Frontal Granular Cortex Research Articles

Brenda Milner: Pioneer of the Study of the Human Frontal Lobes

Although the behavioral effects of damage to the frontal lobes date back to at least the late 19th century even midway through the 20th century very little was known about human frontal lobe function and there was a general consensus that the frontal lobe did not play a key role in cognition. This all changed when Brenda Milner published a chapter in a 1964 volume entitled: The Frontal Granular Cortex and Behavior. Milner’s chapter, “Some effects of frontal lobectomy in man,” was the first systematic study of the effect of frontal lobe excisions on cognition in human patients. Milner had access to a unique population of frontal excision patients at the Montreal Neurological Institute that were being treated by Wilder Penfield and his associates for a wide range of neurological disorders, including intractable epilepsy. Milner and her colleagues engaged in a more than 50-year study that has had a formidable impact on our understanding of frontal lobe function. Paralleling studies of frontal lobe function in non-humans they influence on understanding the evolution and function of the prefrontal cortex of mammals. Thus, although Brenda Milner is best known for her studies of human memory, she has had an equally important contribution to our understanding of the frontal lobes.

Analysis Of The Cortical Hemodynamic Responses To Active-assistive Exercise In Individuals With Parkinson’S Disease.

Background: Gait and motor impairments are common symptoms in people with Parkinson’s disease (PD). Previous studies found active-assistive exercise to be effective in improving PD symptoms. The underlying neural mechanism contributing to these improvements is currently unknown. No previous studies have investigated how the brain responds to active-assistive exercise in people with PD. PURPOSE: To investigate the cortical hemodynamic responses to active-assistive exercise in individuals with PD. METHODS: A total of 7 individuals with PD (70.29 ± 5.44) and 10 controls (58.71 ± 9.30) participated in this cross-sectional study. All participants completed three modes of exercise including active exercise (AE), passive exercise (PE), and active-assistive exercise (AAE) using computerized cycling equipment (MOTOmed viva 2, RECK MOTOmed, Betzenweiler, Germany, 2017). Each mode of exercise was performed at a predetermined pace for 10 minutes on three separate days while a neuroimaging device, functional near-infrared spectroscopy (NIR Sport, NIRx Medical Technology, Berlin, Germany, 2017) captured oxy-hemoglobin (HbO) levels in the prefrontal lobe. RESULTS: Repeated measures ANOVA showed no significant difference in 𝚫;;;;HbO among exercise modes. A trend showed that the PD group displayed the greatest level of 𝚫;;;;HbO during PE and minimum with AE. A 2x3 mixed model ANOVA revealed no significant group x mode interaction. However, a trend showed that the PD group displayed greater levels of 𝚫;;;;HbO during PE and AAE whereas the control group revealed greater levels during AE and AAE. Four representative channels were selected for regional comparison of brain activation during AAE between groups. They demonstrated significant differences in the middle frontal cortex (p<.049), orbital cortex (p<.039), intermediate frontal cortex (p<.033), and granular frontal cortex (p<.022). CONCLUSION: Our findings suggest that people with PD showed higher levels of brain activity during passive and active-assistive modes of exercise as compared to active cycling. Brain activity levels during active-assistive exercise can be different when compared to those without PD. The results may help understand the underlying neural mechanism associated with positive outcomes following active-assistive exercise in PD.

Cognitive control of complex motor behavior in marmoset monkeys

Marmosets have attracted significant interest in the life sciences. Similarities with human brain anatomy and physiology, such as the granular frontal cortex, as well as the development of transgenic lines and potential for transferring rodent neuroscientific techniques to small primates make them a promising neurodegenerative and neuropsychiatric model system. However, whether marmosets can exhibit complex motor tasks in highly controlled experimental designs—one of the prerequisites for investigating higher-order control mechanisms underlying cognitive motor behavior—has not been demonstrated. We show that marmosets can be trained to perform vocal behavior in response to arbitrary visual cues in controlled operant conditioning tasks. Our results emphasize the marmoset as a suitable model to study complex motor behavior and the evolution of cognitive control underlying speech.

