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. © 1993 Wiley-Liss,Inc.     

精神分裂症首次发病未治疗患者静息态下局部脑区自发活动的研究

目的探讨精神分裂症首次发病未治疗患者静息态下局部脑区自发活动的情况:方法:利用低频振幅(ALFF)方法,对27例首次发病未治疗的精神分裂症患者(患者组)进行静息状态下功能磁共振(fMRI)扫描,对影像学数据进行ALFF方法处理,结果与22名年龄、性别及受教育程度相匹配的健康对照者(正常对照组)比较。结果:与正常对照组相比,患者组ALFF显著增高的脑区是运动前区、辅助运动区和眶额回;ALFF显著降低的脑区是楔前叶、后扣带回、内侧前额叶和角回(P0.05,Alphaism矫正)。结论:精神分裂症首次发病未治疗患者在静息态下运动前区、辅助运动区、眶额回、楔前叶、后扣带回、内侧前额叶和角回的局部脑区自发活动异常,这些异常脑区可能有助于解释精神分裂症的病理机制。     

Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey.

The orbitofrontal cortex of the monkey can be subdivided into a caudal agranular sector, a transitional dysgranular sector, and an anterior granular sector. The neural input into these sectors was investigated with the help of large horseradish peroxidase injections that covered the different sectors of orbitofrontal cortex. The distribution of retrograde labeling showed that the majority of the cortical projections to orbitofrontal cortex arises from a restricted set of telencephalic sources, which include prefrontal cortex, lateral, and inferomedial temporal cortex, the temporal pole, cingulate gyrus, insula, entorhinal cortex, hippocampus, amygdala, and claustrum. The posterior portion of the orbitofrontal cortex receives additional input from the piriform cortex and the anterolateral portion from gustatory, somatosensory, and premotor areas. Thalamic projections to the orbitofrontal cortex arise from midline and intralaminar nuclei, from the anteromedial nucleus, the medial dorsal nucleus, and the pulvinar nucleus. Orbitofrontal cortex also receives projections from the hypothalamus, nucleus basalis, ventral tegmental area, the raphe nuclei, the nucleus locus coeruleus, and scattered neurons of the pontomesencephalic tegmentum. The non-isocortical (agranular-dysgranular) sectors of orbitofrontal cortex receive more intense projections from the non-isocortical sectors of paralimbic areas, the hippocampus, amygdala, and midline thalamic nuclei, whereas the isocortical (granular) sector receives more intense projections from the dorsolateral prefrontal area, the granular insula, granular temporopolar cortex, posterolateral temporal cortex, and from the medial dorsal and pulvinar thalamic nuclei. Retrograde labeling within cingulate, entorhinal, and hippocampal cortices was most pronounced when the injection site extended medially into the dysgranular paraolfactory cortex of the gyrus rectus, an area that can be conceptualized as an orbitofrontal extension of the cingulate complex. These observations demonstrate that the orbitofrontal cortex has cytoarchitectonically organized projections and that it provides a convergence zone for afferents from heteromodal association and limbic areas. The diverse connections of orbitofrontal cortex are in keeping with the participation of this region in visceral, gustatory, and olfactory functions and with its importance in memory, motivation, and epileptogenesis.     

Reduced volume of orbitofrontal cortex in major depression.

BACKGROUND: Functional neuroimaging studies have implicated dysfunction of orbitofrontal cortex in the symptoms of depression, and a recent postmortem study of depressed patients found reduced density of neurons and glia in this area. The purpose of this study was to measure volume of orbitofrontal cortex and other frontal cortical subregions in patients with major depression. METHODS: Magnetic resonance imaging was used to measure volume of the orbitofrontal cortex and other frontal cortical regions in patients with major depression in remission (n = 15) and comparison subjects (n = 20). RESULTS: Patients with depression had a statistically significant 32% smaller medial orbitofrontal (gyrus rectus) cortical volume, without smaller volumes of other frontal regions including anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain volume. The findings were significant after statistically controlling for brain size. CONCLUSIONS: These findings are consistent with smaller orbitofrontal cortical volume in depression.     

