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.     

Frontal-subcortical circuitry and behavior

The neuropsychiatric manifestations of neurodegenerative diseases are closely linked to neurocircuitry defects. Frontal-subcortical circuits, in particular, are effector mechanisms that allow the organism to act on its environment. In this paper, we present the three main frontal-subcortical circuits: the dorsolateral prefrontal circuit allows the organization of information to facilitate a response; the anterior cingulate circuit is required for motivated behavior; and the orbitofrontal circuit allows the integration of limbic and emotional information into behavioral responses. Impaired executive functions, apathy, and impulsivity are hallmarks of frontal-subcortical circuit dysfunction. A variety of other neuropsychiatric disorders, such as Tourette's syndrome, Huntington's disease, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, schizophrenia, and mood disorders may result from disturbances that have a direct or indirect impact on the integrity or functioning of these loops.     

Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.     

Representation of attitudinal knowledge: role of prefrontal cortex, amygdala and parahippocampal gyrus

It has been proposed that behavior is influenced by representations of different types of knowledge: action representations, event knowledge, attitudes and stereotypes. Attitudes (representations of a concept or object and its emotional evaluation) allow us to respond quickly to a given stimulus. In this study, we explored the representation and inhibition of attitudes. We show that right dorsolateral prefrontal cortex mediates negative attitudes whereas left ventrolateral prefrontal cortex mediates positive attitudes. Parahippocampal regions and amygdala mediate evaluative processing. Furthermore, anxiety modulates right dorsolateral prefrontal activation during negative attitude processing. Inhibition of negative attitudes activates left orbitofrontal cortex: a region that when damaged is associated with socially inappropriate behavior in patients. Inhibition of positive attitudes activates a brain system involving right inferior frontal gyrus and bilateral anterior cingulate. Thus, we show that there are dissociable networks for the representation and inhibition of attitudes.     

Local gyrification index in patients with major depressive disorder and its association with tryptophan hydroxylase‐2 (TPH2) polymorphism

The tryptophan hydroxylase‐2 (TPH2) gene is considered a promising genetic candidate regarding its association with a predisposition to major depressive disorder (MDD). Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. They aimed to investigate the alterations in the cortical gyrification of the prefrontal cortex and anterior cingulate cortex and their association with the TPH2 rs4570625 polymorphism in patients with MDD. One hundred and thirteen patients with MDD and eighty‐six healthy controls underwent T1‐weighted structural magnetic resonance imaging and genotyping for TPH2 rs4570625. The local gyrification index of 22 cortical regions in the prefrontal cortex and anterior cingulate cortex was analyzed using the FreeSurfer. The patients with MDD showed significant hypergyria in the right rostral anterior cingulate cortex (P = 0.001), medial orbitofrontal cortex (P = 0.003), and frontal pole (P = 0.001). There was a significant genotype‐by‐diagnosis interaction for the local gyrification index in the right rostral anterior cingulate cortex (P = 0.003). Their study revealed significant hypergyria of the anterior cingulate cortex and prefrontal cortex and an interactive effect between the diagnosis of MDD and the genotype in the anterior cingulate cortex. This might be associated with the dysfunction of neural circuits mediating emotion processing, which could contribute to pathophysiology of MDD. Hum Brain Mapp 38:1299–1310, 2017. © 2016 Wiley Periodicals, Inc.     

Heterotopic Cortical Afferents to the Medial Prefrontal Cortex in the Rat. A Combined Retrograde and Anterograde Tracer Study

Cortical afferent projections towards the medial prefrontal cortex (mPFC) were investigated with retrograde and anterograde tracer techniques. Heterotopical afferent projections to the medial prefrontal cortex arise in secondary, or higher order, sensory areas, motor areas and paralimbic cortices. On the basis of these projections three subfields can be discriminated within the mPFC. (1) The ventromedial part of mPFC, comprising the pre- and infralimbic areas, receives mainly projections from the perirhinal cortex. (2) The caudal two-thirds of the dorsomedial PFC, comprising frontal area 2 and the dorsal anterior cingulate area, receives projections from the secondary visual areas, the posterior agranular insular area and the retrosplenial areas. (3) The rostral one-third of the dorsomedial PFC is the main recipient of projections from the somatosensory and motor areas and the posterior agranular insular area. The laminar distribution of cells projecting to the mPFC varies considerably in the different cortical areas, just as the laminar distribution of termination of their fibres within the mPFC does. It is concluded that the corticocortical connections corroborate with subcortical connectivity in attributing to the mediodorsal projection cortex of the rat functions which are comparable to those of certain prefrontal, premotor and anterior cingulate areas in the monkey.     

