Orbital And Medial Prefrontal Cortex Research Articles

Decreased cortical thickness of left premotor cortex as a treatment predictor in major depressive disorder.

This study aimed to examine the cerebral cortex characteristics (thickness, surface area, and curvature) in patients with major depressive disorder (MDD), and explore whether these cortex characteristics are predictors for the antidepressant therapeutic effect. 105 patients with MDD and 49 healthy controls (HCs) were recruited. Both groups were given magnetic resonance image (MRI) scans at baseline period, and then the cerebral cortex characteristics (thickness, surface area, and curvature) were calculated using the DPABISurf software. The Hamilton Depression Scale-24 (HAMD-24) reductive rate was used to measure antidepressant therapeutic effect and Snaith Hamilton Rating Scale (SHAPS) reduction was performed to assess the change of anhedonia after treatment of 8 weeks. Correlation analysis was performed to identify the relationship between cortex characteristics and antidepressant therapeutic effect in patients with MDD. There were no significant differences in the cortical curvature and surface area between MDD and HC groups, while significant decreases were found in the cortical thickness of inferior frontal cortex (IFC), premotor cortex (PMC), orbital and medial prefrontal cortex (OMPFC) in the left hemisphere of MDD group, comparing with HC group (P < 0.05 for all, corrected by threshold-free cluster enhancement). In MDD group, the cortical thickness of left PMC had significant positive correlations with 8-week HAMD-24 reduction (r = 0.228, P = 0.020) and HAMD-24 reductive rate (r = 0.193, P = 0.048); and a negative correlation with the 8-week SHAPS reduction (r = -0.240, P = 0.018). Decreased cortical thickness in left PMC may be a predictor of therapeutic effect in MDD. Determining the cortical thickness of this region before treatment can provide certain reference value for clinical antidepressant treatment.

Human orbital and anterior medial prefrontal cortex: Intrinsic connectivity parcellation and functional organization

The orbital and medial prefrontal cortex (OMPFC) has been implicated in decision-making, reward and emotion processing, and psychopathology, such as depression and obsessive–compulsive disorder. Human and monkey anatomical studies indicate the presence of various cortical subdivisions and suggest that these are organized in two extended networks, a medial and an orbital one. Attempts have been made to replicate these neuroanatomical findings in vivo using MRI techniques for imaging connectivity. These revealed several consistencies, but also many inconsistencies between reported results. Here, we use fMRI resting-state functional connectivity (FC) and data-driven modularity optimization to parcellate the OMPFC to investigate replicability of in vivo parcellation more systematically. By collecting two resting-state data sets per participant, we were able to quantify the reliability of the observed modules and their boundaries. Results show that there was significantly more than chance overlap in modules and their boundaries at the level of individual data sets. Moreover, some of these consistent boundaries significantly co-localized across participants. Hierarchical clustering showed that the whole-brain FC profiles of the OMPFC subregions separate them in two networks, a medial and orbital one, which overlap with the organization proposed by Barbas and Pandya (J Comp Neurol 286:353–375, 1989) and Ongür and Price (Cereb Cortex 10:206–219, 2000). We conclude that in vivo resting-state FC can delineate reliable and neuroanatomically plausible subdivisions that agree with established cytoarchitectonic trends and connectivity patterns, while other subdivisions do not show the same consistency across data sets and studies.

An Increase in Tobacco Craving Is Associated with Enhanced Medial Prefrontal Cortex Network Coupling

Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI) in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC) network, which also included the subgenual anterior cingulate cortex (sgACC) extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving.

The Influence of "Hot" Executive Function on the Verbal Working Memory of Attention Deficit Hyperactivity Disorder (ADHD) and Reading Disability (RD) Children