The duality of the cingulate gyrus in monkey. Neuroanatomical study and functional hypothesis

According to most behavioural, electrophysiological, and clinical studies, the cingulate gyrus is widely thought to be involved in regulation of emotional life, reactivity to painful stimuli, memory processing, and attention to sensory stimuli. Anatomically the cingulate cortex is composed of two distinct areas numbered 24 and 23 in Brodmann's classification. We have investigated the connections of the cingulate gyrus in monkeys, using horseradish peroxydase and radioautographic techniques, in order to verify the hypothesis of an anatomical complementarity of these cytoarchitectonic subdivisions. The posterior cingulate gyrus (area 23) is specifically connected with the associative temporal cortex, the medial temporal and orbitofrontal cortices, and with the medial pulvinar. The anterior cingulate gyrus (area 24) is related to the intralaminar, mediodorsal, and ventral anterior thalamic nuclei, the amygdala, and the nucleus accumbens septi. The two cingulate areas were found to be interconnected and to have, in common, connections with the 'limbic' thalamic nuclei (AM, AV, LD), the caudate nucleus, the claustrum, the lateral frontal and the posterior parietal (area 7) cortices.     

Brain areas activated by uncertain reward-based decision-making in healthy volunteers

Reward-based decision-making has been found to activate several brain areas, including the ven- trolateral prefronta~ lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three de- grees of uncertainty in a reward-based decision-making task （certain, risky, and ambiguous）. The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to ana- lyze the location and intensity of activation during the reward-based decision-making task, with re- spect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the ＇risk＇ condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during am- biguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbi- tofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, infe- rior parietal Iobule, and cerebellar posterior lobe exhibited greater activation in the ＇risk＇ than in the ＇certain＇ condition （P 〈 0.05）. The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the ＇ambiguous＇ condition compared to the ＇risk＇ condition （P 〈 0.05）. The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during deci- sion-making about uncertain rewards. Thus, we observed different levels and regions of activation for different types of reward processing during decision-making. Specifically, when the degree of reward uncertainty increased, the number of activated brain areas increased, including greater ac- tivation of brain areas associated with loss.     

Cortical and subcortical distribution of middle and long latency auditory and visual evoked potentials in a cognitive (CNV) paradigm

OBJECTIVE: This study concerned sensory processing (post-stimulus late evoked potential components) in different parts of the human brain as related to a motor task (hand movement) in a cognitive paradigm (Contingent Negative Variation). The focus of the study was on the time and space distribution of middle and late post-stimulus evoked potential (EP) components, and on the processing of sensory information in the subcortical-cortical networks. METHODS: Stereoelectroencephalography (SEEG) recordings of the contingent negative variation (CNV) in an audio-visual paradigm with a motor task were taken from 30 patients (27 patients with drug-resistant epilepsy; 3 patients with chronic thalamic pain). The intracerebral recordings were taken from 337 cortical sites (primary sensorimotor area (SM1); supplementary motor area (SMA); the cingulate gyrus; the orbitofrontal, premotor and dorsolateral prefrontal cortices; the temporal cortex, including the amygdalohippocampal complex; the parietooccipital lobes; and the insula) and from subcortical structures (the basal ganglia and the posterior thalamus). The concurrent scalp recordings were obtained from 3 patients in the thalamic group. In 4 patients in the epilepsy group, scalp recordings were taken separately from the SEEG procedure. The middle and long latency evoked potentials following an auditory warning (S1) and a visual imperative (S2) stimuli were analyzed. The occurrences of EPs were studied in two time windows (200-300 ms; and over 300 ms) following S1 and S2. RESULTS: Following S1, a high frequency of EP with latencies over 200 ms was observed in the primary sensorimotor area, the supplementary motor area, the premotor cortex, the orbitofrontal cortex, the cingulate gyrus, some parts of the temporal lobe, the basal ganglia, the insula, and the posterior thalamus. Following S2, a high frequency of EP in both of the time windows over 200 ms was observed in the SM1, the SMA, the premotor and dorsolateral prefrontal cortex, the orbitofrontal cortex, the cingulate gyrus, the basal ganglia, the posterior thalamus, and in some parts of the temporal cortex. The concurrent scalp recordings in the thalamic group of patients twice revealed potentials peaking approximately at 215 ms following S1. Following S2, EP occurred with latencies of 215 and 310 ms, respectively. Following S1, separate scalp recordings in 4 patients in the epilepsy group displayed EP 3 times in the 'over 300 ms' time window. Following S2, EP were presented once in the '200-300 ms' time window and 3 times in the 'over 300 ms' time window. CONCLUSIONS: The SM1, the SMA, multiple sites of the frontal lobe, some parts of the temporal lobe, the cingulate gyrus, the basal ganglia, the insula, and the posterior thalamus all participate in a cortico-subcortical network that is important for the parallel cognitive processing of sensory information in a movement related task.     