Disorders of voluntary motor activity and lesions of caudate nuclei

Three clinical cases are reported, resulting in apathy, uninterest, flattened affect and lack of initiative for usual daily activities. Intellectual performances were normal and there was no depression. This syndrome was reversible when patients were stimulated. Stereotyped behaviors resembling compulsions were frequent. One of the patients presented with prolonged akinetic episodes reversible by verbal stimulation. CT and MRI showed bilateral lesions, mainly in and around the head of the caudate nucleus. Such behavioral disorders have been termed psychic akinesia or athymhormia syndrome, suggesting that the patients suffered from a loss of drive and motivation. The lesions involved bilaterally the globus pallidus, the striatum or the frontal lobe. Recently, anatomical findings have shown several circuits through the basal ganglia additional to the motor circuit. The caudate nucleus receives inputs from the prefrontal and limbic cortex. These inputs are transmitted to the globus pallidus, then to the thalamus and ultimately return to the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate areas. Lesions in any part of these cortico-subcortical loops may be responsible for a dramatic behavioral syndrome, emphasizing their functional specificity in drive. However, a procedural learning impairment in neostriatal dysfunction could possibly explain the disorders observed in our patients.     

The role of intact frontostriatal circuits in error processing

The basal ganglia have been suggested to play a key role in performance monitoring and resulting behavioral adjustments. It is assumed that the integration of prefrontal and motor cortico-striato-thalamo-cortical circuits provides contextual information to the motor anterior cingulate cortex regions to enable their function in performance monitoring. So far, direct evidence is missing, however. We addressed the involvement of frontostriatal circuits in performance monitoring by collecting event-related brain potentials (ERPs) and behavioral data in nine patients with focal basal ganglia lesions and seven patients with lateral prefrontal cortex lesions while they performed a flanker task. In both patient groups, the amplitude of the error-related negativity was reduced, diminishing the difference to the ERPs on correct responses. Despite these electrophysiological abnormalities, most of the patients were able to correct errors. Only in lateral prefrontal cortex patients whose lesions extended into the frontal white matter, disrupting the connections to the motor anterior cingulate cortex and the striatum, were error corrections severely impaired. In sum, the fronto-striato-thalamo-cortical circuits seem necessary for the generation of error-related negativity, even when brain plasticity has resulted in behavioral compensation of the damage. Thus, error-related ERPs in patients provide a sensitive measure of the integrity of the performance monitoring network.     

Cerebral blood flow in the ventromedial prefrontal cortex correlates with treatment response to low-frequency right prefrontal repetitive transcranial magnetic stimulation in the treatment of depression

Aims: Low‐frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, and its antidepressant effects have proven to correlate with decreases in cerebral blood flow (CBF) in the orbitofrontal cortex and subgenual cingulate cortex. However, a predictor of treatment response to low‐frequency right prefrontal rTMS in depression has not been identified yet. The aim of this study was to estimate regional CBF in the frontal regions and investigate the correlation with treatment response to low‐frequency right prefrontal rTMS in depression. Methods: We examined 26 depressed patients for the correlation between treatment response to rTMS and regional CBF in the frontal regions, by analyzing their brain scans with ^99mTc‐ethyl cysteinate dimer before rTMS treatment. CBF in 16 brain regions was estimated using fully automated region of interest analysis software. Two principal components were extracted from CBF in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. Results: Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions) and ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was not correlated with CBF in the dorsolateral prefrontal cortex, but it was correlated with CBF in the ventromedial prefrontal cortex. Conclusion: These findings suggest that CBF in the ventromedial prefrontal cortex may be a potential predictor of low‐frequency right prefrontal rTMS, and depressed patients with increased CBF in the ventromedial prefrontal cortex may show a better response.     

Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity

Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input.     