The deficit of "cool" executive function (EF) associated with dorsolateral prefrontal cortex (DLPFC) in attention deficit hyperactivity disorder (ADHD) has been substantially confirmed. But whether ADHD children show the deficit of "hot" EF associated with orbital and medial prefrontal cortex (OMPFC) remains unknown, and till now no research made an explicit exploration for interaction models between the two EFs. Commonly different from some studies related to the children’s gambling task, in which the "hot" EF impeded "cool" EF, this study aims to explore the facilitation of the "hot" EF to "cold" EF in the entertaining verbal N-back task. Pure cognitive processions were involved in boring N-back task while both "hot" EF and "cold" EF were involved in the entertaining N-back task. Participants were 77 children age between seven and twelve, of whom 60 were classified as having ADHD and /or reading disability (RD). All the disorder participants were recruited at a clinic and normal children were recruited from a elementary school. A four-group mixed design consisting of reading disabilities only (RD, n=15), reading disabilities and ADHD (RD+ADHD, n=24), ADHD only (ADHD, n=21) and a comparison group (n=17) was utilized. In the experiment, two adapted N-back working memory paradigms were used to explore verbal working memory ability, one was a traditional N-back task, another was entertaining N-back task. There are the same difficulty and materials between the two tasks. The results indicate that ADHD and RD groups behaved worse than comparison group and no significant differences had been detected between ADHD and RD groups in the boring task. A significant increase in ADHD had been found when comparing entertaining task with boring task. No significant differences had been detected between ADHD and comparison groups. Also, no significant changes related to the task types had been found in RD children. All these findings suggest that ADHD and RD children both show verbal working memory problems, however they have different mechanisms. The "hot" EF facilitates the performance of ADHD in verbal working memory task while not to RD. These results support the Haber model indirectly. According to this model, "hot" EF modulates "cool" EF by a special pathway.

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

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

Midline and intralaminar thalamic connections with the orbital and medial prefrontal networks in macaque monkeys

Although the midline and intralaminar thalamic nuclei (MITN) were long believed to project "nonspecifically," they are now known from rat studies to have restricted connections to the prefrontal cortex. This has not been studied thoroughly in primates, however, and it is not known how MITN are associated with the "orbital" and "medial" prefrontal networks. This study examined the connections of MITN in cynomolgus monkeys (Macaca fascicularis). Experiments with retrograde and anterograde tracer injections into the orbital and medial prefrontal cortex (OMPFC) showed that MITN are strongly connected with the medial prefrontal network. The dorsal nuclei of the midline thalamus, including the paraventricular (Pa) and parataenial nuclei (Pt), had heavy connections with medial network areas 25, 32, and 14c in the subgenual region. Areas 13a and 12o, which are associated with both networks, were strongly connected with the Pt and the central intermedial nucleus, respectively. Otherwise, orbital network areas had weak connections with MITN. Anterograde tracer injections into the dorsal midline thalamus resulted in heavy terminal labeling in the medial prefrontal network, most notably in areas ventral to the genu of the corpus callosum (25, 32, and 14c), but also in adjacent areas (13a and 13b). Retrograde tracer injection into the dorsal midline labeled similar areas. The medial network, particularly the subgenual region, is involved in visceral and emotional control and has been implicated in mood disorders. The strong connections between the subgenual cortex and the Pa provide a pathway through which stress signals from the Pa may influence these prefrontal circuits.

Differential connections of the perirhinal and parahippocampal cortex with the orbital and medial prefrontal networks in macaque monkeys

Previous anatomical studies indicate that the orbital and medial prefrontal cortex (OMPFC) of monkeys is organized into an "orbital" network, which appears to be related to feeding and reward, and a "medial" network, related to visceral control and emotion. In this study, we examined the connections of the orbital and medial prefrontal networks with the perirhinal (areas 35 and 36) and parahippocampal (areas TF and TH) cortex with anterograde and retrograde axonal tracers. The perirhinal cortex is reciprocally connected with orbital network areas Iapm, Iam, Ial, 13m, 13l, 12r, and 11l. In contrast, the parahippocampal cortex is reciprocally connected with the medial network, especially areas around the corpus callosum (areas 24a/b, caudal 32, and 25), and with area 11m. Projections from the parahippocampal cortex also extend to areas 10m, 10o, Iai, and rostral area 32, as well as to dorsolateral areas 9 and 46. In addition, both the perirhinal and parahippocampal cortex are reciprocally connected with areas that are intermediate between the orbital and medial networks (areas 13a, 13b, and 14c) and with the supracallosal area 24a'/b'. Outside the frontal cortex, the perirhinal cortex and the orbital prefrontal network are both interconnected with the ventral part of the temporal pole (TG), area TE and the ventral bank and fundus of the superior temporal sulcus (STS), and the dysgranular insula. In contrast, the parahippocampal cortex and the medial prefrontal network are connected with the dorsal TG, the rostral superior temporal gyrus (STG) and dorsal bank of STS, and the retrosplenial cortex.