Cortical and subcortical afferent connections of a posterior division of feline area 7 (area 7p)

Area 7 of the cat, as identified cytoarchitecturally, includes cortex both on the middle suprasylvian gyrus and on the anterior lateral gyrus. The aim of the experiments reported here was to determine whether within this zone there are subdivisions with qualitatively different patterns of afferent connectivity. Deposits of distinguishable retrograde tracers were placed at 29 sites in and around area 7 of 15 cats; cortical and subcortical telencephalic structures were then scanned for retrograde labeling. Our results indicate that cortex on the anterior lateral gyrus, although often included in area 7, is indistinguishable on connectional grounds from adjacent somesthetic cortex (area 5b). Cortex with strong links to visual, oculomotor, and association areas is confined to the middle suprasylvian gyrus and the adjacent lateral bank of the lateral sulcus. We refer to this discrete, connectionally defined zone as posterior area 7 (area 7p). Area 7p receives input from visual areas 19, 20a, 20b, 21a, 21b, AMLS, ALLS, and PLLS; from frontal oculomotor cortex (areas 6m and 6l); and from cortical association areas (posterior cingulate cortex, the granular insula, the posterior ectosylvian gyrus, and posterior area 35). Thalamic projections to area 7p arise from three specific nuclei (pulvinar; nucleus lateralis intermedius, pars caudalis; nucleus ventralis anterior) and from the intralaminar complex (nuclei centralis lateralis, paracentralis and centralis medialis). Neurons in a division of the claustrum immediately beneath the somatosensory and visual zones project to area 7p. Within area 7p, anterior-posterior regional differentiation is present, as indicated by the spatial ordering of projections from cingulate and frontal cortex, the thalamus, and the claustrum. Area 7p, as delineated by connectional analysis in this study, resembles cortex of the primate inferior parietal lobule both in its location relative to other cortical districts and in its pattern of neural connectivity.     

Connections of the parahippocampal cortex. I. Cortical afferents

In the present study in the cat the parahippocampal cortex denotes the caudoventral part of the limbic lobe and is composed of the entorhinal and perirhinal cortices. The cytoarchitecture of these areas and their borders with adjacent cortical areas are briefly discussed. The organization of the cortical afferents of the parahippocampal cortex was studied with the aid of retrograde and anterograde tracing techniques. In order to identify the source of cortical afferents, injections of retrograde tracers such as wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP), or the fluorescent substances fast blue or nuclear yellow, were placed in different parts of the parahippocampal cortex. In an attempt to further disclose the topographical and laminar organization of the afferent pathways, injections of tritiated amino acids were placed in cortical areas that were found to project to the parahippocampal cortex. The results of these experiments indicate that fibers from olfactory-related areas, the hippocampus, and other parts of the limbic cortex project only to the entorhinal cortex. The afferents from olfactory structures terminate predominantly superficially, whereas hippocampal and limbic cortical afferents are directed mainly to layers deep to the lamina dissecans. Paralimbic areas, including the anterior cingulate and the prelimbic cortices on the medial aspect, and the orbitofrontal and granular and agranular insular cortices on the lateral aspect of the hemisphere, project to the entorhinal cortex and medial parts of area 35 of the perirhinal cortex. These mostly mesocortical afferents terminate in both the superficial and deep layers of the entorhinal and perirhinal cortices. Parasensory association areas, which form part of the neocortex, do not project farther medially in the parahippocampal cortex than the perirhinal areas 35 and 36. These afferents mainly stem from a rather wide rim of neocortex that lies directly adjacent to area 36 and extends from the posterior sylvian gyrus via the posterior ectosylvian gyrus into the posterior suprasylvian gyrus. There is a rostrocaudal topographical arrangement in these projections such that rostral cortical areas distribute more rostrally and caudal parts project to more caudal parts of the perirhinal cortex. The cortex of the posterior suprasylvian gyrus contains the paravisual areas 20 and 21. The posterior sylvian gyrus most probably represents a para-auditory association area, whereas the most ventral part of the posterior ectosylvian gyrus may constitute a convergence area for visual and auditory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Intracortical recordings of early pain-related CO2-laser evoked potentials in the human second somatosensory (SII) area.

