Anatomic Correlates and Surgical Experience with Goel Orbital Cortical Approach to Caudate Head Tumors.

OBJECTIVE: We analyzed cortical landmarks, trajectory of approach, and various fiber tracts in the vicinity of our earlier described approach through the orbital/basal surface of the frontal lobe to access tumors located in the region of the caudate nucleus. We also present a new lateral orbital trajectory to approach these tumors. METHODS: The orbital surfaces of 3 formalin fixed and frozen cadaveric brain specimens were dissected to decipher the white fibers in the region of the caudate nucleus. Safe trajectories to lesions of the head of the caudate nucleus were identified, and the anatomic landmarks of the approach were evaluated. Three patients with caudate head tumors were operated using this approach. RESULTS: The caudate head lies at an average distance of 34 mm from the tip of the frontal pole, 24 mm from the basal medial orbital surface of the frontal lobe, 35 mm from the basal lateral orbital surface, and 37 mm from the superior surface of the frontal lobe. Two avenues were identified to approach the caudate head: one by making a cortical incision in the lateral orbital gyrus (lateral orbital approach), and the second by making a corticectomy in the medial orbital gyrus (medial orbital approach) in line with the temporal pole. All 3 patients were operated successfully using this approach. CONCLUSIONS: Surgical approach to the caudate head through the orbital surface of the frontal lobe as described by us provides the shortest trajectory and safe surgical route to access tumors of the caudate nucleus.

Glutaminergic signaling in the caudate nucleus is required for behavioral sensitization to methylphenidate.

Methylphenidate (MPD) is a widely prescribed psychostimulant for the treatment of attention deficit hyperactivity disorder, and is growing in use as a recreational drug and academic enhancer. MPD acts on the reward/motive and motor circuits of the CNS to produce its effects on behavior. The caudate nucleus (CN) is known to be a part of these circuits, so a lesion study was designed to elucidate the role of the CN in response to acute and chronic MPD exposure. Five groups of n = 8 rats were used: control, sham CN lesions, non-specific electrolytic CN lesions, dopaminergic-specific (6-OHDA toxin) CN lesion, and glutaminergic-specific (ibotenic acid toxin) CN lesions. On experimental day (ED) 1, all groups received saline injections. On ED 2, surgeries took place, followed by a 5-day recovery period (ED 3-7). Groups then received six daily MPD 2.5 mg/kg injections (ED 9-14), then three days of washout with no injection (ED 15-17), followed by a re-challenge with the previous 2.5 mg/kg MPD dose (ED 18). Locomotive activity was recorded for 60 min after each injection by a computerized animal activity monitor. The electrolytic CN lesion group responded to the MPD acute and chronic exposures similarly to the control and sham groups, showing an increase in locomotive activity, i.e. sensitization. The dopaminergic-specific CN lesion group failed to respond to MPD exposure both acute and chronically. The glutaminergic-specific CN lesion group responded to MPD exposure acutely but failed to manifest chronic effects. This confirms the CN's dopaminergic system is necessary for MPD to manifest its acute and chronic effects on behavior, and demonstrates that the CN's glutaminergic system is necessary for the chronic effects of MPD such as sensitization. Thus, the dopaminergic and glutaminergic components of the CN play a significant role in differentially modulating the acute and chronic effects of MPD respectively.

Quantification of Microsurgical Anatomy in Three-Dimensional Model: Transfrontal Approach for Anterior Portion of the Thalamus.

