Medial Cortical Areas Research Articles

Prognostic associations of cortical gyrification in minimally medicated schizophrenia in an early intervention setting

The aberration in cortical gyrification seen in schizophrenia likely originates in the earliest phase of life, as gyrification begins in utero and reaches its peak in infancy. However, emerging observations have indicated a later reduction in gyrification, especially in early adulthood, may also occur in schizophrenia. At present, it is unclear whether the baseline and later gyrification reduction has any prognostic importance in schizophrenia. We address this question in a longitudinal design in patients minimally medicated at inception. About 108 minimally medicated (duration of medication = <14 days of antipsychotics) patients and 106 healthy controls underwent structural magnetic resonance imaging, with 34 patients being selectively re-scanned when clinically stable following antipsychotic treatment. The cortical surface from each structural image was reconstructed, and the local gyrification index and cortical thickness were computed for each vertex on the surface. We found minimally medicated schizophrenia patients during the first episode had a relatively higher gyrification in bilateral supramarginal, left superior temporal, and right posterior cingulate and paracentral regions. However, poor prognostic features were more likely in patients with lower baseline gyrification. Longitudinal reductions in left superior parietal and right precentral gyrification were associated with lower improvements in both positive and negative symptoms over time. The spatial pattern of longitudinal changes in gyrification was distinct from the changes in cortical thickness. These results indicated that schizophrenia is characterized by a relative hypergyrification in parieto-temporal and medial cortical areas at a group level at first presentation, but poor outcomes relate to lower-gyrification elsewhere both at the onset and during the early course. The early post-onset reduction of gyrification is rather limited in space and magnitude, but occurs unrelated to the progressive thinning, representing a distinct, prognostically important structural trajectory.

A Direct Comparison of Afferents to the Rat Anterior Thalamic Nuclei and Nucleus Reuniens: Overlapping But Different.

Both nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective contributions to learning and memory. To better appreciate their comparative roles, pairs of different retrograde tracers were placed in these two thalamic sites in adult rats. Both thalamic sites receive modest cortical inputs from layer V that contrasted with much denser projections from layer VI. Despite frequent overlap in layer VI, ventral prefrontal and anterior cingulate inputs to nucleus reuniens were concentrated in the deepest sublayer (VIb). Meanwhile, inputs to the anterior thalamic nuclei originated more evenly from both sublayers VIa and VIb, with the result that they were often located more superficially than the projections to nucleus reuniens. Again, while the many hippocampal (subiculum) neurons projecting to nucleus reuniens and the anterior thalamic nuclei were partially intermingled within the deep cellular parts of the subiculum, cells projecting to nucleus reuniens consistently tended to lie even deeper (i.e., immediately adjacent to the alveus). Variable numbers of double-labeled cells were present in those cortical and subicular portions where the two cell populations intermingled, though they remained in a minority. Our data also show how projections to these two thalamic sites are organized in opposing dorsal/ventral and rostral/caudal gradients across both the cortex and hippocampal formation. While the anterior thalamic nuclei are preferentially innervated by dorsal cortical sites, more ventral frontal sites preferentially reach nucleus reuniens. These anatomic differences may underpin the complementary cognitive functions of these two thalamic areas.

The Behavioral and ERP Responses to Self- and Other- Referenced Adjectives.

The aim was to investigate behavioral reactions and event-related potential (ERP) responses in healthy participants under conditions of personalized attribution of emotional appraisal vocabulary to one-self or to other people. One hundred and fifty emotionally neutral, positive and negative words describing people’s traits were used. Subjects were asked to attribute each word to four types of people: one-self, loved, unpleasant and neutral person. The reaction time during adjectives attribution to one-self and a loved person was shorter than during adjectives attribution to neutral and unpleasant people. Self-related adjectives induced higher amplitudes of the N400 ERP peak in the medial cortical areas in comparison with adjectives related to other people. The amplitude of P300 and P600 depended on the emotional valence of assessments, but not on the personalized attribution. The interaction between the attribution effect and the effect of emotional valence of assessments was observed for the N400 peak in the left temporal area. The maximal amplitude of N400 was revealed under self-attributing of emotionally positive adjectives. Our results supported the hypothesis that the emotional valence of assessments and the processing of information about one-self or others were related to the brain processes that differ from each other in a cortical localization or time dynamics.

Ontogenetic changes of tissue compartmentalization and bone type distribution in the humerus of Soay sheep.

We studied ontogenetic changes of histomorphological features and bone type distribution in the humeral midshaft region of Soay sheep from three postnatal age classes (13, 25, and 33months). Our study demonstrated a marked change of bone type distribution in the humeri with age. In the cortical midshaft region of 13-month-old individuals, periosteal fibrolamellar bone was the dominating bone type. This indicates a rapid bone growth during the first year of life, which was only interrupted by a seasonal growth arrest in the animals' first winter. In individuals from the two older age classes, periosteal lamellar-zonal bone and intermediate fibrolamellar bone had been formed at the periosteal surface, and endosteal lamellar-zonal bone at the endosteal surface. These bone types are indicative of a reduced bone growth rate. A marked reduction in radial growth was already recorded in the 25-month-old individuals. Distribution and extent of secondary bone showed a marked bilateral symmetry in the humeri of individual sheep. The presence of secondary bone was largely restricted to the anterior (cranial) and the medial cortical areas. This characteristic distribution of remodeling activity within the humeral cortex of sheep is consistent with the view that remodeling activity is largely caused by compressive stress. Our study further demonstrated the presence of a considerable cortical drift in the sheep humeri over the study period, with endosteal resorption occurring predominantly in the posterior (caudal) quadrant and formation of a prominent endosteal lamellar pocket in the anterior (cranial) and medial cortical quadrants.