We studied responses of the parieto-frontal opercular cortex to CO2-laser stimulation of A delta fiber endings, as recorded by intra-cortical electrodes during stereotactic-EEG (SEEG) presurgical assessment of patients with drug-resistant temporal lobe epilepsy. After CO2-laser stimulation of the skin at the dorsum of the hand, we consistently recorded in the upper bank of the sylvian fissure contralateral to stimulation, a negative response at a latency of 135 +/- 18 ms (N140), followed by a positivity peaking around 171 +/- 22 ms (P170). The stereotactic coordinates in the Talairach's atlas of the electrode contacts recording these early responses covered the pre- and post-rolandic part of the upper bank of the sylvian fissure (-27 < y < +12 mm; 31 < x < 57 mm; 4 < z < 23 mm), corresponding to the accepted localization of the SII area in man, possibly including the upper part of the insular cortex. The spatial distribution of these early contralateral responses in the SII-insular cortex fits wit that of the modeled sources of scalp CO2-laser evoked potentials (LEPs) and with PET data from pain activation studies. Moreover, this study showed the likely existence of dipolar sources radial to the scalp surface in SII, which are overlooked in magnetic recordings. Early responses also occurred in the SII area ipsilateral to stimulation peaking 15 ms later than in contralateral SII, suggesting a callosal transmission of nociceptive inputs between the two SII areas. Other pain responsive areas such as the anterior cingulate gyrus, the amygdala and the orbitofrontal cortex did not show early LEPs in the 200 ms post-stimulus. These findings suggest that activation of SII area contralateral to stimulation, possibly through direct thalamocortical projections, represents the first step in the cortical processing of peripheral A delta fiber pain inputs.     

Cortico-cortical connections of somatic sensory cortex (areas 3, 1 and 2) in the rhesus monkey.

The connections of areas 3, 1 and 2 in the postcentral gyrus of the rhesus monkey are investigated using ablation-degeneration techniques following both full depth lesions and lesions which involved fewer than six cortical layers. Analysis of the topographic and laminar organization of these connections reveal that each of these areas has a differential connection pattern both within the parietal lobe and with respect to motor cortex. Area 3 projects predominantly to area 1 via a horizontal, intracortical fiber system which courses through layers III and V without entering the white matter while other efferents of area 3 to areas 2, 3a and second somatosensory cortex (SII) are less dense and course through the white matter. There is no indication that area 3 efferents terminate in areas 4 or 5. In comparison to area 3, area 1 has a wider projection field. Its primary outflow reaches area 2 via a white matter course while moderately strong connections are directed to areas 3a, S II, 4 and supplementary motor cortex (M II) and a minor projection to area 5. Lesions involving the supragranular layers of area 1 demonstrate that efferents from these layers (II-III) travel directly through the cortex to terminate in layer I of area 3 as well as entering the white matter before terminating in area 2 ventral to the tip of the intraparietal sulcus. Finally, area 2 projects primarily to area 5 via both an intracortical fiber system in layers III-V as well as through the white matter. While area 2 also has connections with areas 1, 3a, S II, 6 and M II, it was not observed to project to area 3. In addition, layers I-IV of area 2 ventral to the intraparietal sulcus send a number of horizontally oriented fibers mainly through layer IIIb to terminate in rostral area 7 (area PF of Bonin and Bailey, '47). Thus, the projections of these three subdivisions of the postcentral gyrus indicate that there is a strong and sequential outflow of connections from area 3 to areas 1 and 2, then from area 1 to area 2 and finally from area 2 to area 5 and rostral area 7. Each of these connections originates to a large extent from the supragranular layers. In contrast, connections of these areas in the opposite direction toward the central sulcus are less pronounced.     