The thalamus located in the deep site of cerebrum with the risk of internal capsule injury during operation. The purpose of this study was to compare the anatomy for exposure and injury using simulative surgical corridor of 3-dimensional model. The 3-dimensional anatomy model of thalamus in cerebrum was created based on magnetic resonance imaging performed for 15 patients with trigeminal neuralgia. The midpoint of line between anterior edge and top of thalamus was the target exposed. Axis connecting the target with the anterior edge and top of caudate head was used to outline the cylinder, respectively, simulating surgical corridors 1 and 2 of transfrontal approach. Cerebral tissues involved in the corridors were observed, measured, and compared. Incision of cortex was made on the anterior portion of inferior frontal gyrus through corridor 1 and middle frontal gyrus through corridor 2. Both of the 2 corridors passed the caudate nucleus, the anterior limb and genu of internal capsule, ultimately reached the upper anterior portion of thalamus. The volumes of white matter, caudate head, and thalamus in the corridor 1 were more than those in corridor 2. Conversely, the volumes of cortex, internal capsule in corridor 2 were more than those in corridor 1. In conclusion, surgical anatomy-specific volume is helpful to postulate the intraoperative injury of transfrontal approach exposing anterior portion of the thalamus. The detailed information in the quantification of microsurgical anatomy will be used to develop minimally invasive operation.

The neuromorphological caudate-putaminal clustering of neostriate interneurons: Kohonen self-organizing maps and supervised artificial neural networks with multivariate analysis.

AIMS: The objective of this study is to investigate the possibility of the neuromorphotopological clustering of neostriate interneurons (NSIN) and their consequent classification into caudate (CIN) and putaminal neuron type (PIN), according to the nuclear localization of the neurons. It tends to discover whether these two topological neuron types are morphologically different. MATERIAL AND METHODS: The binary images of adult human NSIN are used for the purposes of the analysis. The total of the 46 neuromorphological parameters is used. They can be divided into the following classes: neuron surface/size, shape, compartmental length, dendritic branching, neuromorphological organization and complexity. The clustering is performed by an algorithm which consists of the steps of predictor extraction, multivariate cluster analysis set and cluster identification. RESULTS: Unifactor analysis extracted as significant the following parameters: neurosoma/perikaryon size (AS), the size of a dendritic tree (ADT), the size of a dendritic field area (ADF), the size of an entire neuron field area (ANF), the size of a perineuronal space (APNS), the fractal dimension of a neuron (DN), the index of perikaryon asymmetry (MS), total dendritic length (L), standardized total dendritic length (Lst), standardized dendritic width (DWDTHst), dendritic centrifugal branching order (DCBO), branching polarization index (MDCBO), dendritic partial surface (DSP), the fractal dimension of a skeletonized neuron image (DS), the index of maximal complex density of a dendritic tree (NMAX) and standardized dendritic branching pattern complexity (CDF/ADFst). The cluster analysis set together with Kohonen self-organizing maps and backpropagation feed-forward artificial neural networks confirmed the classification on both unsupervised and supervised manner, respectively. As a final step, the cluster identification is performed by an assignment of each neuron to a particular cluster. CONCLUSION: NSIN can be classified neuromorphologically into CIN and PIN type. Differences are expected since the two nuclei have different functional roles in processing the information involved in volitional movement control.

Subcortical surgical anatomy of the lateral frontal region: human white matter dissection and correlations with functional insights provided by intraoperative direct brain stimulation: laboratory investigation.

OBJECT: Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon's awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome. METHODS: Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition. RESULTS: The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth. CONCLUSIONS: Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

Anatomical connectivity between subcortical structures.

Understanding anatomical connectivity is crucial for improving outcomes of deep brain stimulation surgery. Tractography is a promising method for noninvasively investigating anatomical connectivity, but connections between subcortical regions have not been closely examined by this method. As many connections to subcortical regions converge at the internal capsule (IC), we investigate the connectivity through the IC to three subcortical nuclei (caudate, lentiform nucleus, and thalamus) in six macaques. We show that a statistical correction for a known distance-related artifact in tractography results in large changes in connectivity patterns. Our results suggest that care should be taken in using tractography to assess anatomical connectivity between subcortical structures.

MRI volumetric and 31P MRS metabolic correlates of caudate nucleus in antipsychotic-naïve schizophrenia.