Error detection in patients with lesions to the medial prefrontal cortex: an ERP study

When people detect their own errors in a discrimination task, a negative-going waveform can be observed in scalp-recorded EEG that has been coined the error-related negativity (Ne/ERN). Generation of the Ne/ERN has been associated with structures in the prefrontal cortex, especially the anterior cingulate region, but also the supplementary motor cortex and subcortical structures. There is some controversy as to whether the Ne/ERN is a necessary concomitant to error detection. We examined the Ne/ERN in five patients with damage to the medial prefrontal cortex, including the anterior cingulate region. Our findings support the implication of the rostral anterior cingulate in Ne/ERN production, but they also show that subjects can be aware of errors and yet not produce an Ne/ERN. Thus, error detection leads to the Ne/ERN process and damage to the anterior cingulate region may interrupt this relay, suggesting that error detection may be supported by circuits outside the anterior cingulate region.     

Involvement of rat posterior prelimbic and cingulate area 2 in vocalization control

Microstimulation mapping identified vocalization areas in primate anterior cingulate cortex. Rat anterior cingulate and medial prefrontal areas have also been intensely investigated, but we do not know, how these cortical areas contribute to vocalizations and no systematic mapping of stimulation‐evoked vocalizations has been performed. To address this question, we mapped microstimulation‐evoked (ultrasonic) vocalizations in rat cingulate and medial prefrontal cortex. The incidence of evoked vocalizations differed markedly between frontal cortical areas. Vocalizations were most often evoked in posterior prelimbic cortex and cingulate area 2, whereas vocalizations were rarely evoked in dorsal areas (vibrissa motor cortex, secondary motor cortex and cingulate area 1) and anterior areas (anterior prelimbic, medial‐/ventral‐orbital cortex). Vocalizations were observed at intermediate frequencies in ventro‐medial areas (infralimbic and dorsopeduncular cortex). Various complete, naturally occurring calls could be elicited. In prelimbic cortex superficial layer microstimulation evoked mainly fear calls with low efficacy, whereas deep layer microstimulation evoked mainly 50 kHz calls with high efficacy. Vocalization stimulation thresholds were substantial (70–500 μA, the maximum tested; on average ~400 μA) and latencies were long (median 175 ms). Posterior prelimbic cortex projected to numerous targets and innervated brainstem vocalization centers such as the intermediate reticular formation and the nucleus retroambiguus disynaptically via the periaqueductal gray. Anatomical position, stimulation effects and projection targets of posterior prelimbic cortex were similar to that of monkey anterior cingulate vocalization cortex. Our data suggest that posterior prelimbic cortex is more closely involved in control of vocalization initiation than in specifying acoustic details of vocalizations.     

Cytoarchitecture and cortical connections of the anterior cingulate and adjacent somatomotor fields in the rhesus monkey

The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining methods and the fluorescent retrograde tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presence of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity mediate voluntary motor function, their close connectional relationship with the cingulate areas form a pivotal limbic-motor interface that could provide critical sources of cognitive, emotional and motivational influence on complex motor function.     

Subcortical infarcts (caudate nucleus) in a case of bilateral anterior cerebral artery occlusion]

The authors describe a patient with bilateral anterior cerebral artery (ACA) occlusion. CT and MRI revealed bilateral encephalomalacia in the regions supplied by Heubner arteries and/or by perforating branches of ACA. The patient presented mainly with frontal symptomatology resulting from caudate nuclei lesion. Frontal symptomatology due to caudate impairment is discussed in the sense of frontal-subcortical circuits: lateral orbitofrontal and anterior cingulate ones. We emphasise a similarity of behavioural and cognitive disorders in early Huntington's disease and in frontal lobe lesion.     

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.     

Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder

Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive-compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral-metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive-compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive-compulsive symptoms. In particular, the frontal-subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD.     

Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse.

