Contralateral thalamic projections predominantly reach transitional cortices in the rhesus monkey

Connections between the thalamus and the cortex are generally regarded as ipsilateral, even though contralateral connections exist as well in several adult mammalian species. It is not known however, whether contralateral thalamocortical projections reach particular cortices or whether they emanate from specific nuclei. In the rhesus monkey different types of cortices, ranging from transitional to eulaminate, vary in their cortical connectional pattern and may also differ in thier thalamic connections. Because olfactory and transitional prefrontal cortices receive widespread projections, we investaged whether they are the target of projections from the contralateral thalamus as well. With the aid of retrograde tracers, we studied the thalamic projections of primary olfactory (olfactory tubercle and prepiriform cortex) and transitional orbital (areas PAPP, Pro 13) and medial (areas 25, 24, 32) areas, and of eulaminate (areas 11, 12, 9) cortices for comparison. To determine the prevalence of neurons in the contralateral thalamus, we compared them with the ipsilateral in each case. The pattern of ipsilateral thalamic projections differed somewhat among orbital, medial, and olfactory cortices. The mediodorsal nucleus was the predominant source of projections to orbital areas, midline nuclei included consistently about 25% of the thalamic neurons directed to medial transitional cortices, and primary olfactory areas were distinguished by receiving thalamic projections predominantly from neurons in midline and intralaminar nuclei. Notwithstanding some broad differences in the ipsilateral thalamofrontal projections, which appeared to depend on cortical location, the pattern of contralateral projections was thalamus were noted in midline, the magnocellular sector of the mediodorsal nucleus, the anterior medial and intralaminar nuclei, and ranged from 0 to 14% of the ipsilateral; they were directed primarily to olfactory and transitional orbital and medical cortices but rarely projected to eulaminate areas. Several thalamic nuclei projected from both sides to olfactory and transitional areas, but issued only ipsilateral projections to eulaminate areas. Though ipsilateral thalamocortical projections predominate in adult mammalian species, crossed projections are a common feature in development. The results suggest differences in the persistence of contralateral thalamocortical interactions between transitional and eulaminate cortices. © 1994 Wiley-Liss, Inc.     

Regional neocortical thinning in mesial temporal lobe epilepsy

PURPOSE: To determine the nature and extent of regional cortical thinning in patients with mesial temporal lobe epilepsy (MTLE). METHODS: High-resolution volumetric MRIs were obtained on 21 patients with MTLE and 21 controls. Mean cortical thickness was measured within regions of interest and point-by-point across the neocortex using cortical reconstruction and parcellation software. RESULTS: Bilateral thinning was observed within frontal and lateral temporal regions in MTLE patients relative to controls. The most striking finding was bilateral cortical thinning in the precentral gyrus and immediately adjacent paracentral region and pars opercularis of the inferior frontal gyrus, extending to the orbital region. Within the temporal lobe, bilateral thinning was observed in Heschl's gyrus only. Ipsilateral only thinning was observed in the superior and middle temporal gyri, as well as in the medial orbital cortex. Greater asymmetries in cortical thickness were observed in medial temporal cortex in patients relative to controls. Individual subject analyses revealed that this asymmetry reflected significant ipsilateral thinning of medial temporal cortex in 33% of patients, whereas it reflected ipsilateral thickening in 20% of MTLEs. DISCUSSION: Patients with MTLE show widespread, bilateral pathology in neocortical regions that is not appreciated on standard imaging. Future studies are needed that elucidate the clinical implications of neocortical thinning in MTLE.     

New insights in the homotopic and heterotopic connectivity of the frontal portion of the human corpus callosum revealed by microdissection and diffusion tractography