Direct and indirect pathways from the amygdala to the frontal lobe in rhesus monkeys

To elucidate the anatomical relationships between the frontal association cortex and the limbic system in primates, projections from the amygdala to frontal cortex were studied in the rhesus monkey using retrograde and anterograde tracing methods. Following injections of horseradish peroxidase (HRP) into the orbital prefrontal cortex, the gyrus rectus, the superior frontal gyrus, and the anterior cingulate gyrus of the frontal lobe, labeled neurons were found in the basolateral, basomedial, or basal accessory nuclei of the amygdala. None of these nuclei contained labeled neurons following HRP injections into the principal sulcus or the lateral inferior convexity of the frontal lobe. This selective distribution of amygdala connections was confirmed by injection tritiated amino acids into the amygdala. Silver grains were present only over the orbital cortex and gyrus rectus on the ventral surface of the frontal lobe and over the superior prefrontal gyrus and anterior cingulate gyrus on the medial wall of the hemisphere, while the dorsolateral prefrontal cortex was free of radioactivity. The isotope injection of the amygdala also revealed a projection to the magnocellular moiety of the mediodorsal nucleus (MDmc) which is known to innervate the same ventromedial regions of the frontal lobe that receive direct connections from the amygdala. Although MDmc and amygdala project to the same cortical regions, their terminal fields are different. The direct amygdala input terminates in layer 1 in orbital cortex and gyrus rectus and layer 2 in the dorsomedial cortex and cingulate gyrus, while the thalamic input is primarily to layer 3 and, in some areas, also the superficial half of layer 1. These findings indicate that the frontal lobe of rhesus monkeys can be subdivided into two separable cortical regions: 1) A ventromedial region including the anterior cingulate gyrus which receives both direct (amygdalo-cortical) and indirect (amygdalo-thalamo-cortical) input from the amygdala; and 2) a dorsolateral frontal region which is essentially devoid of either direct or indirect amygdalofugal axons. On the basis of its selective relationship with the amygdala, the ventromedial region may be considered the "limbic" portion of the frontal association cortex.     

Anatomical evidence for medial pulvinar connections with the posterior cingulate cortex, the retrosplenial area, and the posterior parahippocampal gyrus in monkeys

Reciprocal connections between the medial pulvinar and the limbic neocortex in monkeys were demonstrated by means of tritiated amino acid injections in the medial pulvinar and the cingulate cortex, and HRP injections in the medial pulvinar. It appears that the medial nucleus of the pulvinar sends projection fibres to the posterior cingulate gyrus (area 23), the retrosplenial area, and the posterior parahippocampal gyrus (areas TH and TF). The labeled terminals were concentrated in two bands, one in the deeper part of layer III and in layer IV, and the other in layer I. These projections were observed to be reciprocal, and the cortical afferent fibers to the medial pulvinar were found to originate from the deep layers of the cortex. The medial nucleus of the pulvinar was already known to be connected with the prefrontal cortex and with the inferior parietal lobule. Since this nucleus is now demonstrated to be connected with the posterior limbic neocortex, it is envisaged as being the thalamic counterpart of a cortical triad (prefrontal, parietal, and limbic) involved in modulating directed attention.     

Anatomical and experimental study of certain association fascicles in the cortex of the rabbit (Oryctalagus cuniculus).

1. All lesions resulted in degeneration of the short intracortical association fibers in cortical layer I and of the short subcortical fibers which extended to the corona radiata before ending in the deeper layers of the overlying neopallium. 2. From all the lesions fibers were traced through the corona radiata to the subcallosal or the so-called superior fronto-occipital association bundle. This bundle had projection fibers to the orbitofrontal cortex. 3. From the lesion in the orbitofrontal neopallium, the orbitofrontal-pyriform connections were established. Such fibers coursed on the dorsal edge of the lateral olfactory tract and distributed to the pyriform cortex and to the nucleus of the lateral olfactory tract. 4. The uncinate fasciculus of man derived its name from its arching course from the base of the frontal lobe to the temporal lobe. Because of the more caudal position of the amygdala in the rabbit, the comparable fasciculus passed directly caudally and exhibited only slight arching. This fasciculus in the rabbit had the typical dorsal and ventral parts. The dorsal part arose from the orbitofrontal cortex to distribute to the pyriform and the temporal lobe cortices. The ventral portion extended into the olfactory tuberculum and the anterior amygdaloid area. 5. The paraventricular component of the transverse frontal fasciculus interconnected the neopallium with the medial part of the olfactory tuberculum. It had origins in the frontal and possibly in other neocortical areas. 6. The cingulum interconnected the medial portion of the olfactory tubercle, the septum, the various cingulate areas and areas of the neopallium with each other. 7. Therefore, the New Zealand white rabbit had short association fibers which were mainly neopallial in origin and termination and long association fibers which had both a neopallial and a limbic component.     

