of the corpus callosum; its electrical stimulation yields purring and cackling calls. The following efferent connections were found: corticocortical fibers could be traced into the orbital cortex (areas 10 and 11), dorsomedial frontal cortex (areas 9, 8 and 6), limbic cortex (areas 25, 24 and 23), Broca's area (area 44), frontal operculum (area 50), insula (areas 13 and 14), and auditory association cortex (area 22). Subcortical terminal fields within the telencephalon were found in the nucleus caudatus, putamen, claustrum, globus pallidus, olfactory tubercle, preoptic region and nucleus centralis and basolateralis amygdalae. Fibers reached most of these structures along different trajectories. In the diencephalon terminal fields lay in the dorsal hypothalamus, the subthalamus, lateral habenular nucleus, and the following thalamic nuclei: nucleus reticularis, ventralis anterior, centralis medialis, centralis superior lateralis, centralis inferior, submedius, medialis dorsalis and centrum medianum. In the midbrain, the periaqueductal gray was the only projection area, extending into the parabrachial nuclei at the pontomesencephalic transition. The most caudal terminal field was found in the medial pontine gray. No terminals were detected in the nucleus ambiguus, nucleus n. hypoglossi or in any other cranial motor nucleus involved in phonation processes.
Horseradish peroxidase (HRP) was injected into the first (SI) or second (SII) somatosensory areas of 21 adult cats. The radial and tangential (normal and parallel to the pial surface, respectively) distribution and morphology of the callosal neurons were studied. HRP injections were combined with single unit recording in the contralateral cortex in order to determine which part of the somatosensory periphery is represented within the regions containing callosal neurons, the callosal (efferent) zones, in SI and SII. The callosal zone of SI extends over the trunk and part of the forepaw representation. In the forepaw and hindlimb representations callosal neurons projecting only to the contralateral SII are found, while in the trunk representation callosal neurons projecting to contralateral SI or SII are found. The callosal zone in SII extends widely throughout the forepaw representation in this area and projects to the contralateral SII but not to SI.
In both SI and SII the callosal neurons are mainly located in layer III. A few of them are also found in layer VI. They are very rare in other layers. Callosal neurons in layer III are mostly pyramidal but exceptionally stellate; in layer VI they are pyramidal, triangular, and occasionally stellate.
These data indicate that transformations of the cortical somatosensory maps are achieved in the message sent through the corpus callosum. These transformations are i) determined by the extent and location of the callosal zones and perhaps by the distribution of callosal neurons within them, ii) different in different areas, iii) different in a same area, according to the cortical targets to which they are conveyed. The existence of callosal connections originated from areas of distal forepaw representation supplies a possible anatomical substrate for those types of intermanual transfer of tactile learning which depend upon the integrity of the corpus callosum.
Recent experiments by Mountcastle and colleagues have described cells in posterior parietal cortex of the rhesus monkey (area 7) that discharge in association with eye movements and hand movements. We have studied the activity of cells in area 7 during visually guided saccadic eye movements, visual fixations, smooth-pursuit eye movements, and visually guided hand projection movements. We have found that any cell that fires in association with a movement can be driven by a passive sensory stimulus, one delivered in the absence of movement. Frequently the identical stimulus that evokes the movement is adequate. Although we have classified neurons according to the movements with which they can be associated, we propose that such a classification be abandoned, and that parietal cells, which have sensory responses, be described according to these sensory properties. It was concluded that posterior parietal cortex is composed of neurons with sensory responses, some of which associate information from the visual and somatosensory environment with internal data. Parietal neurons respond to sensory stimulation in the absence of movement, but do not fire in association with movement in the absence of a stimulus. When a light is the target for a movement, the sensory response can be enhanced. Nonetheless, for all parietal neurons, discharge is indicative of the presence of a stimulus and not predictive of movement. Their data do not support the claim that these neurons perform a 'command function'. The authors suggest that posterior parietal cortex is related to visual attention; in this context it is related to movement but dissociable from it.
The subicular cortices of the primate hippocampal formation form a physical and connectional link between the cortex of the temporal lobe and the hippocampus. Their direct connections with all classes of cortex in the temporal lobe except primary sensory cortex underscore the pivotal role of these areas in the potential interplay between the hippocampal formation and the association cortices.
This article, written on the 60th anniversary of Korbinian Brodmann's death, discusses his schematic cytoarchitectonic chart of the cerebral cortex in relation to the brain sections from which it was derived and draws attention to the discrepancies between the two.