Intrinsic functional clustering of anterior cingulate cortex in the common marmoset

The common marmoset (Callithrix jacchus) has garnered recent attention as a potentially powerful preclinical model and complement to other canonical mammalian models of human brain diseases (e.g., rodents and Old World non-human primates). With a granular frontal cortex and the advent of transgenic modifications, marmosets are well positioned to serve as neuropsychiatric models of prefrontal cortex dysfunction. A critical step in the development of marmosets for such models is to characterize functional network topologies of frontal cortex in healthy, normally functioning marmosets. Here, we sought to characterize the intrinsic functional connectivity of anterior cingulate cortex (ACC) in marmosets using resting state functional magnetic resonance imaging (RS-fMRI). Seven lightly anesthetized marmosets were imaged at ultra-high field (9.4 T) and hierarchical clustering was employed to extract functional clusters of ACC from the RS-fMRI data. The data demonstrated three functionally discrete clusters within ACC. The functional connectivity between these clusters with the rest of the brain was also found to be distinct, supporting the hypothesis that ACC subregions serve different circuits and their concomitant functions. In a separate seed-based analysis, we also sought to delineate finer-grained patterns of ACC connectivity between marmoset primary motor area 4ab and putative eye movement areas (8aD and 8aV). This analysis demonstrated distinct patterns of ACC functional connectivity between motor and eye movement regions that overlapped well with what has been shown in humans and macaques. Overall, these results demonstrate that marmosets have a network topology of ACC that resembles that of Old World primates, giving further credence to the use of marmosets for preclinical studies of intractable human brain diseases.

Spatio-temporal extension in site of origin for cortical calretinin neurons in primates.

The vast majority of cortical GABAergic neurons can be defined by parvalbumin, somatostatin or calretinin expression. In most mammalians, parvalbumin and somatostatin interneurons have constant proportions, each representing 5–7% of the total neuron number. In contrast, there is a threefold increase in the proportion of calretinin interneurons, which do not exceed 4% in rodents and reach 12% in higher order areas of primate cerebral cortex. In rodents, almost all parvalbumin and somatostatin interneurons originate from the medial part of the subpallial proliferative structure, the ganglionic eminence (GE), while almost all calretinin interneurons originate from its caudal part. The spatial pattern of cortical GABAergic neurons origin from the GE is preserved in the monkey and human brain. However, it could be expected that the evolution is changing developmental rules to enable considerable expansion of calretinin interneuron population. During the early fetal period in primates, cortical GABAergic neurons are almost entirely generated in the subpallium, as in rodents. Already at that time, the primate caudal ganglionic eminence (CGE) shows a relative increase in size and production of calretinin interneurons. During the second trimester of gestation, that is the main neurogenetic stage in primates without clear correlates found in rodents, the pallial production of cortical GABAergic neurons together with the extended persistence of the GE is observed. We propose that the CGE could be the main source of calretinin interneurons for the posterior and lateral cortical regions, but not for the frontal cortex. The associative granular frontal cortex represents around one third of the cortical surface and contains almost half of cortical calretinin interneurons. The majority of calretinin interneurons destined for the frontal cortex could be generated in the pallium, especially in the newly evolved outer subventricular zone that becomes the main pool of cortical progenitors.

Functional localization within the prefrontal cortex: missing the forest for the trees?

Anatomical and functional studies of the prefrontal cortex (PFC) have identified multiple PFC subregions. We argue that the PFC is involved in cognitive functions exceeding the sum of specific functions attributed to its subregions. These can be revealed either by lesions of the whole PFC, or more specifically by selective disconnection of the PFC from certain types of information (for example, visual) allowing the investigation of PFC function in toto. Recent studies in macaque monkeys using the latter approach lead to a second conclusion: that the PFC, as a whole, could be fundamentally specialized for representing events that are extended in time. The representation of temporally complex events might underlie PFC involvement in general intelligence, decision-making, and executive function.