Extensive studies revealed that the human corpus callosum (CC) plays a crucial role in providing large–scale bi‐hemispheric integration of sensory, motor and cognitive processing, especially within the frontal lobe. However, the literature lacks of conclusive data regarding the structural macroscopic connectivity of the frontal CC. In this study, a novel microdissection approach was adopted, to expose the frontal fibers of CC from the dorsum to the lateral cortex in eight hemispheres and in one entire brain. Post‐mortem results were then combined with data from advanced constrained spherical deconvolution in 130 healthy subjects. We demonstrated as the frontal CC provides dense inter‐hemispheric connections. In particular, we found three types of fronto‐callosal fibers, having a dorso‐ventral organization. First, the dorso‐medial CC fibers subserve homotopic connections between the homologous medial cortices of the superior frontal gyrus. Second, the ventro‐lateral CC fibers subserve homotopic connections between lateral frontal cortices, including both the middle frontal gyrus and the inferior frontal gyrus, as well as heterotopic connections between the medial and lateral frontal cortices. Third, the ventro‐striatal CC fibers connect the medial and lateral frontal cortices with the contralateral putamen and caudate nucleus. We also highlighted an intricate crossing of CC fibers with the main association pathways terminating in the lateral regions of the frontal lobes. This combined approach of ex vivo microdissection and in vivo diffusion tractography allowed demonstrating a previously unappreciated three‐dimensional architecture of the anterior frontal CC, thus clarifying the functional role of the CC in mediating the inter‐hemispheric connectivity. Hum Brain Mapp 37:4718–4735, 2016. © 2016 Wiley Periodicals, Inc.     

Topographic organization of medial pulvinar connections with the prefrontal cortex in the rhesus monkey

The medial nucleus of the pulvinar complex (PM) has widespread connections with association cortex. We investigated the connections of the PM with the prefrontal cortex (PFC) in macaque monkeys, with tracers placed into the PM and the PFC, respectively. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) placed into the PM resulted in widespread anterograde terminal labeling in layers III and IV, and retrograde cellular labeling in layer VI of the PFC. Injections of tracers centered on the central/lateral PM resulted in labeling of dorsolateral and orbital regions, whereas injections centered on caudal, medial PM resulted in labeling of dorsomedial and medial PFC. Since injections of the PM included neighboring thalamic nuclei, retrograde tracers were placed into distinct cytoarchitectonic regions of the PFC and retrogradely labeled cells in the posterior thalamus were charted. The results of this series of tracer injections confirmed the results of the thalamic injections. Injections placed into areas 8a, 12 (lateral and orbital), 45, 46 and 11, retrogradely labeled neurons in the central/lateral PM, while tracer injections placed into areas 9, 12 (lateral), 10 and 24, labeled medial PM. The connections of the PM with temporal, parietal, insular, and cingulate cortices were also examined. The central/lateral PM has reciprocal connections with posterior parietal areas 7a, 7ip, and 7b, insular cortex, caudal superior temporal sulcus (STS), caudal superior temporal gyrus (STG), and posterior cingulate, whereas medial PM is connected mainly with the anterior STS and STG, as well as the cingulate cortex and the amygdala. These connectional studies suggest that the central/lateral and medial PM have divergent connections which may be the substrate for distinct functional circuits. J. Comp. Neurol. 379:313–332, 1997. © 1997 Wiley-Liss, Inc.     

Corticolimbic gray matter loss in Parkinson’s disease without dementia

Background: The relationship between corticolimbic involvement and cognitive dysfunction in non‐demented Parkinson’s disease (PD) patients has not yet been elucidated. Objectives: To delineate involvement of the cerebral cortex and limbic structures in non‐demented PD and to clarify distributional differences of gray matter loss between non‐demented PD with impaired cognition (PD‐CI) and without cognitive impairment (PD‐NC). Methods: Operational criteria based on the Clinical Dementia Rating were used to identify PD‐CI. Of 40 consecutive non‐demented patients with PD, 13 were classified as PD‐CI and 27 as PD‐NC. Comparisons of regional gray matter volume (rGMV) were made amongst the PD‐CI, PD‐NC, and control groups using voxel‐based morphometry. Results: Gray matter loss was found extensively in the frontal, temporal, parietal, and occipital cortices in the present non‐demented patients with PD. rGMV in the medial frontal and medial occipital cortices was reduced comparably in the PD‐NC and PD‐CI groups. The severity of gray matter loss in the perisylvian cortices increased in order from the control, to the PD‐NC, to the PD‐CI groups. rGMV reduction in the lateral and orbital frontal, medial and lateral temporal, medial and lateral parietal, and lateral occipital cortices and cerebellum was found specifically in PD‐CI. Conclusions: Our results suggest that corticolimbic degeneration occurs in non‐demented patients with PD, and extensive involvement of the limbic and posterior cortical regions as well as the frontal cortices is associated with cognitive impairment in PD.     

