Mapping temporo-parietal and temporo-occipital cortico-cortical connections of the human middle longitudinal fascicle in subject-specific, probabilistic, and stereotaxic Talairach spaces.

Originally, the middle longitudinal fascicle (MdLF) was defined as a long association fiber tract connecting the superior temporal gyrus and temporal pole with the angular gyrus. More recently its description has been expanded to include all long postrolandic cortico-cortical association connections of the superior temporal gyrus and dorsal temporal pole with the parietal and occipital lobes. Despite its location and size, which makes MdLF one of the most prominent cerebral association fiber tracts, its discovery in humans is recent. Given the absence of a gold standard in humans for this fiber tract, its precise and complete connectivity remains to be determined with certainty. In this study using high angular resolution diffusion MRI (HARDI), we delineated for the first time, six major fiber connections of the human MdLF, four of which are temporo-parietal and two temporo-occipital, by examining morphology, topography, cortical connections, biophysical measures, volume and length in seventy brains. Considering the cortical affiliations of the different connections of MdLF we suggested that this fiber tract may be related to language, attention and integrative higher level visual and auditory processing associated functions. Furthermore, given the extensive connectivity provided to superior temporal gyrus and temporal pole with the parietal and occipital lobes, MdLF may be involved in several neurological and psychiatric conditions such as primary progressive aphasia and other aphasic syndromes, some forms of behavioral variant of frontotemporal dementia, atypical forms of Alzheimer's disease, corticobasal degeneration, schizophrenia as well as attention-deficit/hyperactivity Disorder and neglect disorders.

Striatal connections of the parietal association cortices in rhesus monkeys.

The corticostriatal connections of the parietal association cortices were examined by the autoradiographic technique in rhesus monkeys. The results show that the rostral portion of the superior parietal lobule projects predominantly to the dorsal portion of the putamen, whereas the caudal portion of the superior parietal lobule and the cortex of the upper bank of the intraparietal sulcus have connections with the caudate nucleus as well as with the dorsal portion of the putamen. The medial parietal convexity cortex projects strongly to the caudate nucleus, and has less extensive projections to the putamen. In contrast, the medial parietal cortex within the caudal portion of the cingulate sulcus projects predominantly to the dorsal portion of the putamen, and has only minor connections with the caudate nucleus. The rostral portion of the inferior parietal lobule projects mainly to the ventral sector of the putamen, and has only minor connections with the caudate nucleus. The middle portion of the inferior parietal lobule has sizable projections to both the putamen and the caudate nucleus. The caudal portion of the inferior parietal lobule as well as the lower bank of the intraparietal sulcus project predominantly to the caudate nucleus, and have relatively minor connections with the putamen. The cortex of the parietal opercular region also shows a specific pattern of corticostriatal projections. Whereas the rostral portion projects exclusively to the ventral sector of the putamen, the caudal portion has connections to the caudate nucleus as well. Thus, it seems that parietostriatal projections show a differential topographic distribution; within both the superior and the inferior parietal region, as one progresses from rostral to caudal, there is a corresponding shift in the predominance of projections from the putamen to the caudate nucleus. In addition, with regard to the projections to the putamen, the superior parietal lobule is related mainly to the dorsal portion, and the inferior parietal lobule to the ventral portion. The striatal projections of the cortex of the caudal portion of the cingulate gyrus (corresponding in part to the supplementary sensory area) and of the rostral parietal opercular region (corresponding in part to the second somatosensory area) are directed almost exclusively to the dorsal and ventral sectors of the putamen, respectively. This pattern resembles that of the primary somatosensory cortex. The results are discussed with regard to the overall architectonic organization of the posterior parietal region. Possible functional aspects of parietostriatal connectivity are considered in the light of physiological and behavioral studies.

Corticostriatal connections of extrastriate visual areas in rhesus monkeys.

The striatal connections of extrastriate visual areas were examined by the autoradiographic technique in rhesus monkeys. The medial as well as the dorsolateral extrastriate regions project preferentially to dorsal and lateral portions of the head and of the body of the caudate nucleus, as well as to the caudodorsal sector of the putamen. The rostral portion of the annectant gyrus has connections to the caudal sector of the body and to the genu, whereas projections from the caudal portion of the lower bank of the superior temporal sulcus are directed to dorsal and central sectors of the head and the body, to the genu and the tail, as well as to the caudal putamen. The ventrolateral extrastriate region is related mainly to the ventral sector of the body, to the genu and the tail, and to the caudal putamen. In contrast, the striatal projections of the ventromedial extrastriate cortex resemble those of the medial and dorsolateral regions. The caudal inferotemporal cortex is related strongly to the tail of the caudate nucleus and to the ventral putamen. The differential corticostriatal connectivity of the various extrastriate regions may contribute to the specific functional roles of these cortices. Thus, the connections from the dorsomedial, dorsolateral, and ventromedial areas to dorsal portions of the caudate nucleus and of the putamen may serve a visuospatial function. In contrast, the connections from the ventrolateral extrastriate and inferotemporal regions to the tail of the caudate nucleus and to the ventral putamen may have a role in visual object-related processes.