OBJECTIVE: To examine the volumetric and metabolic correlates of caudate nucleus in antipsychotic-naïve schizophrenia patients in comparison with healthy controls. METHOD: Twelve antipsychotic-naïve schizophrenia patients and 13 healthy controls underwent (31)P magnetic resonance spectroscopy of basal ganglia. Magnetic resonance imaging volume of caudate nuclei was measured using scion image software. RESULTS: Patients had significantly smaller caudate volume than healthy controls. Phosphocreatine (PCr)/total phosphorous and PCr/total adenosine tri-phosphate ratios of both caudate nuclei were significantly lower in patients than controls. Significant negative correlation was found between the left caudate volume and left PCr/total phosphorus ratio in the patients. Age at onset of psychosis had i) significant negative correlation with right and left caudate volumes and ii) significant positive correlation with left PCr/total phosphorus ratio. CONCLUSION: The metabolic and volumetric abnormalities of caudate nucleus in antipsychotic-naïve schizophrenia patients support neurodevelopmental etiopathogenesis.

Cognitive- and movement-related potentials recorded in the human basal ganglia.

Sources of potentials evoked by cognitive processing of sensory and motor activities were studied in 9 epilepsy surgery candidates with electrodes implanted in the basal ganglia (BG), mostly in the putamen. Several contacts were also located in the pallidum and the caudate. The recorded potentials were related to a variety of cognitive and motor activities (attentional, decisional, time estimation, sensory processing, motor preparation, and so on). In five different tests, we recorded P3-like potentials evoked by auditory and visual stimuli and sustained potential shifts in the Bereitschaftspotential and Contingent Negative Variation protocols. All of the studied potentials were generated in the BG. They were recorded from all over the putamen. Various potentials on the same lead or nearby contacts were recorded. A functional topography in the BG was not displayed. We presume that the cognitive processes we studied were produced in clusters of neurons that are organized in the basal ganglia differently than the known functional organization, e.g., of motor functions. The basal ganglia, specifically the striatum, may play an integrative role in cognitive information processing, in motor as well as in nonmotor tasks. This role seems to be nonspecific in terms of stimulus modality and in terms of the cognitive context of the task.

Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli.

OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.

Use of magnetic resonance imaging for in vivo measurements of water content in human brain: method and normal values.

OBJECT: The authors present a quantitative in vivo magnetic resonance (MR) imaging method and propose its use for the accurate assessment of brain water in humans. METHODS: With this technique, a pure T1-weighted image of a selected brain slice in a patient is generated, and the image is subsequently converted to a pure water image by means of an equation derived from a tissue relaxation model. The image intensity in the resulting water map directly yields absolute measures of water expressed in grams of water per gram of tissue at a given anatomical location. The method has been validated previously in a series of phantom experiments and in an infusion model of brain edema in cats. In this report, the authors evaluate the method by using samples of tissue harvested from patients who underwent surgery for brain tumor removal and apply the technique to a series of normal volunteers, providing average regional brain water content (f(w)) values for a range of tissues. Application of the method in pathological conditions such as head trauma, tumor, and hydrocephalus allows quantification of regional or global increases in f(w) that result from edema. CONCLUSIONS: It is now possible to obtain accurate brain water measurements with the anatomical resolution of MR imaging. This permits monitoring of the development and resolution of edema in a variety of clinical circumstances, thus enhancing understanding of the underlying pathophysiological processes.

Subgroups of parkinsonian patients differentiated by peptidergic immunostaining of caudate nucleus biopsies.

In this study, Met-enkephalin (Met-enk), substance P (SP) and tyrosine hydroxylase (TH) immunostaining was assessed in caudate nucleus biopsies from 15 Parkinson's disease patients who were treated surgically. According to the combination of changes in Met-enk, SP and TH immunostaining, several subgroups of parkinsonian patients were disclosed. Group I: Patients showing low SP and normal Met-enk immunostaining, and variably reduced TH immunoreactivity. Group II: both SP and Met-enk immunostaining were apparently of normal intensity in these PD patients, but they showed the greatest decrease in TH labeling. Group III: PD patients that showed normal SP, very low Met-enk and variably reduced TH immunostaining. Low Met-enk immunostaining tended to correlate with the severity of the disease as judged by higher Unified Parkinson's disease Rating Scale and gait scores. These results suggest that different neurochemical phenotypes may exist among Parkinson's disease patients. Peptidergic deficits should be taken into account for therapeutic intervention.

MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content.

PURPOSE: To determine the transverse relaxation rates R2 and R2' from several gray matter regions and from frontal cortical white matter in healthy human brains in vivo and to determine the relationship between relaxation rates and iron concentration [Fe]. MATERIALS AND METHODS: Six healthy adults aged 19-42 years underwent thin-section gradient-echo sampling of free induction decay and echo magnetic resonance (MR) imaging at 3.0 T. Imaging covered the mesencephalon and basal ganglia. RESULTS: Relaxation rates (mean +/- SD) were highest in globus pallidus (R2 = 25.8 seconds-1 +/- 1.1, R2' = 12.0 seconds-1 +/- 2.1) and lowest in prefrontal cortex (R2 = 14.4 seconds-1 +/- 1.8, R2' = 3.4 seconds-1 +/- 1.1). Frontal white matter measurements were as follows: R2 = 18.0 seconds-1 +/- 1.2 and R2' = 3.9 seconds-1 +/- 1.2. For gray matter, both R2 and R2' showed a strong correlation (r = 0.92, P < .001 and r = 0.90, P < .001, respectively) with [Fe]. Although the slopes of the regression lines for R2' versus [Fe] and for R2 versus [Fe] were similar, the iron-independent component of R2' (2.2 seconds-1 +/- 0.6), the value when [Fe] = 0, was much less than that of R2 (12.7 seconds-1 +/- 0.7). CONCLUSION: The small iron-independent component R2', as compared with that of R2, is consistent with the hypothesis that R2' has higher iron-related specificity.

MR evaluation of age-related increase of brain iron in young adult and older normal males.

The purposes of this study were to extend the investigation of age-related increases in brain iron to a younger age group, replicate previously published results, and further evaluate the validity of a novel noninvasive magnetic resonance (MR) method for measuring tissue iron (ferritin) levels with specificity. The method consists of measuring the dependence of tissue transverse relaxation rates (R2) on the field strength of MR instruments. Two MR instruments operating at 1.5 and 0.5 T were used to measure the field-dependent R2 increase (FDRI) in the frontal white matter, caudate, putamen, and globus pallidus. A group of 13 normal adult males (ages 21-77), with seven subjects below and six above age 35, was examined. As expected from postmortem and prior FDRI data, robust and significant age-related increases in FDRI were observed in the caudate, putamen, and globus pallidus, with the globus pallidus FDRI increasing sharply in the second decade and reaching a plateau after age 30. In addition, we replicated previous reports showing very high correlations between FDRI and published brain iron levels for the four regions examined. The data replicate and extend previous FDRI observations on brain aging and are consistent with postmortem data on age-related increases in brain iron. These results are relevant to the investigation of age-related neurodegenerative diseases in which iron may catalyze toxic free radical reactions.

Involvement of mechanisms dependent on NMDA receptors, nitric oxide and protein kinase A in the hippocampus but not in the caudate nucleus in memory.

The effects of the NMDA receptor antagonist AP5, the nitric oxide synthase (NO) inhibitor NO-arg or the protein kinase A (PKA) inhibitor KT5720 on memory were evaluated. Rats bilaterally implanted in the CA1 region of the dorsal hippocampus were trained and tested in a step-down inhibitory avoidance task, and rats unilaterally implanted in the left posteroventral region of the caudate nucleus were trained and tested in a cued water maze task. Previous findings from this and other laboratories had found that lesions or pharmacological treatments of these sites significantly altered memory of these two tasks. Immediately after training, animals received intrahippocampal or intracaudate 0.5 microliter microinfusions of saline, AP5, NO-arg or KT5720. All three drugs impaired retention of inhibitory avoidance, but did not affect retention of the cued water maze. The findings suggest that NMDA receptor-, NO- and PKA-mediated processes in the dorsal hippocampus, but not in the caudate nucleus, are involved in memory.