Auditory belt and parabelt projections to the prefrontal cortex in the Rhesus monkey

Recent anatomical and electrophysiological studies have expanded our knowledge of the auditory cortical system in primates and have described its organization as a series of concentric circles with a central or primary auditory core, surrounded by a lateral and medial belt of secondary auditory cortex with a tertiary parabelt cortex just lateral to this belt. Because recent studies have shown that rostral and caudal belt and parabelt cortices have distinct patterns of connections and acoustic responsivity, we hypothesized that these divergent auditory regions might have distinct targets in the frontal lobe. We, therefore, placed discrete injections of wheat germ agglutinin-horseradish peroxidase or fluorescent retrograde tracers into the prefrontal cortex of macaque monkeys and analyzed the anterograde and retrograde labeling in the aforementioned auditory areas. Injections that included rostral and orbital prefrontal areas (10, 46 rostral, 12) labeled the rostral belt and parabelt most heavily, whereas injections including the caudal principal sulcus (area 46), periarcuate cortex (area 8a), and ventrolateral prefrontal cortex (area12vl) labeled the caudal belt and parabelt. Projections originating in the parabelt cortex were denser than those arising from the lateral or medial belt cortices in most cases. In addition, the anterior third of the superior temporal gyrus and the dorsal bank of the superior temporal sulcus were also labeled after prefrontal injections, confirming previous studies. The present topographical results suggest that acoustic information diverges into separate streams that target distinct rostral and caudal domains of the prefrontal cortex, which may serve different acoustic functions. J. Comp. Neurol. 403:141–157, 1999. © 1999 Wiley-Liss, Inc.     

Anatomic organization of basoventral and mediodorsal visual recipient prefrontal regions in the rhesus monkey

The sources of ipsilateral cortical afferent projections to basoventral and mediodorsal prefrontal cortices that receive some visual input were studied with retrograde tracers (horseradish peroxidase or fluorescent dyes) in eight rhesus monkeys. The basoventral regions injected with tracers included basal (orbital) areas 11 and 12, lateral area 12, and ventral area 46. The mediodorsal regions included portions of medial area 32 and the caudal part of dorsal area 8. These sites represent areas within basoventral and mediodorsal prefrontal cortices that show a gradual increase in architectonic differentiation in a direction from the least differentiated orbital and medial limbic cortices toward the most differentiated cortices in the arcuate concavity. The results showed that the visual input to basoventral and mediodorsal prefrontal cortices originated largely in topographically distinct visual areas. Thus, basoventral sites received most of their visual cortical projections from the inferior temporal cortex. The rostral inferior temporal region was the predominant source of visual projections to orbital prefrontal sites, whereas lateral area 12 and ventral area 46 also received projections which were found more caudally. In contrast, mediodorsal prefrontal sites received most of their visual projections from dorsolateral and dorsomedial visual areas. The cells of origin were located in rostromedial visual cortices after injection of retrograde tracers in area 32 and in more caudal medial and dorsolateral visual areas after injection in caudal area 8. The latter also received substantial projections from visuomotor regions in the caudal portion of the lateral bank of the intraparietal sulcus. These results suggest that the basoventral prefrontal cortices are connected with ventral visual areas implicated in pattern recognition and discrimination, whereas the mediodorsal cortices are connected with medial and dorsolateral occipital and parietal areas associated with visuospatial functions. In addition, the prefrontal areas studied received projections from auditory and/or somatosensory cortices, from areas associated with more than one modality, and from limbic regions. Orbital area 12 seemed to be a major target of projections from somatosensory cortices and the rostral portion of medial area 32 received substantial projections from auditory cortices. The least architectonically differentiated areas (orbital area 11 and medial area 32) had more widespread corticocortical connections, including strong links with limbic cortices.(ABSTRACT TRUNCATED AT 400 WORDS)     

Afferent and efferent connections of the dorsolateral precentral gyrus (area 4, hand/arm region) in the macaque monkey, with comparisons to area 8