Postnatal development of layer IV in fronto-opercular region (Broca’s area)

Abstract In the adult human fronto-opercular cortex, the grade of granularity of cortical layer IV represents a major architectonic feature for distinguishing the opercular area BA44 (which is typically described as being magnopyramidal and intermedio-granular) from the triangular area BA45 (which is typically described as being magnopyramidal and granular). We analyzed postnatal cytoarchitectonic development of internal granular layer (layer IV) of the fronto-opercular region in 23 brains of newborns, infants and children (age range: 15 days to 15 years) and in one adult brain. We found that: (1) the grade of granularity of layer IV in the fronto-opercular cortex displays a great interindividual variability throughout development as well as in the adult brain; (2) this variability is much more pronounced in the opercular area BA44 than in the triangular area BA45. Our findings support the classical interpretation provided by Constantin von Economo (von Economo &amp; Koskinas, 1925) according to which BA44/FCBm represents a specialized variant of the wide premotor cortical zone, while BA45/FDG represents a specialized variant of the typical (associative) frontal granular cortex.

Increased d-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study

An important risk gene in schizophrenia is d-amino acid oxidase (DAAO). To establish if expression of DAAO is altered in cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of DAAO in a post-mortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral post-mortem samples (granular frontal cortex BA9, middle frontal cortex BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1–3, hippocampus (CA4), mediodorsal nucleus of the thalamus) from 10 schizophrenia patients to 13 normal subjects investigating gene expression of DAAO in the gray and white matter of both hemispheres of the above-mentioned brain regions by in situ-hybridization. We found increased expression of DAAO-mRNA in the hippocampal CA4 of schizophrenic patients. Compared to the control group, both hemispheres of the hippocampus of schizophrenic patients showed an increased expression of 46% (right, P = 0.013) and 54% (left, P = 0.019), respectively. None of the other regions examined showed statistically significant differences in DAAO expression. This post-mortem study demonstrated increased gene expression of DAAO in the left and right hippocampus of schizophrenia patients. This increased expression could be responsible for a decrease in local d-serine levels leading to a NMDA-receptor hypofunction that is hypothesized to play a major role in the pathophysiology of schizophrenia. However, our study group was small and results should be verified using larger samples.

Hans-Lukas Teuber and ‘The Riddle of Frontal Lobe Function in Man’ as Published in The Frontal Granular Cortex and Behavior (1964)

The edited text titled, “The Frontal Granular Cortex and Behavior” by Warren and Akert (1964) is based on an historic symposium held two years earlier at The Pennsylvania State University. Approximately half of the participants were to play major roles in the early development of neuropsychology and cognitive neuroscience and several of the topical presentations in this text are landmark articles for neuropsychology, but in this special issue of Neuropsychological Review (NPR) the work of Hans-Lukas Teuber and his legacy will be reviewed. Teuber’s (1964) article was titled “The riddle of frontal lobe function in man” and is reproduced in its entirety in this issue of NPR. While this review is written 44 years after Teuber’s seminal contribution, many riddles of frontal lobe function remain, but had neuropsychology adhered to some of the creative experimental designs that were the signature of Teuber’s research, we may have been much further along in solving the riddle. Teuber’s 1964 article provides a comprehensive review of known neuropsychological conundrums of frontal lobe function at that time, but more importantly, it framed the direction of future research and how neuropsychologists should conduct research. Now with contemporary neuroimaging methods many of the hypotheses that Teuber postulated more than four decades earlier can actually be tested. Teuber’s contributions to neuropsychology are considerable but this 1964 chapter, his careful research designs, cogent neuropsychological thinking and clear writing style, exemplified by this chapter, set the stage for numerous hypotheses that guided research that not only attempted to solve the “riddle” of frontal function but also that of higher cortical function. To best understand the importance of Teuber’s work, an historical perspective on the beginnings of neuropsychology is needed. While the term ‘neuropsychology’ is in common use today, it was not when Teuber began his academic and research career in the late 1940s, early 1950s. Indeed, a search of the National Library of Medicine shows that the first reference to the term ‘neuropsychology’ does not occur until 1950 and when most of those early references are reviewed, the term neuropsychology was being used synonymously with physiological psychology, where most of the work was animal based. This was recognized in the preface by Warren and Akert (1964) where the traditional domain of physiological psychology and animal based research was beginning to influence theories of human function and brain-behavior relationships. Warren and Akert state that “a genuine comparative methodology also implies the development of clear communication between those who work with patients in the clinic and those who work with experimental animals in the laboratory. This volume testifies at many points to the continuing and effective interchange of concepts and techniques among the researchers dealing with people and with animals” (p. v). Teuber’s work exemplified the cross over of animal-based physiological psychology to human-based neuropsychology, but Teuber’s first published use of the term ‘neuropsychology’ in the title of one of his articles does not occur until 1969 (see Teuber 1969). This makes it all the more remarkable that this 1964 publication anticipates and outlines the types of research paradigms that became the genesis for Neuropsychol Rev (2009) 19:9–24 DOI 10.1007/s11065-009-9086-1