The full extent of the cortical field of origin of the anterior commissure of the rhesus monkey was mapped by horseradish peroxidase (HRP) histochemistry. Two adult monkeys were first subjected to complete callosal commissurotomies and permitted to fully recover 6 months prior to a second operation involving the massive unilateral injection of HRP into the entire left temporal lobe. Because the anterior commissure is the only direct fiber system ramifying to the contralateral cerebral cortical hemisphere following callosotomy, the only cells labeled with HRP in the uninjected hemisphere are those giving rise to the anterior commissure. Only layer III cortical pyramidal cells were labeled by HRP. The outer boundaries of the field of origin of the anterior commissure extend from the temporal pole to the occipitotemporal border and from the inferior half of the insular cortex to the parahippocampal gyrus. The field of origin delineated in the present investigation is much more extensive than the terminal projection field of the anterior commissure delineated by prior investigators utilizing silver degeneration methods.
The topographical organization of the contralateral cortical projections of the motor hand area was studied with autoradiographic methods in 11 macaque monkeys.
Two general observations were noted in the material studied. (1) The commissural cortico-cortical connections of the motor hand area were directed to the contralateral precentral gyrus. The projections were preferentially directed to both homotopic and non-homotopic areas. (2) Focally labeled areas of motor cortex (diameter 900 μm) gave rise to individual terminal columns of label (diameter 600–900 μm). Larger areas of labeled motor cortex, (3,000 μm in diameter) gave rise to contralateral terminal bands of label. These bands (600–1,000 μm in width) were oriented in an antero-posterior direction and appeared to be formed by a sequence of adjacent labeled columns.
Callosally projecting cells and the terminal ramifications of their axons were identified in the monkey sensory‐motor cortex by retrograde and anterograde labeling techniques, often by double labeling cells and axons in the same animal.
Bundles of callosal fibers terminate in small column‐like zones 0.5‐1 mm wide in the motor cortex (area 4) and in the first (SI) and second (SII) somatic sensory areas. Such columns are aligned in register to form elongated strips extending mediolaterally in the long axes of the pre‐ and postcentral gyri. Significant portions of area 4, SI and SII, in regions corresponding to the representations of the hand and foot, are not callosally connected.
The cells of origin of callosal fibers in SI are largely confined to layer IIIB and form columns and strips corresponding to the above. In connected zones of SI, the callosal connection is reciprocal and precisely point‐to‐point. This and the laminar distribution of the terminal ramifications of callosal fibers (to layers I‐IV) suggest that callosal fibers may arise from and terminate upon exactly homotopic, column‐like groups of layer IIIB pyramidal cells.
Commissurally projecting cells and their terminal ramifications are not limited to particular architectonic fields or particular parts of fields in SI. All architectonic fields of SI project heterotopically to the contralateral SII.
Efferent cortical projections of posterior parietal cortex were determined by degeneration and autoradiographic methods in owl monkeys. Intraregional connections were to the immediate surround of the injection or lesion site, and to distinct foci within the posterior parietal region. The extraregional ipsilateral connections were with (1) previously established subdivisions of visual association cortex (the Dorsomedial Area, the Medial Area, the Dorsolateral Area, and the Middle Temporal Area), (2) other locations in caudal neocortex, and (3) frontal cortex. The callosal projections were to separate foci in posterior parietal cortex of the contralateral cerebral hemisphere. The separate foci of both ipsilateral and contralateral terminations in posterior parietal cortex raise the possibility that this region contains more than one functional subdivision. The connections with visual association cortex suggest a role for parietal cortex in visual behavior. Other foci in caudal neocortex indicate the possible locations of additional subdivisions of association cortex.