The afferent and efferent connections of the dorsolateral precentral gyrus, the primary motor cortex for control of the upper extremity, were studied by using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique in three adult macaque monkeys that had received HRP gel implants in this cortical region. Reciprocal corticocortical connections were observed primarily with the supplementary motor area (SMA) in medial premotor area 6 and dorsal bank of the cingulate sulcus, postarcuate area 6 cortex, dorsal cingulate cortex (area 24), superior parietal lobule (area 5, PE/PEa), and inferior parietal lobule (area 7b, PF/PFop, including the secondary somatosensory SII region). In these heavily labeled regions, the associational intrahemispheric afferents originated primarily from small and medium sized pyramidal cells in layer III, but also from layer V. The SMA projections were columnar in organization. Intrahemispheric afferents from contralateral homologous and nonhomologous frontal and cingulate cortices also originated predominantly from layer III, but the connections from contralateral area 4 were almost exclusively from layer III. The bilateral connections with premotor frontal area 6 and cingulate cortices were not observed with parietal regions; i.e., only ipsilateral intrahemispheric parietal corticocortical connections were observed. There were no significant connections with prearcuate area 8 or the granular frontal (prefrontal) cortex. Subcortical afferents originated primarily from the nucleus basalis of Meynert, dorsal claustrum, ventral lateral (VLo and VLc), area X, ventral posterolateral pars oralis (VPLo), central lateral and centromedian thalamic nuclei, lateral hypothalamus, pedunculopontine nucleus, locus ceruleus and subceruleus, and superior central and dorsal raphe nuclei. Lesser numbers of retrogradely labeled neurons were observed in the nucleus of the diagonal band, mediodorsal (MD), paracentral, and central superior lateral thalamic nuclei, nucleus limitans, nucleus annularis, and the mesencephalic and pontine reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Organization of connections between the amygdaloid complex and the perirhinal and parahippocampal cortices in macaque monkeys

Neuroanatomical studies in macaque monkeys have demonstrated that the perirhinal and parahippocampal (PRPH) cortices are strongly interconnected with the hippocampal formation. Recent behavioral evidence indicates that these cortical regions are importantly involved in normal recognition memory function. The PRPH cortices are also interconnected with the amygdaloid complex, although comparatively little is known about the precise topography of these connections. We investigated the topographic organization of reciprocal connections between the amygdala and the PRPH cortices by placing anterograde and retrograde tracers throughout these three regions. We found that there was an organized arrangement of connections between the amygdala and the PRPH cortices and that the deep (lateral, basal, and accessory basal) nuclei of the amygdaloid complex were the source of most connections between the amygdala and the PRPH cortices. The temporal polar regions of the perirhinal cortex had the strongest and most widespread interconnections with the amygdala. Connections from more caudal levels of the perirhinal cortex had a more discrete pattern of termination. Perirhinal inputs to the amygdala terminated primarily in the lateral nucleus, the magnocellular and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. Return projections originated predominately in the lateral nucleus, the intermediate and parvicellular divisions of the basal nucleus, and the magnocellular division of the accessory basal nucleus. The interconnections between the amygdala and the parahippocampal cortex were substantially less robust than those with the perirhinal cortex and mainly involved the basal nucleus. Area TF was more strongly interconnected with the amygdala than was area TH. Input from the parahippocampal cortex terminated predominantly in the lateral half of the parvicellular division of the basal nucleus but also to a lesser extent in the magnocellular division of the basal nucleus and the lateral nucleus. Return projections originated predominantly in the magnocellular division of the basal nucleus and were directed almost exclusively to area TF. © 1996 Wiley-Liss, Inc.     

Localized Cerebellar Hypometabolism in Patients with Complex Partial Seizures

Summary: Purpose : We sought to determine the cause of cerebellar dysfunction in epilepsy and whether this dysfunction was directly related to seizures.
Methods : Cerebellar metabolism was evaluated in 48 patients with a well-defined region of seizure onset and with corresponding hypometabolism. Regions of interest (ROI) were drawn according to a standardized template. If the ROI/honepileptogenic cortex count rate ratio was outside the 95% confidence interval (CI) of controls, the ROI was defined as abnormal. The ratios from cerebellar hemispheres (defined as ipsi- or contralateral to the seizure onset region), were compared among controls (n = 8); patients who had seizure onsets and corresponding hypometabolism mesially in a temporal lobe (patient group 1, n = 19); patients whose seizures had onset mesially in a temporal lobe but spread rapidly to the ipsilateral frontal lobe and who had hypometabolism both in the affected temporal lobe and frontal lobe (patient group 2, n = 23); and patients who had seizure onsets and corresponding hypometabolism in the frontal lobe (patient group 3, n = 6).
Results : Significant hypometabolism was noted in the contralateral cerebellum of patients in groups 2 and 3 [p = 0.007 and p = 0.008, respectively; two-way analysis of variance (ANOVA)]. In contrast, patients in group 1 tended to have lower values in the ipsilateral cerebellum (p = 0.057).
Conclusions : The observed cerebellar changes are consistent with animal data showing that cerebellar connections to frontal lobes are numerous and crossed, whereas the connections to mesial temporal lobes are less abundant, bilateral, with an ipsilateral predominance. The difference between the two groups of patients with mesial temporal seizures suggests that cerebellar dysfunction in partial epilepsy, at least to a certain extent, is related to mechanisms involved in seizure generation and spread.     