The thalamic connections of motor, premotor, and prefrontal areas of cortex in a prosimian primate ( Otolemur garnetti)

Connections of motor areas in the frontal cortex of prosimian galagos ( Otolemur garnetti) were determined by injecting tracers into sites identified by microstimulation in the primary motor area (M1), dorsal premotor area (PMD), ventral premotor area (PMV), supplementary motor area (SMA), frontal eye field (FEF), and granular frontal cortex. Retrogradely labeled neurons for each injection were related to architectonically defined thalamic nuclei. Nissl, acetylcholinesterase, cytochrome oxidase, myelin, parvalbumin, calbindin, and Cat 301 preparations allowed the ventral anterior and ventral lateral thalamic regions, parvocellular and magnocellular subdivisions of ventral anterior nucleus, and anterior and posterior subdivisions of ventral lateral nucleus of monkeys to be identified. The results indicate that each cortical area receives inputs from several thalamic nuclei, but the proportions differ. M1 receives major inputs from the posterior subdivision of ventral lateral nucleus while premotor areas receive major inputs from anterior parts of ventral lateral nucleus (the anterior subdivision of ventral lateral nucleus and the anterior portion of posterior subdivision of ventral lateral nucleus). PMD and SMA have connections with more dorsal parts of the ventral lateral nucleus than PMV. The results suggest that galagos share many subdivisions of the motor thalamus and thalamocortical connection patterns with simian primates, while having less clearly differentiated subdivisions of the motor thalamus.

Do Rats Have Prefrontal Cortex? The Rose-Woolsey-Akert Program Reconsidered

Abstract Primates are unique among mammals in possessing a region of dorsolateral prefrontal cortex with a well-developed internal granular layer. This region is commonly implicated in higher cognitive functions. Despite the histological distinctiveness of primate dorsolateral prefrontal cortex, the work of Rose, Woolsey, and Akert produced a broad consensus among neuroscientists that homologues of primate granular frontal cortex exist in nonprimates and can be recognized by their dense innervation from the mediodorsal thalamic nucleus (MD). Additional characteristics have come to be identified with dorsolateral prefrontal cortex, including rich dopaminergic innervation and involvement in spatial delayed-reaction tasks. However, recent studies reveal that these characteristics are not distinctive of the dorsolateral prefrontal region in primates: MD and dopaminergic projections are widespread in the frontal lobe, and medial and orbital frontal areas may play a role in delay tasks. A reevaluation of rat frontal cortex suggests that the medial frontal cortex, usually considered to be homologous to the dorsolateral prefrontal cortex of primates, actually consists of cortex homologous to primate premotor and anterior cin-date cortex. The lateral MD-projection cortex of rats resembles portions of primate orbital cortex. If prefrontal cortex is construed broadly enough to include orbital and cingulate cortex, rats can be said to have prefrontal cortex. However, they evidently lack homologues of the dorsolateral prefrontal areas of primates. This assessment suggests that rats probably do not provide useful models of human dorsolateral frontal lobe function and dysfunction, although they might prove valuable for understanding other regions of frontal cortex.