Convergence of Limbic Input to the Cingulate Motor Cortex in the Rhesus Monkey

Limbic system influences on motor behavior seem widespread, and could range from the initiation of action to the motivational pace of motor output. Motor abnormalities are also a common feature of psychiatric illness. Several subcortical limbic-motor entry points have been defined in recent years, but cortical entry points are understood poorly, despite the fact that a part of the limbic lobe, the cingulate motor cortex (area 24c or M3, and area 23c or M4), contributes axons to the corticospinal pathway. Using retrograde and anterograde tracers in rhesus monkeys, we investigated the ipsilateral limbic input to area 24c and adjacent area 23c. Limbic cortical input to areas 24c and 23c arise from cingulate areas 24a, 24b, 23a, 23b, and 32, retrosplenial areas 30 and 29, and temporal areas 35, TF and TH. Areas 24c and 23c were also interconnected strongly. The dysgranular part of the orbitofrontal cortex and insula projects primarily to area 24c while the granular part of the orbitofrontal cortex and insula projects primarily to area 23c. Afferents from cingulate area 25, the retrocalcarine cortex, temporal pole, entorhinal cortex, parasubiculum, and the medial part of area TH target primarily or only area 24c. Our findings indicate that a variety of telencephalic limbic afferents converge on cortex lining the lower bank and fundus of the anterior part of the cingulate sulcus. Because it is known that this cortex gives rise to axons ending in the spinal cord, facial nucleus, pontine gray, red nucleus, putamen, and primary and supplementary motor cortices, we suggest that the cingulate motor cortex forms a strategic cortical entry point for limbic influence on the voluntary motor system.     

Cingulate cortex of the rhesus monkey: II. Cortical afferents

Cortical projections to subdivisions of the cingulate cortex in the rhesus monkey were analyzed with horseradish peroxidase and tritiated amino acid tracers. These projections were evaluated in terms of an expanded cytoarchitectural scheme in which areas 24 and 23 were divided into three ventrodorsal parts, i.e., areas 24a-c and 23a-c. Most cortical input to area 25 originated in the frontal lobe in lateral areas 46 and 9 and orbitofrontal areas 11 and 14. Area 25 also received afferents from cingulate areas 24b, 24c, and 23b, from rostral auditory association areas TS2 and TS3, from the subiculum and CA1 sector of the hippocampus, and from the lateral and accessory basal nuclei of the amygdala (LB and AB, respectively). Areas 24a and 24b received afferents from areas 25 and 23b of cingulate cortex, but most were from frontal and temporal cortices. These included the following areas: frontal areas 9, 11, 12, 13, and 46; temporal polar area TG as well as LB and AB; superior temporal sulcus area TPO; agranular insular cortex; posterior parahippocampal cortex including areas TF, TL, and TH and the subiculum. Autoradiographic cases indicated that area 24c received input from the insula, parietal areas PG and PGm, area TG of the temporal pole, and frontal areas 12 and 46. Additionally, caudal area 24 was the recipient of area PG input but not amygdalar afferents. It was also the primary site of areas TF, TL, and TH projections. The following projections were observed both to and within posterior cingulate cortex. Area 29a-c received inputs from area 46 of the frontal lobe and the subiculum and in turn it projected to area 30. Area 30 had afferents from the posterior parietal cortex (area Opt) and temporal area TF. Areas 23a and 23b received inputs mainly from frontal areas 46, 9, 11, and 14, parietal areas Opt and PGm, area TPO of superior temporal cortex, and areas TH, TL, and TF. Anterior cingulate areas 24a and 24b and posterior areas 29d and 30 projected to area 23. Finally, a rostromedial part of visual association area 19 also projected to area 23. The origin and termination of these connections were expressed in a number of different laminar patterns. Most corticocortical connections arose in layer III and to a lesser extent layer V, while others, e.g., those from the cortex of the superior temporal sulcus, had an equal density of cells in both layers III and V.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.     