Prefrontostriatal connections in relation to cortical architectonic organization in rhesus monkeys.

Prefrontostriatal connections were investigated in rhesus monkeys using the autoradiographic technique to examine whether there are systematic relationships with regard to the architectonic organization of the prefrontal cortex. On the basis of progressive laminar elaboration, the different regions of the prefrontal cortex can be grouped into two architectonic trends. The dorsal trend, which begins in the medial proisocortical areas, can be followed through the dorsolateral prefrontal cortex, culminating in the dorsal arcuate region. The ventral trend, which originates in the orbital proisocortex, can be traced through the inferior prefrontal convexity to the ventral arcuate region. The results show that the main connections from the prefrontal cortex to the striatum are to the head and body of the caudate nucleus. These connections are topographically organized. Medial and dorsal prefrontal areas project predominantly to the dorsal and central portion of the head and body of the caudate nucleus, whereas orbital and inferior prefrontal areas are related mainly to the ventral and central portion. Moreover, prefrontostriatal connections have a medial-lateral topography. Medial and orbital prefrontal areas project medially in the head and body of the caudate nucleus, whereas the dorsal and ventral arcuate regions project laterally, adjacent to the internal capsule. The prefrontal regions above and below the principal sulcus project mainly to the intermediate sector of the head and body of the nucleus. However, there appears to be some degree of overlap of corticostriatal projections from the dorsal and ventral prefrontal regions, as well as within each trend. Relatively minor projections are directed to the putamen as well as to the tail of the caudate nucleus from certain subregions of the prefrontal cortex. Thus the distribution of prefrontostriatal connections seems to reflect the architectonic organization of the prefrontal cortex. Possible functional aspects of prefrontostriatal connectivity are considered in the light of behavioral and physiological studies.

Corticothalamic connections of extrastriate visual areas in rhesus monkeys.

Corticothalamic connections of extrastriate visual areas were studied by using the autoradiographic anterograde tracing technique. The results show that the medial extrastriate region above the calcarine sulcus projects mainly to the lateral pulvinar (PL), medial pulvinar (PM), and lateral posterior (LP) nuclei. In addition, the dorsal portion of the medial region has connections to the lateral dorsal (LD) as well as to intralaminar nuclei. The dorsolateral extrastriate region projects strongly to the PL and LP nuclei, to the PM and inferior pulvinar (PI) nuclei, and to the LD and intralaminar nuclei. The lateral extrastriate region above the inferior occipital sulcus (IOS) has strong connections to both the PL and PI nuclei and has minor projections to the PM and oral pulvinar nuclei. The ventrolateral extrastriate region below the IOS projects mainly to the PI nucleus and to the caudal portion of the PL nucleus and has some projections to the PM nucleus. The ventromedial extrastriate region medial to the occipitotemporal sulcus has strong connections with the ventral and medial sectors of the PI nucleus. This region also projects to the caudal portion of the PL nucleus and has minor connections to the LP nucleus. Finally, the annectant gyrus projects to the PL nucleus and to the rostral portion of the PI nucleus and has minor connections to the PM nucleus. Thus, the medial and dorsolateral extrastriate regions are related mainly to the PL and LP nuclei as well as to intralaminar nuclei. In contrast, the ventrolateral and ventromedial regions are connected strongly with the PI nucleus. This connectional organization appears to reflect functional differentiation at the cortical level.

Corticothalamic connections of the posterior parietal cortex in the rhesus monkey.