Cortically projecting cells in the periaqueductal gray matter of the rat. A retrograde fluorescent tracer study

The topographical organization of the afferent input from the periaqueductal gray matter (PAG) to the cerebral cortex has been assessed in rats by retrograde transport of the fluorescent tracers Fast blue (FB) and Diamidino yellow (DY). The olfactory, medial frontal (infralimbic, prelimbic and anterior cingulate cortices), lateral frontal (motor), parietal, temporal, occipital and insular cortices were explored by placing two fluorescent tracers into two different cortical regions. The PAG contained the largest number of labeled neurons in medial frontal cortex injections, followed by olfactory and lateral frontal cortices. Fewer retrogradely labeled cells were seen after injections in parietal, temporal occipital and insular cortices. All labeled cells were exclusively located in the medial and lateroventral divisions of the PAG (PAGm and PAGlv). The longitudinal extent of the labeling in PAGm was more extensive than in PAGlv. The labeled neurons in the medial frontal cortex group extended through most of the PAG, while in the remaining groups it was restricted to the caudal one-third of the PAG. Neurons with projections to two different cortical regions were only a small fraction of the total population of labeled cells. Our data indicate that the medial frontal cortex is the most important recipient of a direct PAG input, followed by the lateral frontal cortex. Parietal, temporal, occipital and insular cortices receive only a minor projection. It is concluded that the PAG sends direct projections over the majority of the cortical mantle. Therefore, the possibility arises that the cerebral cortex receives a direct influence from the brainstem without a thalamic relay.     

Afferent connections of the perirhinal cortex in the rat

Connections of the perirhinal cortex in the.rat brain were studied using anterograde (³H-proline/leucine) and retrograde (horseradish peroxidase) tracers. The perirhinal cortex receives major projections from medial precen-tral, anterior cingulate, prelimbic, ventral lateral orbital, ventral and posterior agranular insular, temporal, superior and granular parietal, lateral occipital, agranular retrosplenial, and ectorhinal cortices, and from the pre-subiculum, subiculum, and diagonal band of Broca. Rostral neocortical areas project predominantly to rostral perirhinal regions while more caudal neocortical and subicular areas project predominantly to caudal perirhinal regions. Terminal fields are further segregated within perirhinal cortex to either the dorsal or ventral banks of the rhinal sulcus. All afferents from frontal areas terminate predominantly in the deep layers of its ventral bank; afferents from temporal, parietal, and lateral occipital areas terminate predominantly in the deep and superficial layers along its dorsal bank; and afferents from ectorhinal cortex terminate in a column within its dorsal bank. Cortical cells which project to perirhinal areas are found predominantly in layer II and the superficial part of layer III. However, ventrolateral orbital, parietal, and lateral occipital cortex projections originate predominantly from layer V. Perirhinal areas also receive afferents from the nucleus reuniens of the thalamus, lateral nucleus of the amygdala, claustrum, supramammillary nuclei, and the dorsal raphe nuclei.     