Frontal granular cortex input to the cingulate (M3), supplementary (M2) and primary (M1) motor cortices in the rhesus monkey.

Although frontal lobe interconnections of the primary (area 4 or M1) and supplementary (area 6m or M2) motor cortices are well understood, how frontal granular (or prefrontal) cortex influences these and other motor cortices is not. Using fluorescent dyes in rhesus monkeys, we investigated the distribution of frontal lobe inputs to M1, M2, and the cingulate motor cortex (area 24c or M3, and area 23c). M1 received input from M2, lateral area 6, areas 4C and PrCO, and granular area 12. M2 received input from these same areas as well as M1; granular areas 45, 8, 9, and 46; and the lateral part of the orbitofrontal cortex. Input from the ventral part of lateral area 6, area PrCO, and frontal granular cortex targeted only the ventral portion of M1, and primarily the rostral portion of M2. In contrast, M3 and area 23c received input from M1, M2; lateral area 6 and area 4C; granular areas 8, 12, 9, 46, 10, and 32; as well as orbitofrontal cortex. Only M3 received input from the ventral part of lateral area 6 and areas PrCO, 45, 12vl, and the posterior part of the orbitofrontal cortex. This diversity of frontal lobe inputs, and the heavy component of prefrontal input to the cingulate motor cortex, suggests a hierarchy among the motor cortices studied. M1 receives the least diverse frontal lobe input, and its origin is largely from other agranular motor areas. M2 receives more diverse input, arising primarily from agranular motor and prefrontal association cortices. M3 and area 23c receive both diverse and widespread frontal lobe input, which includes agranular motor, prefrontal association, and frontal limbic cortices. These connectivity patterns suggest that frontal association and frontal limbic areas have direct and preferential access to that part of the corticospinal projection which arises from the cingulate motor cortex.

Cortical modulation of thalamo-cortical neurons relaying exteroceptive information: a microstimulation study in the guinea pig.

The nature and organization of cortical influences on somatosensory thalamic neurons were investigated in the guinea pig in order to ascertain if mechanisms subserving sensory-motor integration in the thalamus are as precise as has previously been demonstrated in the agranular frontal cortex (AGr) and granular parietal cortex (Gr). The study was carried out on 14 chronically-implanted awake animals. In each experiment one or two motor foci within AGr and Gr were identified according to the region of the movement evoked by intracortical microstimulation at the lowest threshold stimulation (usually 5-15 microA). Spontaneous activity of 182 thalamo-cortical single neurons was recorded in the nucleus ventralis thalami (VT). The neurons were also identified by their response to activation of cutaneous receptive fields (RFs) located in regions of vibrissae or limbs, and then tested for cortical stimulation with a pulse intensity equal to the threshold for evoking motor effects. During the cortico-thalamic tests, the duration of stimulating trains was reduced in order to avoid the appearance of limb or vibrissa movements which could activate somatosensory ascending pathways forwarding peripheral messages to VT. The cortical control on VT neurons appears to be organized in a very precise manner. It was seen that: 1) The influences on these neurons relaying exteroceptive signals specifically emanated from AGr and Gr areas which in turn received exteroceptive input. 2) The vibrissa units responded to stimulation of foci in either AGr or Gr but the reactivity was greater upon stimulation of Gr than AGr. The incidence of responses was very high when the vibrissa RF was overlapping or adjacent to the region of the cortically-evoked vibrissa movement. The response pattern was mostly excitatory. Responses were rarely observed when vibrissa RF lay distant from the vibrissa moved by cortical stimulation. 3) Neurons with limb RFs responded constantly to stimulation of Gr foci only when the RF was overlapping or adjacent to the region of the cortical motor target; in these two conditions the response pattern was excitatory and inhibitory, respectively. Inhibitions only concerned neurons with forelimb RFs. Responses to stimulation of AGr were rarely obtained. From a functional point of view, the excitatory nature of the cortical control on thalamo-cortical VT neurons suggests that a cortical signal inducing movement of a given body part is able to enhance the afferent transmission of somatosensory messages arising in the same body part.(ABSTRACT TRUNCATED AT 400 WORDS)