Corticothalamic connections of posterior parietal regions were studied in the rhesus monkey by using the autoradiographic technique. Our observations indicate that the rostral superior parietal lobule (SPL) is connected with the ventroposterolateral (VPL) thalamic nucleus. In addition, whereas the rostral SPL is connected with the ventrolateral (VL) and lateral posterior (LP) thalamic nuclei, the rostral IPL has connections with the ventroposteroinferior (VPI), ventroposteromedial parvicellular (VPMpc), and suprageniculate (SG) nuclei as well as the VL nucleus. The caudal SPL and the midportion of IPL show projections mainly to the lateral posterior (LP) and oral pulvinar (PO) nuclei, respectively. These areas also have minor projections to the medial pulvinar (PM) nucleus. Finally, the medial SPL and the caudal IPL project heavily to the PM nucleus, dorsally and ventrally, respectively. In addition, the medial SPL has some connections with the LP nucleus, whereas the caudal IPL has projections to the lateral dorsal (LD) nucleus. Furthermore, the caudal and medial SPL and the caudal IPL regions have additional projections to the reticular and intralaminar nuclei-the caudal SPL predominantly to the reticular, and the caudal IPL mainly to the intralaminar nuclei. These results indicate that the rostral-to-caudal flow of cortical connectivity within the superior and inferior parietal lobules is paralleled by a rostral-to-caudal progression of thalamic connectivity. That is, rostral parietal association cortices project primarily to modality-specific thalamic nuclei, whereas more caudal regions project most strongly to associative thalamic nuclei.

Thalamic connections of the cortex of the superior temporal sulcus in the rhesus monkey.

The thalamocortical connections of the superior temporal sulcus (STS) were studied by means of the WGA-HRP retrograde tracing technique. The results indicate that the distribution of thalamic projections varies along the rostral-caudal dimension of the STS. Thus the rostral portion of the upper bank receives input primarily from the medialmost portion of the medial pulvinar (PM) nucleus. The middle region of the upper bank receives projections from medial and central portions of the PM nucleus, and also from the oral pulvinar, limitans, suprageniculate, medial geniculate, and dorsomedial nuclei. The cortex of the caudal portion of the upper bank has basically similar thalamic input; however, the projections from the PM nucleus originate in central and lateral portions. Additionally, there are projections from the lateral pulvinar (PL), ventroposterolateral, central lateral, parafascicular, and paracentral nuclei. In contrast to the dorsal bank, the cortex of the ventral bank of the STS receives somewhat different and less extensive thalamic input. The rostral portion of the lower bank receives projections only from the ventromedial sector of the PM nucleus, whereas the middle portion of the lower bank receives projections from the PL and the inferior pulvinar nuclei as well as from the PM nucleus. The upper bank of the STS, on the basis of physiological and anatomical studies (Jones and Powell, '70; Seltzer and Pandya, '78; Gross et al., '81; Baylis et al., '87), has been shown to contain multimodal areas. The present data indicate that the multimodal region of the STS has a preferential relationship with the central sector of the PM nucleus.

Corticostriatal connections of the superior temporal region in rhesus monkeys.

Corticostriatal connections of auditory areas within the supratemporal plane and in rostral and caudal portions of the superior temporal gyrus were studied by the autoradiographic anterograde tracing technique. The results show that the primary auditory cortex has limited projections to the caudoventral putamen and to the tail of the caudate nucleus. In contrast, the second auditory area within the circular sulcus has connections to the rostral and the caudal putamen and to the body of the caudate nucleus and the tail. The association areas of the superior temporal gyrus collectively have widespread corticostriatal projections characterized by differential topographic distributions. The rostral part of the gyrus projects to ventral portions of the head of the caudate nucleus and of the body and to the tail. In addition, there are connections to rostroventral and caudoventral portions of the putamen. The mid-portion of the gyrus projects to similar striatal regions, but the connections to the head of the caudate nucleus are less extensive. Compared with the rostral and middle parts of the superior temporal gyrus, the caudal portion has little connectivity to the tail of the caudate nucleus. It projects more dorsally within the head and the body and also more dorsally within the caudal putamen. These differential patterns of corticostriatal connectivity are consistent with functional specialization at the cortical level.

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.

Widespread corticostriate projections from temporal cortex of the rhesus monkey.

The corticostriate projections of temporal areas TA, TE, TF, TG, 35, and 28 were studied in the rhesus monkey with the use of autoradiography. Widespread projections were observed to rostral as well as caudal parts of the striatum for all areas except area 28. For example, areas TA and TG have sizable projections to the medial or periventricular part of the head of the caudate nucleus, as well as to the medial part of the tail of this structure and the dorsally adjacent putamen. Areas TE and TF also were observed to send strong projections to the head of the caudate nucleus. In addition, they project to the rostral putamen. Both have projections to the tail of the caudate nucleus and caudal putamen. The widespread distribution of temporostriate axons to the rostral striatum suggests strongly that previous silver impregnation studied have not only underestimated the strength of the temporal cortical contribution to the corticostriate system, but also failed to identify the major projection zone of temporostriate axon terminals. For example, while all temporal cortical areas contribute projections to an organized topography in the tail of the caudate nucleus and the ventrocaudal putamen, they were observed consistently to have larger projections to the head of the caudate nucleus and rostral putamen. These results add to a growing body of evidence which demonstrates the existence of widespread nonmotor cortical input to the basal ganglia, and an organization of this input far greater in complexity than that demonstrated by earlier suppressive silver impregnation methods.