Corticothalamic connections of paralimbic regions in the rhesus monkey

This study addressed the issue of whether paralimbic regions of the cerebral cortex share common thalamic projections. The corticothalamic connections of the paralimbic regions of the orbital frontal, medial prefrontal, cingulate, parahippocampal, and temporal polar cortices were studied with the autoradiographic method in the rhesus monkey. The results revealed that the orbital frontal, medial prefrontal, and temporal polar proisocortices have substantial projections to both the dorsomedial and medial pulvinar nuclei, whereas the anterior cingulate proisocortex (area 24) projects exclusively to the dorsomedial nucleus. These proisocortical areas also have thalamic connections with the intralaminar and midline nuclei. The cortical areas between the proisocortical regions on the one hand and the isocortical areas on the other, that is, the posterior cingulate region (area 23) and the posterior parahippocampal gyrus (areas TF and TH), project predominantly to the dorsal portion of the medial pulvinar nucleus, the anterior nuclear group (AV, AM), and the lateral dorsal (LD) nucleus. Additionally, the posterior cingulate and medial parahippocampal gyri (area TH) have projections to the lateral posterior (LP) nucleus. Thus, it appears that the proisocortical areas, which are characterized by a predominance of infragranular layers and an absence of layer IV, have common thalamic relationships. Likewise, the intermediate paralimbic areas between the proisocortex and isocortical regions, which also have a predominance of infragranular layers but in addition have evidence of a fourth layer, project to the medial pulvinar and to the so-called limbic nuclei, AV, AM, LD, as well as a modality-specific nucleus, LP.     

Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey

The origin and termination of axonal connections between the orbital and medial prefrontal cortex (OMPFC) and the temporal, insular, and opercular cortex have been analyzed with anterograde and retrograde axonal tracers, injected in the OMPFC or temporal cortex. The results show that there are two distinct, complementary, and reciprocal neural systems, related to the previously defined "orbital" and "medial" prefrontal networks. The orbital prefrontal network, which includes areas in the central and lateral part of the orbital cortex, is connected with vision-related areas in the inferior temporal cortex (especially area TEav) and the fundus and ventral bank of the superior temporal sulcus (STSf/v), and with somatic sensory-related areas in the frontal operculum (OPf) and dysgranular insular area (Id). No connections were found between the orbital network and auditory areas. The orbital network is also connected with taste and olfactory cortical areas and the perirhinal cortex and appears to be involved in assessment of sensory objects, especially food. The medial prefrontal network includes areas on the medial surface of the frontal lobe, medial orbital areas, and two caudolateral orbital areas. It is connected with the rostral superior temporal gyrus (STGr) and the dorsal bank of the superior temporal sulcus (STSd). This region is rostral to the auditory parabelt areas, and there are only relatively light connections between the auditory areas and the medial network. This system, which is also connected with the entorhinal, parahippocampal, and cingulate/retrosplenial cortex, may be involved in emotion and other self-referential processes.     

Entorhinal cortex of the rat: Cytoarchitectonic subdivisions and the origin and distribution of cortical efferents

The origins and terminations of entorhinal cortical projections in the rat were analyzed in detail with retrograde and anterograde tracing techniques. Retrograde fluorescent tracers were injected in different portions of olfactory, medial frontal (infralimbic and prelimbic areas), lateral frontal (motor area), temporal (auditory), parietal (somatosensory), occipital (visual), cingulate, retrosplenial, insular, and perirhinal cortices. Anterograde tracer injections were placed in various parts of the rat entorhinal cortex to demonstrate the laminar and topographical distribution of the cortical projections of the entorhinal cortex. The retrograde experiments showed that each cortical area explored receives projections from a specific set of entorhinal neurons, limited in number and distribution. By far the most extensive entorhinal projection was directed to the perirhinal cortex. This projection, which arises from all layers, originates throughout the entorhinal cortex, although its major origin is from the more lateral and caudal parts of the entorhinal cortex. Projections to the medial frontal cortex and olfactory structures originate largely in layers II and III of much of the intermediate and medial portions of the entorhinal cortex, although a modest component arises from neurons in layer V of the more caudal parts of the entorhinal cortex. Neurons in layer V of an extremely laterally located strip of entorhinal cortex, positioned along the rhinal fissure, give rise to the projections to lateral frontal (motor), parietal (somatosensory), temporal (auditory), occipital (visual), anterior insular, and cingulate cortices. Neurons in layer V of the most caudal part of the entorhinal cortex originate projections to the retrosplenial cortex. The anterograde experiments confirmed these findings and showed that in general, the terminal fields of the entorhinal-cortical projections were densest in layers I, II, and III, although particularly in the more densely innervated areas, labeling in layer V was also present. Comparably distributed, but much weaker projections reach the contralateral hemisphere. Our results show that in the rat, hippocampal output can reach widespread portions of the neocortex through a relay in a very restricted part of the entorhinal cortex. However, most of the hippocampal-cortical connections will be mediated by way of entorhinal-perirhinal-cortical connections. We conclude that, in contrast to previous notions, the overall organization of the hippocampal-cortical connectivity in the rat is largely comparable to that in the monkey. Hippocampus 7:146–183, 1997. © 1997 Wiley-Liss, Inc.     