Ipsilateral cortical connections of granular frontal cortex in the strepsirhine primate Galago, with comparative comments on anthropoid primates

Modern studies of granular frontal cortex (GFC) in large-brained, anthropoid primates, such as Macaca, indicate that this region is comprised of many areal subdivisions. These areas vary in their architectonic appearance and each has a distinctive, diverse set of corticocortical connections. The great extent of the GFC region in anthropoids, and its high degree of areal parcellation, suggest that some GFC areas may be specializations of anthropoids, not found in other mammals. To investigate this possibility, we studied the corticocortical connections of GFC in the relatively small-brained, strepsirhine primate Galago, with a series of eight tracer injections in the frontal cortex, and an additional eight injections of parietal and temporal cortex. Tracers used were wheat-germ agglutinin conjugated to horseradish peroxidase and tritiated amino acids. Our results indicate that Galago GFC has strong, reciprocal connections with the parietal area-7 complex and with higher-order temporal areas; there are additional connections with extrastriate visual cortex, parahippocampal, and cingulate areas, and frontal cortex. Thus GFC has an extremely diverse array of cortical connections in Galago, as in Macaca. However, we also found that the pattern of parietofrontal connections is simpler in Galago than in Macaca. Specifically, parietal areas project to fewer discrete zones within the GFC of Galago, consistent with the view that these animals have fewer GFC areas than Macaca. In addition, Galago GFC possesses connections that specifically resemble those of Macaca arcuate cortex, but lacks connectional patterns that are characteristic of principalis cortex. These results are in accord with our previous architectonic studies, which indicated that Galago does not possess homologues of principalis areas. We conclude that the arcuate areas are common elements of primate GFC organization, while the areas located within and adjacent to the principal sulcus are anthropoid specializations.

Myelo‐ and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca

As the first part of a comparative investigation of primate frontal cortex, we compared the frontal architectonic organization of Galago, a small-brained, strepsirhine (or "prosimian") primate, to that of an anthropoid primate, Macaca, by using myelin- and Nissl-stained material. We were able to distinguish many more areas in both taxa than have been recognized in most previous studies of the primate frontal lobe. In particular, we were able to subdivide many of the areas shown in the commonly cited architectonic map of Walker (J. Comp. Neurol. 73:59-86, 1940). Delineation of areas was greatly facilitated by the use of the Gallyas technique for staining myelin. The areal organization of much of frontal cortex (specifically, the premotor, orbital, and medial regions) appears to be very similar in Galago and Macaca. In these regions, we were able to recognize the same complement of areas in both taxa, with few exceptions. In the granular frontal cortex (GFC), by contrast, we were able to distinguish about twice as many areas in Macaca as in Galago. For most of the GFC areas of Galago, there are architectonically similar areas in Macaca; the areas shared by both taxa correspond mainly to the arcuate and superior areas of Macaca (i.e., the region encompassed by Walker's areas 45, 8A, and 8B). However, there are many additional, more rostral, areas in Macaca for which there are no obvious homologues in Galago. In particular, Galago lacks cortex resembling the distinctive, lightly myelinated cortex of the Macaca principal sulcus (Walker's area 46 and its subdivisions). Our results are difficult to reconcile with the view that frontal lobe organization varies little across taxa. Rather, they suggest that granular frontal cortex underwent considerable change during primate evolution, including the addition of new areas in anthropoids.