The sources of afferent connections to the inferior parietal lobule (rostral part of the area 7 of Brodman; PF and rostral part of PG of von Bonin and Bailey) were examined with the retrograde transport method in infant and adult rhesus monkeys. Two to 3 days after injections of horseradish peroxidase (HRP) into the cortex, the animals were anesthetized, and the brains fixed and processed for the histochemical demonstration of the enzyme marker. Labeled neurons were found in layer III in the ipsilateral prefrontal, parietal, occipital and temporal cortices, notably in areas 5, 19, 22 and 46 of Brodmann, and in area 7 of the contralateral parietal cortex. In the thalamus, HRP-positive cells were located ipsilaterally in the medial pulvinar nucleus in the nuclei centrum medianum and parafascicularis, as well as in the rostral thalamus, lateral and medial to the mammillothalamic tract, in the nucleus ventralis anterior and nucleus paracentralis. Numerous labeled cells were also identified in the magnocellular nuclei of the basal forebrain, in the dorsal and medial raphe nuclei, and in the locus coeruleus. Most of the cells in these regions were located in the hemisphere ipsilateral to the injections, but a number of them were also found in the contralateral hemispher. In adult monkeys, brownish granules in the cytoplasm of some cells were interpreted as endogenous pigment or due to various pigment precursors. However, all 14 locations listed above were identified in the infant monkey in which endogenous pigment was not a confounding factor.
The terminal distribution of cortico-cortical connections was examined by autoradiography 7–8 days following injections of tritium labeled amino acids into the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex in monkeys ranging in age from 4 days to 5.5 months. Labeled axons originating in these various regions of the frontal lobe have topographically diverse ipsilateral and contralateral destinations but virtually all of these projections share a common mode of distribution: they terminate in distinct vertically oriented columns, 200–500 μm wide, that extend across all layers of cortex and alternate in regular sequence with columns of comparable width in which grains do not exceed background. Spatial periodicity in the pattern of transported label in such regions as the prefrontal association cortex, the retro-splenial limbic cortex and the motor cortex indicates that columniation in the intra-cortical distribution of afferent fibers is not unique to sensory specific cortex but is instead a general feature of neocortical organization.
A columnar mode of distribution of cortico-cortical projections is present in monkeys at all ages investigated but is especially well delineated in the youngest of them. Thus, grain concentrations within columns are very high in monkeys injected at 4 days of age, somewhat lower in monkeys injected at 39–45 days of age, and least dense in those injected at 5.5 months. The distinctness of the spatially segregated pattern of innervation in the cortex of neonates indicates that the columnar organization of association-fiber systems in the frontal and limbic cortex is achieved before or shortly after birth.
Pulvinar-latero posterior afferents to the parietal cortical area 7 of the monkey have been demonstrated by means of horseradish peroxidase (HRP) tracing technique. Following HRP injection of area 7, labelled neurons have been found in the pulvinar medialis and the nucleus lateralis posterior. The role of these pulvinar projection fibers is discussed with reference to the "visual neurons" of area 7 recently recorded from.
A newly identified class of neurons of the parietal cortex, studied in waking monkeys (Macaca mulatta), is activated by visual stimuli, perhaps via the retino-collicular visual pathway. This afferent input is thought to provide the visual cues activating the visuomotor mechanisms of the parietal lobe for the direction of visual attention.
The cells of origin of cortico‐cortical and subcortical projections from the subfields of the somatic sensory area and from the motor cortex have been identified in cynomolgus and squirrel monkeys by the retrograde axonal transport method.
The somata of the cells of origin of a particular fiber system have a specific laminar or sublaminar distribution. The somata of the majority of cortico‐cortical cells lie in the supragranular layers. Those projecting to the opposite cortex are confined to the deeper half of layer III (layer IIIB). Ipsilateral cortico‐cortical neurons lie mainly superficial to them in layers IIIA and II, but in the second somatic sensory area (SII) and in area 2 of the first (SI), small numbers are also found in layer V. Corticospinal cells lie in the deeper part of layer V and corticostriatal cells in the superficial part. Corticopontine, corticobulbar and corticorubral cells lie in between. The majority of corticothalamic cells lies in layer VI but a second, smaller population is found in the deep part of layer V.
The cells giving rise to a particular set of efferent connections can be distinguished in terms of size and, with the exception of the corticospinal cells, their size does not vary greatly from area to area. In many cases, the size and laminar specificity indicates that cells sending axons to one site cannot have collateral branches projecting to another.
In most of the fiber systems studied, labeled cells form single or multiple strips, 0.5–1 mm wide and oriented mediolaterally across the cortex. The strips appear in all of the subfields of the somatic sensory and motor areas and may form the basis of the clustering of like groups of efferent neurons demonstrable in physiological studies.