Convergence and Interaction of Hippocampal and Amygdalar Projections within the Prefrontal Cortex in the Rat

The orbital and medial prefrontal cortex (OMPFC) receives inputs from the CA1/subicular (CA1/S) region of the ventral hippocampus and the basolateral nucleus of the amygdala (BLA). Despite many studies about these projections, little is known as to how CA1/S and BLA inputs converge and interact within the OMPFC. Extracellular recordings of single-unit activity in the OMPFC were performed in sodium pentobarbitone-anesthetized rats. OMPFC neurons driven by CA1/S or BLA stimulation were more frequently encountered in the ventral portion of the prelimbic (v-PrL) and infralimbic cortex (IL). OMPFC neurons showing excitatory convergence of both inputs from the CA1/S and BLA were also located predominantly in the v-PrL and IL. The excitatory latencies of these neurons from both the CA1/S and BLA revealed almost identical values. Excitatory responses of OMPFC neurons to CA1/S (or BLA) stimulation were markedly augmented by simultaneous BLA (or CA1/S) stimulation, whereas the inhibitory influence of the BLA (or CA1/S) on CA1/S-induced (or BLA-induced) excitation was apparent when BLA (or CA1/S) stimulation was given 20-40 msec before CA1/S (or BLA) stimulation. Similar results were also observed when reciprocal connections between the CA1/S and BLA were severed to exclude the influences of these connections on one another. From these studies, we concluded that excitatory and inhibitory inputs from the hippocampus and amygdala converge and interact in the v-PrL and IL. Furthermore, the results indicate that simultaneous activation of hippocampal and amygdalar neurons may be important for amplification of OMPFC neuronal activity.

Architectonic subdivision of the human orbital and medial prefrontal cortex.

The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price (1994) J. Comp. Neurol. 346:366-402]. A cortical area was recognized if it was distinct with at least two stains and was found in similar locations in different brains. All of the areas recognized in the macaque OMPFC have counterparts in humans. Areas 11, 13, and 14 were subdivided into areas 11m, 11l, 13a, 13b, 13m, 13l, 14r, and 14c. Within area 10, the region corresponding to area 10m in monkeys was divided into 10m and 10r, and area 10o (orbital) was renamed area 10p (polar). Areas 47/12r, 47/12m, 47/12l, and 47/12s occupy the lateral orbital cortex, corresponding to monkey areas 12r, 12m, 12l, and 12o. The agranular insula (areas Iam, Iapm, Iai, and Ial) extends onto the caudal orbital surface and into the horizontal ramus of the lateral sulcus. The growth of the frontal pole in humans has pushed area 25 and area 32pl, which corresponds to the prelimbic area 32 in Brodmann's monkey brain map, caudal and ventral to the genu of the corpus callosum. Anterior cingulate areas 24a and 24b also extend ventral to the genu of the corpus callosum. Area 32ac, corresponding to the dorsal anterior cingulate area 32 in Brodmann's human brain map, is anterior and dorsal to the genu. The parallel organization of the OMPFC in monkeys and humans allows experimental data from monkeys to be applied to studies of the human cortex.

The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans.

This paper reviews architectonic subdivisions and connections of the orbital and medial prefrontal cortex (OMPFC) in rats, monkeys and humans. Cortico-cortical connections provide the basis for recognition of 'medial' and 'orbital' networks within the OMPFC. These networks also have distinct connections with structures in other parts of the brain. The orbital network receives sensory inputs from several modalities, including olfaction, taste, visceral afferents, somatic sensation and vision, which appear to be especially related to food or eating. In contrast, the medial network provides the major cortical output to visceromotor structures in the hypothalamus and brainstem. The two networks have distinct connections with areas of the striatum and mediodorsal thalamus. In particular, projections to the nucleus accumbens and the adjacent ventromedial caudate and putamen arise predominantly from the medial network. Both networks also have extensive connections with limbic structures. Based on these and other observations, the OMPFC appears to function as a sensory-visceromotor link, especially for eating. This linkage appears to be critical for the guidance of reward-related behavior and for setting of mood. Imaging and histological observations on human brains indicate that clinical depressive disorders are associated with specific functional and cellular changes in the OMPFC, including activity and volume changes, and specific changes in the number of glial cells.

Prefrontal cortical networks related to visceral function and mood.