Multiple Representations of the Body and Input-Output Relationships in the Agranular and Granular Cortex of the Chronic Awake Guinea Pig

The organization of somatosensory input and the input-output relationships in regions of the agranular frontal cortex (AGr) and granular parietal cortex (Gr) were examined in the chronic awake guinea pig, using the combined technique of single-unit recording and intracortical microstimulation (ICMS). AGr, which was cytoarchitectonically subdivided into medial (AGrm) and lateral (AGrl) parts, also can be characterized on a functional basis. AGrl contains the head, forelimb, and most hindlimb representations; only a small number of hindlimb neurons are confined in AGrm. Different distributions of submodalities exist in AGr and Gr: AGr receives predominantly deep input (with the exception of the vibrissa region, which receives cutaneous input), whereas neurons of Gr respond almost exclusively to cutaneous input. The cutaneous or deep receptive field (RF) of each neuron was determined by natural peripheral stimulation. All studied neurons were activated by small RFs, with the exception of lip, nose, pinna, and limb units of lateral Gr (Grl), for which the RFs were larger. Microelectrode mapping experiments revealed the existence of three spatially separate, incomplete body maps in which somatosensory and motor representations overlap. One body map, with limbs medially and head rostrolaterally, is contained in AGr. A second map, comparable to the first somatosensory cortex (SI) of other mammals, is found in Gr, with hindlimb, trunk, forelimb, and head representations in an orderly mediolateral sequence. An unresponsive zone separates the head area from the forelimb region. A third map, with the forelimb rostrally and the hindlimb caudally, lies adjacent and lateral to the SI head area. This limb representation, which is characterized by an upright and small size compared to that found in SI, can be considered to be part of the second somatosensory cortex (SII). A distinct head representation was not recognized as properly belonging to SII, but the evidence that neurons of the SI head region respond to stimulation of large RFs located in lips, nose, and pinna leads us to hypothesize that the SII face area overlaps that of SI to some extent, or, alternatively, that the two areas strictly contiguous and the limits are ambiguous, making them difficult to distinguish. The input-output relationships were based on the results of RF mapping and ICMS in the same electrode penetration. The intrinsic specific interconnections of cortical neurons whose afferent input and motor output is related to identical body regions show a considerable degree of refinement.(ABSTRACT TRUNCATED AT 400 WORDS)

Connections of the ventral granular frontal cortex of macaques with perisylvian premotor and somatosensory areas: anatomical evidence for somatic representation in primate frontal association cortex.

In macaque monkeys with injections of tritiated amino acids or horseradish peroxidase in the ventrolateral granular frontal cortex, we observed extensive anterograde and retrograde labeling of the premotor and somatosensory cortex in and around the lateral sulcus. Comparable labeling was not present with large and small control injections of the dorsal granular cortex. Cytoarchitectonic evaluation of the perisylvian cortex in the three cases examined in detail indicated that labeled areas included the ventral premotor cortex (area 6V); the precentral opercular and orbitofrontal opercular areas (PrCO and OFO); the second somatosensory area (S-II); the opercular cortex immediately anterior to S-II, possibly corresponding to area 2 of the S-I complex; and the central part of the insular cortex, including portions of the granular and dysgranular insular fields (Ig, Idg). Labeling was particularly dense and extensive in areas 6V, S-II, and OFO. Lighter labeling was also present in the rostral inferior parietal lobule (areas 7b and POa). The distribution of label within perisylvian areas was not uniform: certain parts were heavily labeled, while other parts were lightly labeled or unlabeled. Comparison of label distribution with published accounts of the somatotopy of these areas indicates that forelimb and orofacial representations were selectively labeled. Further, our results, taken together with other recent anatomical findings (e.g., Matelli et al.: Journal of Comparative Neurology 251:281-298, 1987; Barbas and Pandya: Journal of Comparative Neurology 256:211-228, 1987) suggest strongly that there is a network of interconnected forelimb and orofacial representations in macaque cortex, involving the ventral granular frontal cortex, area 6V, OFO, opercular area 2, S-II, the central insula, and area 7b. Each injection of frontal cortex which labeled the perisylvian somatic cortex involved the cortex of the ventral rim of the principal sulcus (PSvr). The cortex surrounding the PSvr does not stand out as a distinct area in Nissl-stained material. However, examination of myelin-stained sections prepared from uninjected hemispheres with the Gallyas technique revealed the existence of a distinct zone centered on the PSvr. This myeloarchitectonic area, which we term area 46vr, is more heavily myelinated than the ventral bank and fundus of the principal sulcus (area 46v) but is less heavily myelinated than the ventral (inferior) convexity (area 12). Involvement of area 46vr in our injections was probably responsible for the strong labeling observed in perisylvian somatic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