Proposed neural circuitry for spatial memory in the primate brain.

The possible cerebral cortical circuitry for spatial memory in primates is discussed in light of a conceptual model and clinical as well as animal behavioral data. It is proposed that spatial memory formation begins with the arrival of sensory information in primary sensory areas and involves progressive elaboration through parasensory and higher-order association cortices. The connectivity between the association areas and the paralimbic and limbic regions is viewed as critical to the consolidation process. Finally, the execution of spatial behavior is presumed to involve the post-Rolandic and paralimbic projections to the frontal lobe. It is hoped that this conceptualization may provide a framework for further studies dealing with spatial memory.

Cortico-striate projections in the rhesus monkey: the organization of certain cortico-caudate connections.

The organization of cortical projections to the caudate nucleus was investigated in the rhesus monkey, using the autoradiographic tracing method. Following injections of tritiated leucine and proline into selected pre- and post-Rolandic association areas in the frontal, parietal, occipital and temporal lobes, widespread projections were observed to one, or more typically, more than one of the major subdivisions of the caudate nucleus. When cortical areas having strong reciprocal cortico-cortical connections were compared, a considerable communality of their cortico-caudate projections was noted; depending on the location of the cortical areas, the region of common distribution lay within the head, the body, or the tail of the caudate nucleus. This correlation between cortico-cortical and cortico-striate projections characterized all pairs of cases studied. It suggests a previously undescribed principle of organization within the telencephalon, namely, that areas of cerebral cortex having reciprocal cortico-cortical connections, while having unique overall patterns of projection to the caudate nucleus, project, in part, to one and the same region of the nucleus. This might imply that a given region of the caudate nucleus receives input not only from a particular area of cortex, but also from all other cortical areas reciprocally interconnected with that area.

Fiber pathways and cortical connections of preoccipital areas in rhesus monkeys.

An understanding of visual function at the cerebral cortical level requires detailed knowledge of anatomical connectivity. Cortical association pathways and terminations of preoccipital visual areas were investigated in rhesus monkeys by using the autoradiographic tracing technique. Medial and adjacent dorsomedial preoccipital regions project via the occipitofrontal fascicle to the frontal lobe (dorsal area 6, and areas 8Ad, 8B, and 46); via the dorsal portion of the superior longitudinal fascicle (SLF) to dorsal area 6, area 9, and the supplementary motor area; and via the cingulate fascicle to area 24. In addition, medial and dorsomedial preoccipital areas send projections to parietal (areas PGm, PEa, PG-Opt, and POa) and superior temporal (areas MST and MT) regions. In contrast, connections from the dorsolateral, annectant, and ventral preoccipital regions are conveyed via the inferior longitudinal fascicle (ILF) to the parietal lobe (areas POa and IPd), superior temporal sulcus (areas MT, MST, FST, V4t, and IPa), inferotemporal region (areas TEO and TE1-TE3), and parahippocampal gyrus (areas TF, TH, and TL). The central-lateral preoccipital region projects via an ILF-SLF pathway to frontal area 8Av. The preoccipital areas also have caudal connections to occipital areas V1, V2, and V3. Finally, preoccipital regions are interconnected via different intrinsic pathways. These findings provide further insight into the nature of preoccipital fiber pathways and the connectional organization of the visual system.

Corticothalamic connections of the superior temporal sulcus in rhesus monkeys.