Ipsilateral and contralateral MRI volumetric abnormalities in chronic unilateral temporal lobe epilepsy and their clinical correlates

PURPOSE: To assess the presence, extent, and clinical correlates of quantitative MR volumetric abnormalities in ipsilateral and contralateral hippocampus, and temporal and extratemporal lobe regions in unilateral temporal lobe epilepsy (TLE). METHODS: In total, 34 subjects with unilateral left (n = 15) or right (n = 19) TLE were compared with 65 healthy controls. Regions of interest included the ipsilateral and contralateral hippocampus as well as temporal, frontal, parietal, and occipital lobe gray and white matter. Clinical markers of neurodevelopmental insult (initial precipitating insult, early age of recurrent seizures) and chronicity of epilepsy (epilepsy duration, estimated number of lifetime generalized seizures) were related to magnetic resonance (MR) volume abnormalities. RESULTS: Quantitative MR abnormalities extend beyond the ipsilateral hippocampus and temporal lobe with extratemporal (frontal and parietal lobe) reductions in cerebral white matter, especially ipsilateral but also contralateral to the side of seizure onset. Volumetric abnormalities in ipsilateral hippocampus and bilateral cerebral white matter are associated with factors related to both the onset and the chronicity of the patients' epilepsy. CONCLUSIONS: These cross-sectional findings support the view that volumetric abnormalities in chronic TLE are associated with a combination of neurodevelopmental and progressive effects, characterized by a prominent disruption in ipsilateral hippocampus and neural connectivity (i.e., white matter volume loss) that extends beyond the temporal lobe, affecting both ipsilateral and contralateral hemispheres.     

Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior

Common efferent projections of the dorsolateral prefrontal cortex and posterior parietal cortex were examined in 3 rhesus monkeys by placing injections of tritiated amino acids and HRP in frontal and parietal cortices, respectively, of the same hemisphere. Terminal labeling originating from both frontal and parietal injection sites was found to be in apposition in 15 ipsilateral cortical areas: the supplementary motor cortex, the dorsal premotor cortex, the ventral premotor cortex, the anterior arcuate cortex (including the frontal eye fields), the orbitofrontal cortex, the anterior and posterior cingulate cortices, the frontoparietal operculum, the insular cortex, the medial parietal cortex, the superior temporal cortex, the parahippocampal gyrus, the presubiculum, the caudomedial lobule, and the medial prestriate cortex. Convergent terminal labeling was observed in the contralateral hemisphere as well, most prominently in the principal sulcal cortex, the superior arcuate cortex, and the superior temporal cortex. In certain common target areas, as for example the cingulate cortices, frontal and parietal efferents terminate in an array of interdigitating columns, an arrangement much like that observed for callosal and associational projections to the principal sulcus (Goldman-Rakic and Schwartz, 1982). In other areas, frontal and parietal terminals exhibit a laminar complementarity: in the depths of the superior temporal sulcus, prefrontal terminals are densely distributed within laminae I, III, and V, whereas parietal terminals occupy mainly laminae IV and VI directly below the prefrontal bands. Subcortical structures also receive apposing or overlapping projections from both prefrontal and parietal cortices. The dorsolateral prefrontal and posterior parietal cortices project to adjacent, longitudinal domains of the neostriatum, as has been described previously (Selemon and Goldman-Rakic, 1985); these projections are also found in close apposition in the claustrum, the amygdala, the caudomedial lobule, and throughout the anterior medial, medial dorsal, lateral dorsal, and medial pulvinar nuclei of the thalamus. In the brain stem, both areas of association cortex project to the intermediate layers of the superior colliculus and to the midline reticular formation of the pons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cortical and thalamic connections of the representations of the teeth and tongue in somatosensory cortex of new world monkeys