Effects of D2 dopamine receptor antagonists on Fos protein expression in the striatal complex and entorhinal cortex of the nonhuman primate.

Recent studies have reported that acute administration of dopamine D2 receptor antagonists increases expression of the immediate early gene c-fos in the rat striatal complex. There have been no corresponding studies of the effects of D2 antagonists in primate species. Since all clinically effective antipsychotic drugs share D2 receptor antagonism, it is important to define the extent to which these drugs may alter expression of c-fos or its protein product, Fos, in primates. We therefore examined the effects of administration of two D2 receptor antagonists, haloperidol and metoclopramide, on Fos expression in the striatum and temporal cortices of the vervet monkey. Metoclopramide does not appear to possess significant antipsychotic efficacy but potently produces extra-pyramidal side effects, while haloperidol is an effective antipsychotic drug that produces extrapyramidal side effects. Both drugs increased the number of Fos-like immunoreactive (Fos-li) neurons in the caudate nucleus and putamen; the numbers of Fos-li neurons in these regions were increased in both the patch and matrix compartments. Haloperidol but not metoclopramide increased the number of Fos-li neurons in the nucleus accumbens shell. Similarly, haloperidol but not metoclopramide increased the number of Fos-li neurons in the entorhinal cortex. Neither drug altered Fos expression in the inferior temporal cortex. These data suggest that the dorsolateral caudate nucleus and putamen may be sites at which D2 receptor antagonists elicit extrapyramidal side effects, and the nucleus accumbens shell and entorhinal cortex may be loci at which the therapeutic actions of antipsychotic drugs are manifested.

Ultrasound-guided brain biopsy in dogs.

Ultrasound-guided brain biopsy of the cingulate gyrus and the head of the caudate nucleus was performed in clinically normal dogs. Dogs survived the surgery, and neurologic deficits were not detected in the 14-day postoperative period. Magnetic resonance imaging detected changes in the brain associated with biopsy in 9 dogs (90%) immediately after surgery and in 6 dogs (60%) 14 days after surgery. Fourteen days after surgery, sonography of the brain, performed through the skin overlying the burr hole, detected changes associated with biopsy in 9 dogs (90%). Histopathologic changes evident in the brain 14 days after surgery consisted of focal malacia and hemorrhage with associated subacute encephalomeningitis. Postmortem examination indicated that the biopsy specimen was accurately obtained from the desired site in 9 dogs (90%). Tissue specimens suitable for histologic examination were obtained from 10 dogs (100%). Accuracy and low morbidity of ultrasound-guided biopsy indicate that this may be a useful technique for diagnosis of focal brain disease in dogs.

Adenosinergic modulation of the EEG and locomotor effects of the A2 agonist, CGS 21680.

The present study in rats was designed to identify the respective roles of A1 and A2 adenosine receptor activation in the anticonvulsant and behavioral actions of adenosine. Intracaudate injections of the highly selective A2 agonist, CGS 21680, did not affect caudate seizures. However, seizure threshold was increased in the presence of CGS 21680 after blockade of the A1 receptor with CPX, or following activation of the A1 receptor with R-PIA or NECA. Additionally, CGS 21680 led to a dose-related inhibition of locomotor activity when injected into the caudate. These results implicate the involvement of the A2 adenosine receptor in the locomotor depressant actions of adenosine and also suggest possible A2 anticonvulsant effects may depend upon the activation of the A1 receptor.

5'-nucleotidase: a new marker for striosomal organization in the rat caudoputamen.