BACKGROUND: Animal studies have shown that early stressors result in lasting changes in structure and function of brain areas involved in memory, including hippocampus and frontal cortex. Patients with childhood abuse-related posttraumatic stress disorder (PTSD) have alterations in both declarative and nondeclarative memory function, and imaging studies in PTSD have demonstrated changes in function during stimulation of trauma-specific memories in hippocampus, medial prefrontal cortex, and cingulate. The purpose of this study was to assess neural correlates of emotionally valenced declarative memory in women with early childhood sexual abuse and PTSD. METHODS: Women with early childhood sexual abuse-related PTSD (n = 10) and women without abuse or PTSD (n = 11) underwent positron emission tomographic (PET) measurement of cerebral blood flow during a control condition and during retrieval of neutral (e.g., "metal-iron") and emotionally valenced (e.g., "rape-mutilate") word pairs. RESULTS: During retrieval of emotionally valenced word pairs, PTSD patients showed greater decreases in blood flow in an extensive area, which included orbitofrontal cortex, anterior cingulate, and medial prefrontal cortex (Brodmann's areas 25, 32, 9), left hippocampus, and fusiform gyrus/inferior temporal gyrus, with increased activation in posterior cingulate, left inferior parietal cortex, left middle frontal gyrus, and visual association and motor cortex. There were no differences in patterns of brain activation during retrieval of neutral word pairs between patients and control subjects. CONCLUSIONS: These findings are consistent with dysfunction of specific brain areas involved in memory and emotion in PTSD. Regions implicated in this study of emotionally valenced declarative memory are similar to those from prior imaging studies in PTSD using trauma-specific stimuli for symptom provocation, adding further supportive evidence for a dysfunctional network of brain areas involved in memory, including hippocampus, medial prefrontal cortex, and cingulate, in PTSD.     

Neuronal linkage of the cerebral cortex and the striatum

The striatum is the major input station of the basal ganglia. It receives a wide variety of inputs from all areas of the cerebral cortex. In particular, there are several parallel loop circuits, such as the motor, oculomotor, dorsolateral prefrontal, lateral orbitofrontal, and anterior cingulate loops, linking the frontal lobe and the basal ganglia. With respect to the motor loop, the motor-related areas, including the primary motor cortex, supplementary motor area, dorsal and ventral premotor cortices, presupplementary motor area, and rostral and caudal cingulate motor areas, send inputs to sectors of the putamen in combination via separate (parallel) and overlapping (convergent) pathways. Such signals return to the cortical areas of origin via the globus pallidus/substantia nigra and then the thalamus. The somatotopical representation is maintained in each structure that constitutes the motor loop. Employing retrograde transsynaptic transport of rabies virus, we have recently investigated the arrangement of multisynaptic pathways linking the basal ganglia to the caudal aspect of the dorsal premotor cortex (the so-called F2). F2r, the rostral sector of F2, has been shown to be involved in motor planning, whereas F2c, the caudal sector of F2, has been shown to be involved in motor execution. We analyzed the origins of multisynaptic inputs to F2r and F2c in the basal ganglia. Our results indicate that the 2 loop circuits connecting the F2r and F2c with the basal ganglia may possess a common convergent window at the input stage, while they have parallel divergent channels at the output stage.     

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

BACKGROUND: Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS: Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS: We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS: While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.     

Some observations on the course and composition of the cingulum bundle in the rhesus monkey

The course and composition of the cingulum bundle was examined by using the autoradiographic tracer technique in the rhesus monkey. The cingulum bundle is observed to consist of three major fiber components originating from thalamus, cingulate gyrus, and cortical association areas. Following isotope injections in the anterior and lateral dorsal thalamic nuclei, labelled fibers form an arch in the white matter behind the cingulate sulcus and occupy the ventral sector of the cingulum bundle. The fibers from the anterior thalamic nucleus coursing in the cingulum bundle extended rostrally to the frontal cortex and caudally to area 23 and the retrosplenial cortex. In contrast, the fibers from lateral dorsal nucleus reached the retrosplenial cortex as well as the parahippocampal gyrus and presubiculum. Efferent fibers from the cingulate gyrus occupy a dorsolateral sector of the cingulum bundle. Those fibers from area 24 of the cingulate gyrus are directed to the premotor and prefrontal regions as well as area 23 and retrosplenial cortex. The fibers from area 23 extend rostrally to the prefrontal cortex and caudoventrally to the presubiculum and parahippocampal gyrus. Finally, an association component originates mainly from prefrontal cortex and posterior parietal region. These fibers occupy a more dorsal and lateral periphery in the cingulate white matter. Cingulum bundle fibers from the prefrontal cortex extend up to the retrosplenial cortex while those from the posterior parietal cortex extend caudally to the parahippocampal gyrus and presubiculum, and rostrally up to the prefrontal cortex.