Connections of representations of the teeth and tongue in primary somatosensory cortex (area 3b) and adjoining cortex were revealed in owl, squirrel, and marmoset monkeys with injections of fluorescent tracers. Injection sites were identified by microelectrode recordings from neurons responsive to touch on the teeth or tongue. Patterns of cortical label were related to myeloarchitecture in sections cut parallel to the surface of flattened cortex, and to coronal sections of the thalamus processed for cytochrome oxidase (CO). Cortical sections revealed a caudorostral series of myelin dense ovals (O1-O4) in area 3b that represent the periodontal receptors of the contralateral teeth, the contralateral tongue, the ipsilateral teeth, and the ipsilateral tongue. The ventroposterior medial subnucleus, VPM, and the ventroposterior medial parvicellular nucleus for taste, VPMpc, were identified in the thalamic sections. Injections placed in the O1 oval representing teeth labeled neurons in VPM, while injections in O2 representing the tongue labeled neurons in both VPMpc and VPM. These injections also labeled adjacent part of areas 3a and 1, and locations in the lateral sulcus and frontal lobe. Callosally, connections of the ovals were most dense with corresponding ovals. Injections in the area 1 representation of the tongue labeled neurons in VPMpc and VPM, and ipsilateral area 3b ovals, area 3a, opercular cortex, and cortex in the lateral sulcus. Contralaterally, labeled neurons were mostly in area 1. The results implicate portions of areas 3b, 3a, and 1 in the processing of tactile information from the teeth and tongue, and possibly taste information from the tongue.     

Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey

Prefrontal cortices have been implicated in autonomic function, but their role in this activity is not well understood. Orbital and medial prefrontal cortices receive input from cortical and subcortical structures associated with emotions. Thus, the prefrontal cortex may be an essential link for autonomic responses driven by emotions. Classic studies have demonstrated the existence of projections between prefrontal cortex and the hypothalamus, a central autonomic structure, but the topographic organization of these connections in the monkey has not been clearly established. We investigated the organization of bidirectional connections between these areas in the rhesus monkey by using tracer injections in orbital, medial, and lateral prefrontal areas. All prefrontal areas investigated received projections from the hypothalamus, originating mainly in the posterior hypothalamus. Differences in the topography of hypothalamic projection neurons were related to both the location and type of the target cortical area. Injections in lateral eulaminate prefrontal areas primarily labeled neurons in the posterior hypothalamus that were equally distributed in the lateral and medial hypothalamus. In contrast, injections in orbitofrontal and medial limbic cortices labeled neurons in the anterior and tuberal regions of the hypothalamus and in the posterior region. Projection neurons targeting orbital limbic cortices were more prevalent in the lateral part of the hypothalamus, whereas those targeting medial limbic cortices were more prevalent in the medial hypothalamus. In comparison to the ascending projections, descending projections from prefrontal cortex to the hypothalamus were highly specific, originating mostly from orbital and medial prefrontal cortices. The ascending and descending connections overlapped in the hypothalamus in areas that have autonomic functions. These results suggest that specific orbitofrontal and medial prefrontal areas exert a direct influence on the hypothalamus and may be important for the autonomic responses evoked by complex emotional situations. J. Comp. Neurol. 398:393–419, 1998. © 1998 Wiley-Liss, Inc.     

Insula of the old world monkey. II: Afferent cortical input and comments on the claustrum

The afferent connections of the insula in the rhesus monkey were studied with axonal transport methods. Injections of horseradish peroxidase (HRP) in the insula revealed labeled neurons in the prefrontal cortex, the lateral orbital region, the frontopariefal operculum, the cingulate gyrus and adjacent medial cortex, the prepiriforrn olfactory cortex, the temporal pole, the cortex of the superior temporal sulcus, the rhinal cortex, the supratem-poral plane, and the posterior parietal lobe. Tritiated amino acid (TAA) injections in some of the cortical regions which contained retrogradely labeled neurons confirmed projections to the insula from prefrontal granular cortex, orbital frontal cortex, prepiriform cortex, temporal pole, rhinal cortex, cingulate gyrus, frontal operculum, and parietal cortex. In these studies, cortical areas that projected to the insula also projected to the claustrum. However, the topographic and quantitative relationships between the projections into the insula and those into the claustrum were inconsistent. Moreover, the claustrum has additional connections which it does not share with the insula. A selected review of the literature suggests that the claustrum and insula differ widely also with respect to ontogenesis and functional specialization.