Cortical efferents of the entorhinal cortex and the adjacent parahippocampal region in the monkey (Macaca fascicularis)

Entorhinal cortex (EC) relays information from the hippocampus to the cerebral cortex. The origin of this entorhino-cortical pathway was studied semiquantitatively and topographically with the use of 23 retrograde tracer injections in cortical areas of the frontal, temporal, and parietal lobes of the monkey. To assess possible alternative, parallel pathways, the parahippocampal region, comprised of temporal pole (TP), perirhinal (PRC), and posterior parahippocampal cortices (PPH), was included in the study. The majority of the cortical areas receive convergent projections from EC and the parahippocampal region. Strong EC layer V output is directed to temporal pole, medial frontal and orbitofrontal cortices, and the rostral part of the polysensory area of the superior temporal sulcus (sts). Moderate EC output is directed to the caudal superior temporal gyrus, area TE, and parietal cortex, and little to none to the lateral frontal cortex. With the exception of the projection to the medial frontal cortex, output from TP, PRC, and PPH surpassed that from EC, although with regional differences. TP layers II-III, V-VI project strongly to all areas injected except parietal cortex and caudal superior temporal gyrus, while PRC layers III/V-VI send strong projections to rostral parts of area TE and sts. PPH layers III/V-VI project heavily to parietal cortex and caudal superior temporal gyrus. These results suggest that the medial temporal output is primarily organized hierarchically, but at the same time, it has multiple exits of information. These parallel, alternative routes may influence local circuitry in the cerebral cortex and participate in the consolidation of declarative memory.     

Efferent connections of the orbitofrontal cortex in the marmoset(Saguinus oedipus)

Unilateral partial ablations were made in the orbitofrontal cortex of 4 adult marmosets(Saguinus oedipus) and fiber degeneration was traced using the Nauta-Gygax and Fink-Heimer selective silver impregnation techniques. Corticocortical projections were found to the ipsilateral convexity and medial aspect of the frontal lobe and to the homologous orbitofrontal areas of the contralateral hemisphere. Fiber degeneration was followed through the uncinate fascicle to the temporal and insular cortices, and caudally into the rostrolateral entorhinal cortex. Other fibers joined the cingulum bundle and terminated throughout the cingulate cortex.Subcortical projections were observed to the lateral and basal amygdaloid nuclei, caudate head, ventrolateral putamen and ventral claustrum. The lateral preoptic and hypothalamic areas received a small number of fibers, as did the intralaminar and reticular thalamic nuclei. The dorsomedial nucleus of the thalamus was recipient of a large group of fibers which followed the ventral internal capsule and joined the inferior thalamic peduncle to terminate there. Preterminal debris appeared heaviest in the dorsomedial thalamic nucleus, pars magnocellularis (MDmc) in more caudal orbital lesions. A subthalamic projection to field H of Forel was observed. A small number of fibers terminated in the lateral midbrain tegmentum, but no appreciable fiber degeneration was observed more caudally than the midbrain. These results are compared in some areas to findings in the rhesus monkey. The possibility of a topical organization in the orbital cortical and thalamic projections is discussed.     

Macaque monkey retrosplenial cortex: III. Cortical efferents

We have investigated the cortical efferent projections of the macaque monkey retrosplenial and posterior cingulate cortices by using (3)H-amino acids as anterograde tracers. All the injections produced extensive local connections to other portions of this region. There were also a number of extrinsic efferent cortical connections, many of which have not hitherto been reported. Major projections from the retrosplenial cortex were directed to the frontal lobe, with heaviest terminations in areas 46, 9, 10, and 11. There were also very substantial projections to the entorhinal cortex, presubiculum, and parasubiculum of the hippocampal formation, as well as to areas TH and TF of the parahippocampal cortex. Some injections led to labeling of area V4, the dorsal bank of the superior temporal sulcus, and area 7a of the parietal cortex. Projections from the posterior cingulate cortex innervated all these same regions, although the density of termination was different from the retrosplenial projections. The posterior cingulate cortex gave rise to additional projections to parietal area DP and to the cortex along the convexity of the superior temporal gyrus. The ventral portion of the posterior cingulate cortex (area 23v) gave rise to much denser efferent projections to the hippocampal formation than the dorsal portions (areas 23e and i). These connections are discussed in relation to the clinical syndromes of retrosplenial amnesia and topographic disorientation in humans commonly caused by lesions in the caudoventral portions of the retrosplenial and posterior cingulate cortices.