The prefrontal corticotectal projection in the monkey; An anterograde and retrograde horseradish peroxidase study

The prefrontal corticotectal projection was studied in macaque and cebus monkeys using the horseradish peroxidase technique. Following stereotaxic horseradish peroxidase injections into the superior colliculus, large numbers of retrogradely-labelled corticotectal neurons were observed in the prearcuate frontal eye field cortex, dorsal and ventral convexity and sulcus principalis cortex, as well as on the medial aspect of the prefrontal cortex. These experiments, taken together with anterograde data derived from other cases in which horseradish peroxidase gel implants were made in various subregions of the granular prefrontal cortex, suggested a topographic organization of prefrontal projections to the tectum. Area 8 (frontal eye field) primarily projected to the stratum intermedium. The dorsal sulcus principalis cortex projected most heavily to the deeper stratum intermedium, stratum profundum and central gray matter, and gave rise to a characteristic line of puffs in the dorsal stratum intermedium. The rostral dorsal convexity and medial prefrontal cortex projected primarily to the stratum profundum and central gray matter. The orbitofrontal cortex lacked projections to the superior colliculus and only contained retrogradely-labelled neurons when the injection spread into the central gray matter. It was also observed that prefrontal corticotectal fibers followed 2 divergent routes to the superior colliculus: the classically-described ‘pedunculo-tegmental’ route, and a ‘transthalamic’ pathway. This more detailed description of a major cortical input to the tectum not only contributes to our understanding of the functional organization of both the granular frontal cortex and the colliculus, but suggests anatomical connectivity which may underlie their roles in oculomotor mechanisms.

Projection of precentral motor cortex upon nucleus medialis dorsalis thalami in the monkey

The efferent connections of the lateral aspects of the precentral, premotor and granular frontal cortex were reexamined in 12 monkeys ( Macaca fascicularis) by means of anterograde labelling techniques using radioactive proline and leucine. A distinct projection of the precentral gyrus upon the paralamellar portion of the nucleus medialis dorsalis (MD) was observed. The somatotopic arrangement within this projection is less well defined than within the ventrolateral thalamic complex. The facial division of area 4 has not only a marked ipsilateral but in contrast to the body representation also a distinct if much weaker contralateral projection. No label was found in MD after injections in the postcentral gyrus. Thus, MD represents a thalamic link between agranular (motor) and granular (association) cortex of the frontal lobe.

The efferent projections of the medial prefrontal cortex in the squirrel monkey ( Saimiri sciureus)

Unilateral partial ablations were made in the medial granular frontal cortex of 6 adult squirrel monkeys. Fiber degeneration was traced using the Nauta-Gygax and Fink-Heimer selective silver impregnation techniques into the cingulum, uncinate fascicle, corpus callosum, internal capsule and sublenticular (ventral extracapsular) bundle. Corticocortical projections were observed to the lateral orbital, parietal, rostral inferior temporal, and entorhinal cortices, as well as to the hippocampus proper. Subcortical projections were observed to the basal amygdaloid nucleus, lateral hypothalamus, lateral dorsal, anterior ventral, mediodorsal, pulvinar, and intralaminar nuclei of the thalamus. Preterminal and terminal fiber degeneration were notably sparse in most of the neostriatum, except the dorsolateral region of the caudate nucleus. Fiber degeneration traversed the medial crus cerebri of the midbrain, where fibers of passage ascended into the tegmentum through the medial substantia nigra. Preterminal and terminal degeneration were present in the mesencephalic reticular formation lateral and dorsal to the red nucleus and a few degenerating fibers were followed into the dorsolateral periaqueductal gray. Degeneration was observed as far caudal as the reticulotegmental nucleus of the rostral pons. On the basis of its connections, the medial prefrontal cortex resembles the remainder of the prefrontal lobe and probably also has an important role in cortical and subcortical limbic mechanisms.