At least twenty-two architectonic areas can be distinguished within the orbital and medial prefrontal cortex (OMPFC). Although each of these areas has a distinct structure and connections, they can be grouped into two "networks," defined by cortico-cortical connections that primarily interconnect areas within each network. The networks also have different connections to the striatum, medial thalamus, and other brain regions. The orbital network consists of most of the areas in the orbital cortex. It receives several sensory inputs (olfactory, gustatory, visceral afferent, somatic sensory, and visual) that appear to be related to feeding. It also receives many limbic inputs from the amygdala, entorhinal and perirhinal cortex, and subiculum, including a specific projection from the ventrolateral part of the basal amygdaloid nucleus. The orbital network may therefore serve as a substrate to integrate viscerosensory information with affective signals. The medial network consists of areas on the medial frontal surface together with a few select areas in the orbital cortex. These areas have few direct sensory inputs, and their limbic inputs are somewhat different than those to the orbital network (e.g., from the ventromedial part of the basal amygdaloid nucleus). However, they provide the major output from the OMPFC to the hypothalamus and brain stem (especially the periaqueductal gray). The medial network may therefore serve as a visceromotor system to provide frontal cortical influence over autonomic and endocrine function. Connections between the networks presumably allow information flow from viscerosensory to visceromotor systems. In addition to a probable role in eating behavior, this system appears to be involved in guiding behavior and regulation of mood. Lesions of the ventromedial prefrontal cortex result in sociopathic behavior and difficulty in making appropriate choices, whereas functional imaging studies indicate that subjects with unipolar and bipolar depression have abnormal activity in medial and orbital prefrontal areas. Many of these areas also show volume changes and decreased glial number and density in mood-disordered subjects.

Prefrontal cortical projections to the hypothalamus in Macaque monkeys

The organization of projections from the macaque orbital and medial prefrontal cortex (OMPFC) to the hypothalamus and related regions of the diencephalon and midbrain was studied with retrograde and anterograde tracing techniques. Almost all of the prefrontal cortical projections to the hypothalamus arise from areas within the “medial prefrontal network,” as defined previously by Carmichael and Price ([1996] J. Comp. Neurol. 371:179–207). Outside of the OMPFC, only a few neurons in the temporal pole, anterior cingulate and insular cortex project to the hypothalamus. Axons from the OMPFC also innervate the basal forebrain, zona incerta, and ventral midbrain. Within the medial prefrontal network, different regions project to distinct parts of the hypothalamus. The medial wall areas 25 and 32 send the heaviest projections to the hypothalamus; axons from these areas are especially concentrated in the anterior hypothalamic area and the ventromedial hypothalamic nucleus. Orbital areas 13a, 12o, and Iai, which are related to the medial prefrontal network, selectively innervate the lateral hypothalamic area, especially its posterior part. The cellular regions of the paraventricular, supraoptic, suprachiasmatic, arcuate, and mammillary nuclei are conspicuously devoid of cortical axons, but many axons abut the borders of these nuclei and may contact dendrites that extend from them. Areas within the orbital prefrontal network on the posterior orbital surface and agranular insula send only weak projections to the posterior lateral hypothalamic area. The rostral orbital surface does not contribute to the cortico-hypothalamic projection. J. Comp. Neurol. 401:480–505, 1998. © 1998 Wiley-Liss, Inc.

Prefrontal cortical projections to the hypothalamus in Macaque monkeys

The organization of projections from the macaque orbital and medial prefrontal cortex (OMPFC) to the hypothalamus and related regions of the diencephalon and midbrain was studied with retrograde and anterograde tracing techniques. Almost all of the prefrontal cortical projections to the hypothalamus arise from areas within the "medial prefrontal network," as defined previously by Carmichael and Price ([1996] J. Comp. Neurol. 371:179-207). Outside of the OMPFC, only a few neurons in the temporal pole, anterior cingulate and insular cortex project to the hypothalamus. Axons from the OMPFC also innervate the basal forebrain, zona incerta, and ventral midbrain. Within the medial prefrontal network, different regions project to distinct parts of the hypothalamus. The medial wall areas 25 and 32 send the heaviest projections to the hypothalamus; axons from these areas are especially concentrated in the anterior hypothalamic area and the ventromedial hypothalamic nucleus. Orbital areas 13a, 12o, and Iai, which are related to the medial prefrontal network, selectively innervate the lateral hypothalamic area, especially its posterior part. The cellular regions of the paraventricular, supraoptic, suprachiasmatic, arcuate, and mammillary nuclei are conspicuously devoid of cortical axons, but many axons abut the borders of these nuclei and may contact dendrites that extend from them. Areas within the orbital prefrontal network on the posterior orbital surface and agranular insula send only weak projections to the posterior lateral hypothalamic area. The rostral orbital surface does not contribute to the cortico-hypothalamic projection.

Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys

The intrinsic cortico-cortical connections within the orbital and medial prefrontal cortex (OMPFC) were demonstrated with retrograde and anterograde tracers injected into each of the architectonic areas that constitute this region. Although many of the connections linked neighboring areas, others selectively connected relatively distant areas. Most, but not all, of the connections were reciprocal. Altogether, the connections formed at least two distinct networks within the OMPFC. The "orbital" prefrontal network linked most of the areas within the orbital cortex, with very few connections to medial prefrontal areas. Areas Iam, Iapm, Ial, 12l, 12m, and 12r in the caudal and lateral parts of the orbital cortex (which received inputs from several sensory modalities) had convergent connections with areas 13l, 13m, and 13b in the central orbital cortex, with further connections to the rostral orbital area 11l. For the connections between areas Iapm, Iam, Ial, 13m, 13l, and 11l, rostrally directed fibers arose mainly in layer V, whereas caudally directed fibers originated mainly in layer III. The "medial" prefrontal network selectively involved medial areas 14r, 14c, 24, 25, 32, and 10m, rostral orbital areas 10o and 11m, and agranular insular area Iai in the posterior orbital cortex. Two orbital areas, 13a and 12o, had substantial connections to both networks and may serve as points of interaction between them; otherwise there were relatively few interconnections. The two networks also had distinct connections with other cortical regions, with limbic structures, and with the mediodorsal thalamic nucleus. Their role in guidance of affective behaviour is discussed.

Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys

The intrinsic cortico-cortical connections within the orbital and medial prefrontal cortex (OMPFC) were demonstrated with retrograde and anterograde tracers injected into each of the architectonic areas that constitute this region. Although many of the connections linked neighboring areas, others selectively connected relatively distant areas. Most, but not all, of the connections were reciprocal. Altogether, the connections formed at least two distinct networks within the OMPFC. The "orbital" prefrontal network linked most of the areas within the orbital cortex, with very few connections to medial prefrontal areas. Areas Iam, Iapm, Ial, 12l, 12m, and 12r in the caudal and lateral parts of the orbital cortex (which received inputs from several sensory modalities) had convergent connections with areas 13l, 13m, and 13b in the central orbital cortex, with further connections to the rostral orbital area 11l. For the connections between areas Iapm, Iam, Ial, 13m, 13l, and 11l, rostrally directed fibers arose mainly in layer V, whereas caudally directed fibers originated mainly in layer III. The "medial" prefrontal network selectively involved medial areas 14r, 14c, 24, 25, 32, and 10m, rostral orbital areas 10o and 11m, and agranular insular area Iai in the posterior orbital cortex. Two orbital areas, 13a and 12o, had substantial connections to both networks and may serve as points of interaction between them; otherwise there were relatively few interconnections. The two networks also had distinct connections with other cortical regions, with limbic structures, and with the mediodorsal thalamic nucleus. Their role in guidance of affective behaviour is discussed.

Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys

Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers. Restricted areas of the lateral and posterior orbital cortex had specific connections with visual-, somatosensory-, olfactory-, gustatory-, and visceral-related structures. More medial areas received few direct sensory inputs. Within the lateral and posterior orbital cortex, area 12l received a substantial projection from visual areas in the inferior temporal cortex (TE). Area 12m received somatosensory input from face, digit, or forelimb regions in the opercular part of area 1-2, in area 7b, in the second somatosensory area (SII), and in the anterior infraparietal area (AIP). Areas 13m and 13l also received a projection from the opercular part of areas 1-2 and 3b. The posteromedial and lateral agranular insular areas (Iapm and Ial, respectively) received fibers from the ventral part of the parvicellular division of the ventroposterior medial nucleus of the thalamus (VPMpc) that may represent a visceral afferent system. The dorsal part of VPMpc projected to the adjacent gustatory cortex. These restricted inputs from several sensory modalities and the convergent corticocortical connections to orbital areas 13l and 13m suggest a network related to feeding. The OMPFC was also connected to premotor cortex in ventral area 6 (areas 6va and 6vb), in cingulate area 24c, and probably in the supplementary eye field. Area 6va projected to area 12m, whereas a region of area 6vb projected to area 13l. The region of the supplementary eye field projected to areas 12l, 12o, and 12r. Area Ial received fibers from area 24c. Lighter and more diffuse projections also reached wider areas of the OMPFC. For example, injections in several orbital areas labeled a few cells scattered through the anterior part of area TE and the superior temporal gyrus. There was also a projection to the intermediate agranular insular area (Iai) and to areas 13a and 12o from the apparently multimodal areas in the superior temporal sulcus and gyrus.

Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys.

Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 12l; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for area Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 12o, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m.