The distribution of the adenosine-producing ectoenzyme 5'-nucleotidase was studied by means of a histochemical lead technique in the caudoputamen of normal adult rats and of rats in which injections either of 6-hydroxydopamine in the medial forebrain bundle or of ibotenic acid in the caudoputamen had been made 1-3 weeks previously. The patterns of striatal 5'-nucleotidase activity in these animals were compared in serial sections to the patterns of calbindin-D28k immunoreactivity and of 3H-naloxone ligand binding, which respectively mark the known matrix and striosome (patch) compartments of the caudoputamen. In the normal rats, 5'-nucleotidase activity was differentially concentrated in striosomes, where it produced a dense staining of the neuropil. The enzymatic staining followed a striosomal distribution in all but the caudal caudoputamen. Within the striatal matrix, 5'-nucleotidase staining also observed a lateromedial density gradient. Depletion of the dopamine-containing nigrostriatal innervation of the caudoputamen with 6-hydroxydopamine did not alter the striosomal selectivity of 5'-nucleotidase activity. Destruction of intrastriatal neurons by ibotenic acid led to a strongly 5'-nucleotidase-positive gliosis within the resulting necrotic region. Elsewhere in the caudoputamen, the enzyme's striosomal distribution was not detectably altered. We conclude that 5'-nucleotidase histochemistry provides an advantageous tool for detecting the striosomal architecture of the rat's caudoputamen. Moreover, 5'-nucleotidase is prominently associated with glial membranes in the central nervous system, so that the concentration of this enzyme in striosomes could mark these as sites of selective glial populations within striatum. These properties and actions of 5'-nucleotidase in purinergic neurotransmission and in neuroadhesion may contribute to the specialized functions of striosomes and matrix.

Quantitative magnetic resonance imaging in heroin- and cocaine-dependent men: a preliminary study.

Quantitative magnetic resonance imaging (MRI) of the brain was performed in nine drug-dependent men with a primary diagnosis of opioid and/or cocaine dependence, and 10 age-matched, non-drug-dependent controls. Individuals were screened for the presence of gross cerebral abnormalities before T1 and T2 analyses. Regional T1 and T2 times were calculated on a single 5-mm thick axial slice positioned just below the caudal margin of the lateral ventricles, passing through the caudate and putamen. A voxel of interest (VOI) cursor was placed bilaterally within the putamen, caudate, frontal gray matter, frontal white matter, or posterior white matter. T1 and T2 values were determined for each VOI using an iterative chi 2 minimization program. T1 and T2 relaxation times did not differ significantly between the subject groups in any brain region studied. These results suggest that T1 and T2 relaxation times may not identify microstructural central nervous system changes resulting from chronic opiate and cocaine abuse.

Neuropeptide content and connectivity of the rat claustrum.

The rat claustrum has a homogeneous distribution of the neuropeptides somatostatin (SOM), cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP) along its rostrocaudal axis. In general, neuropeptide levels are comparable to those of overlying pyriform cortex. Visualization of mRNA encoding SOM, CCK and VIP in cell bodies of the claustrum by in situ hybridization histochemistry demonstrates that all 3 neuropeptides are contained in intrinsic claustral neurons. Mid-coronal section of the claustrum itself, or interruption of potential rostral, caudal or medial connections between the claustrum and the rest of the brain did not significantly alter levels of VIP, SOM or CCK in claustrum, cerebral cortex, or basal ganglia. Isolation of the claustrum from the cerebral cortex immediately dorsal to it along its rostrocaudal aspect caused no change in peptide levels in claustrum indicating that VIP, SOM and CCK projections to claustrum do not arrive from dorsal cortical areas. Transection of the external capsule above the claustrum caused a 50-100% elevation of all 3 peptides on the contralateral side of the lesion, suggesting that VIP, SOM and CCK synthesis and/or release within the claustrum may be regulated by projections from the contralateral side. VIP, SOM and CCK are candidates for neurotransmitters contained in neurons whose cell bodies are within the claustrum and possibly also immediately overlying lateral neocortex, and have their terminals mainly within the claustrum itself.