The caudal part of the inferior parietal lobule (area PG) was injected with horseradish peroxidase (HRP) in 6 hemispheres of 5 rhesus monkeys. The retrograde transport of HRP resulted in the labeling of neurons in diverse cortical and subcortical areas. In cortex, labeled neurons were noted in prefrontal cortex (areas 8, 45, 46), in the banks of the intraparietal and superior temporal sulci, in medial parietal cortex, in cingulate cortex, in the retrosplenial area, in area TF and the caudal portions of the parahippocampal region. Subcortical sites with labeled neurons included the necleus basalis of the substantia innominata, the claustrum, the pulvinar and intralaminar thalamic nuclei, the pretectal area, the nucleus locus coeruleus and the raphe nuclei. Although many of the labeled neurons were seen in layers IIIc and V, each cortical area had an individual laminar pattern of labeled neurons. In these experiments, a benzidine dihydrochloride (BDHC) method was used which yields a blue reaction-product at sites containing HRP. BDHC affords superior visibility of labeled neurons, and a significant improvement in sensitivity when compared to a diaminobenzidine procedure in matching series of sections. Additional sections were also stained with a method which allows the simultaneous demonstration of HRP (blue) and acetylcholinesterase (reddish-brown). These revealed that virtually all substantia innominata (nucleus basalis) neurons which project to area PG are also rich in the enzyme acetycholinesterase. These afferents of PG may be classified into 'sensory association', 'limbic' and 'reticular' categories. It is argued that this arrangement of afferent imput may afford a convergence of limbic and sensory information in area PG and that this may subserve a significant function in the process of sensory attention.
The inferior parietal lobule (IPL) of the monkey is the homologous region to the supramarginal and angular gyri in man, subserving language and related cortical functions. We have examined specific zones of the IPL by injecting eight monkeys with retrogradely transported HRP, and located the positive cells in the thalamic sections with the assistance of an X‐Y plotter and reference to the atlas of Olszewski ('52). Projections to the IPL were found in the following thalamic nuclei: Anterior (Anterior Medial, Anterior Ventral); Lateral (Ventral Anterior, Ventral Anterior magnocellularis, Ventral Lateral caudalis, Pulvinar oralis, medialis, lateralis and inferior, Lateral Posterior and Lateral Dorsal); Medial (Medialis Dorsalis densocellularis, parvocellularis, and multiformis); Midline and Intralaminar (Centralis densocellularis, Centralis lateralis, Centralis inferior, Centralis superior lateralis, Subfascicularis parvocellularis, Paracentralis and Parafascicularis); and Posterior (Limitans, Suprageniculatus and Geniculatus Medialis magnocellularis).
A major projection to the superior portion of the IPL was from the anterior nuclei and Paracentralis of the intralaminar group. Ventralis Lateralis and oral Pulvinar projected primarily to the anterior‐inferior portion of the IPL, whereas Lateral Posterior projected most strongly to the anterior and superior portion. The major projection of the lateral Pulvinar was to the mid‐superior portion of the IPL and to area 19. The projections of the inferior Fulvinar were heaviest to area 19, but there was some overlap in the mid‐superior portion of the IPL with the medial and lateral Pulvinar. The major projection from the posterior thalamic nuclear complex was to the mid‐IPL.
The heterogeneous input from the thalamus to the IPL was not anticipated on the basis of prior anterograde or retrograde degeneration studies, and suggests that classical subdivisions of specific and associational thalamic nuclei should be revised with the axonal transport methods of study.
The efferent connections of the cortex projected upon by the mediodorsal thalamic nucleus (MD-projection cortex) have been re-examined autoradiographically in the rat following the microelectrophoretic injection of ³H-proline-leucine into different parts of the medial and sulcal MD-projection cortex. Contrary to previous negative findings, the present experiments revealed a system of extensive corticocortical projections and indicated that different areas of the MD-projection cortex have distinctive patterns in both their corticocortical and subcortical projections. Thus, cell of Brodmann's area 32 send axons to the retrosplenial cortex, area 29d, the peri- and entorhinal cortices, and the presubiculum. Both supragenual and more posterior regions of area 24 project to the retrosplenial cortex and area 29d, but only the posterior portion projects additionally to the entorhinal area and presubiculum. The cortical targets of axons from the sulcal MD-projection cortex are mainly the anterior part of the piriform cortex and, for the posterolateral part of the sulcal cortex (insular area), the retrosplenial area, lateral entorhinal area, and presubiculum. While the medial and sulcal divisions of the MD-projection cortex project upon one another, the medial-to-sulcal projection is in general denser than its reciprocal.