The corticothalamic connections of the superior temporal sulcus (STS) were studied by means of the autoradiographic technique. The results indicate that corticothalamic connections of the STS in general reciprocate thalamocortical connections. The cortex of the upper bank of the STS-multimodal areas TPO and PGa-projects to four major thalamic targets: the pulvinar complex, the mediodorsal nucleus, the limitans-suprageniculate nucleus, as well as intralaminar nuclei. Within the pulvinar complex, the main projections of the upper bank of the STS are directed to the medial pulvinar (PM) nucleus. Rostral upper bank regions tend to project caudally and medially within the PM nucleus, caudal upper bank regions, more laterally and ventrally. The mid-portion of the upper bank tends to occupy the central sector of the PM nucleus. There are also relatively minor projections from upper bank regions to the lateral pulvinar (PL) and oral pulvinar (PO) nuclei. In contrast to the upper bank, the projections from the lower bank are directed primarily to the pulvinar complex, with only minor projections to intralaminar nuclei. The rostral portion of the lower bank projects mainly to caudal and medial regions of the PM nucleus, whereas the caudal lower bank projects predominantly to the lateral PM nucleus, and also to the PL, PO, and inferior pulvinar (PI) nuclei. The mid-portion of the lower bank projects mainly to central and lateral portions of the PM nucleus, and also to the PI and PL nuclei. The rostral depth of the STS projects mainly to the PM nucleus, with only minor connections to the PO, PI, and PL nuclei. The mid-portion of multimodal area TPO of the upper bank, areas TPO2 and TPO3, projects preferentially to the central sector of the PM nucleus. It is possible that this STS-thalamic connectivity has a role in behavior that is dependent upon more than one sensory modality.

Laminar origin of striatal and thalamic projections of the prefrontal cortex in rhesus monkeys.

Prefrontostriatal and prefrontothalamic connections in rhesus monkeys have been shown to be organized in a topographic manner. These projections originate largely from infragranular layers V and VI. To examine whether the striatal and thalamic connections from the prefrontal cortex arise from separate neuronal populations or are collateralized, two different fluorescent retrograde tracers (diamidino yellow and fast blue) were injected into topographically similar regions of the head of the caudate nucleus and the mediodorsal nucleus in the same animal. The results show that although prefrontostriatal and prefrontothalamic projections arise from similar topographic regions, their laminar origins are distinctive. The connections to the head of the caudate nucleus originate mainly from layer Va, to a lesser extent from layer Vb, with a minor contribution from layers III and VI. In contrast, the projections to the mediodorsal nucleus emanate largely from layer VI, and also from layer Vb. Only occasional double-labeled neurons were observed, indicating that prefrontostriatal and prefrontothalamic connections originate from separate neuronal populations. The differential laminar distributions of neurons projecting to the head of the caudate nucleus and the mediodorsal nucleus suggest that these structures may receive independent types of information from the prefrontal cortex.

Comparison of prefrontal architecture and connections.

The advent of new technology has led to a proliferation of studies examining the functional roles of discrete prefrontal cortical areas. This has created a need for more precise information regarding the morphological characteristics of this region. Existing architectonic maps of human and monkey brains are not compatible with regard to areal delineations and topography, creating significant difficulty in interpreting comparative data. Therefore, we have re-examined the comparative morphological organization of the prefrontal cortex in humans and rhesus monkeys. Our analysis indicates that the architectonic areas in both species correspond in terms of morphological features as well as topographical locations. We have developed a common organizational schema for these areas, thereby allowing for a resolution of previous discrepancies. Moreover, in monkeys a connectional analysis has revealed that each of the newly designated areas is characterized by a unique pattern of cortical relationships. The present organizational schema provides a framework for interrelating findings such as those obtained from human brain imaging studies with those from behavioural investigations of non-human primates.

MRI-Based topographic parcellation of human cerebral white matter and nuclei II. Rationale and applications with systematics of cerebral connectivity.

We describe a system for parcellation of the human cerebral white matter and nuclei, based upon magnetic resonance images. An algorithm for subdivision of the cerebral central white matter according to topographic criteria is developed in the companion manuscript. In the present paper we provide a rationale for this system of parcellation of the central white matter and we extend the system of cerebral parcellation to include principal subcortical gray structures such as the thalamus and the basal ganglia. The volumetric measures of the subcortical gray and white matter parcellation units in 20 young adult brains are computed and reported here as well. In addition, with the comprehensive system for cerebral gray and white matter structure parcellation as reference, we formulate a systematics of forebrain connectivity. The degree to which functionally specific brain areas correspond to topographically specific areas is an open empirical issue. The resolution of this issue requires the development of topographically specific anatomic analyses, such as presented in the current system, and the application of such systems to a comprehensive set of functional-anatomic correlation studies in order to establish the degree of structural-functional correspondence. This system is expected to be applied in both cognitive and clinical neuroscience as an MRI-based topographic systematics of human forebrain anatomy with normative volumetric reference and also as a system of reference for the anatomic organization of specific neural systems as disrupted by focal lesions in lesion-deficit correlations.