Transcutaneous Vagus Nerve Stimulation Affects Implicit Spiritual Self-Representations

Recently, the empirical interest in religiousness and spirituality has grown, showing the association between the activity of a complex network of subcortical and fronto-parietal areas and explicit and implicit religious/spiritual representations. Importantly, while the causal link between parietal stimulation and implicit religiousness/spirituality has been demonstrated, the role of subcortical and medial cortical areas has not been directly investigated. Here, we assessed how implicit and explicit religious or spiritual representations are modulated by transcutaneous Vagus Nerve Stimulation (tVNS), a novel non-invasive method to stimulate subcortical and medial cortical structures. Implicit and explicit representations were tested with Religious, Spiritual and Self-esteem (as control) Implicit Association Tests and questionnaires. Active-tVNS, compared to sham-tVNS, affected implicit spiritual, but not religious or control self-representations, reducing the strength of the automatic association between the self and the spiritual dimension. Explicit self-representations were left unchanged. Findings shed new light on the neurobiological mechanisms of implicit spirituality.

Hand Motor Recovery Following Extensive Frontoparietal Cortical Injury Is Accompanied by Upregulated Corticoreticular Projections in Monkey.

We tested the hypothesis that arm/hand motor recovery after injury of the lateral sensorimotor cortex is associated with upregulation of the corticoreticular projection (CRP) from the supplementary motor cortex (M2) to the gigantocellular reticular nucleus of the medulla (Gi). Three groups of rhesus monkeys of both genders were studied: five controls, four cases with lesions of the arm/hand area of the primary motor cortex (M1) and the lateral premotor cortex (LPMC; F2 lesion group), and five cases with lesions of the arm/hand area of M1, LPMC, S1, and anterior parietal cortex (F2P2 lesion group). CRP strength was assessed using high-resolution anterograde tracers injected into the arm/hand area of M2 and stereology to estimate of the number of synaptic boutons in the Gi. M2 projected bilaterally to the Gi, primarily targeting the medial Gi subsector and, to a lesser extent, lateral, dorsal, and ventral subsectors. Total CRP bouton numbers were similar in controls and F2 lesion cases but F2P2 lesion cases had twice as many boutons as the other two groups (p = 0.0002). Recovery of reaching and fine hand/digit function was strongly correlated with estimated numbers of CRP boutons in the F2P2 lesion cases. Because we previously showed that F2P2 lesion cases experience decreased strength of the M2 corticospinal projection (CSP), whereas F2 lesion monkeys experienced increased strength of the M2 CSP, these results suggest one mechanism underlying arm/hand motor recovery after F2P2 injury is upregulation of the M2 CRP. This M2-CRP response may influence an important reticulospinal tract contribution to upper-limb motor recovery following frontoparietal injury.SIGNIFICANCE STATEMENT We previously showed that after brain injury affecting the lateral motor cortex controlling arm/hand motor function, recovery is variable and closely associated with increased strength of corticospinal projection (CSP) from an uninjured medial cortical motor area. Hand motor recovery also varies after brain injury affecting the lateral sensorimotor cortex, but medial motor cortex CSP strength decreases and cannot account for recovery. Here we observed that motor recovery following sensorimotor cortex injury is closely associated with increased strength of the descending projection from an uninjured medial cortical motor area to a brainstem reticular nucleus involved in control of arm/hand function, suggesting an enhanced corticoreticular projection may compensate for injury to the sensorimotor cortex to enable recovery of arm/hand motor function.

Neurophysiology of spontaneous facial expressions: I. Motor control of the upper and lower face is behaviorally independent in adults

Facial expressions are described traditionally as monolithic entities. However, humans have the capacity to produce facial blends, in which the upper and lower face simultaneously display different emotional expressions. This, in turn, has led to the Component Theory of facial expressions. Recent neuroanatomical studies in monkeys have demonstrated that there are separate cortical motor areas for controlling the upper and lower face that, presumably, also occur in humans. The lower face is represented on the posterior ventrolateral surface of the frontal lobes in the primary motor and premotor cortices and the upper face is represented on the medial surface of the posterior frontal lobes in the supplementary motor and anterior cingulate cortices. Our laboratory has been engaged in a series of studies exploring the perception and production of facial blends. Using high-speed videography, we began measuring the temporal aspects of facial expressions to develop a more complete understanding of the neurophysiology underlying facial expressions and facial blends. The goal of the research presented here was to determine if spontaneous facial expressions in adults are predominantly monolithic or exhibit independent motor control of the upper and lower face. We found that spontaneous facial expressions are very complex and that the motor control of the upper and lower face is overwhelmingly independent, thus robustly supporting the Component Theory of facial expressions. Seemingly monolithic expressions, be they full facial or facial blends, are most likely the result of a timing coincident rather than a synchronous coordination between the ventrolateral and medial cortical motor areas responsible for controlling the lower and upper face, respectively. In addition, we found evidence that the right and left face may also exhibit independent motor control, thus supporting the concept that spontaneous facial expressions are organized predominantly across the horizontal facial axis and secondarily across the vertical axis.

Dopamine and glutamate release in the anterior default system during rest: A monkey microdialysis study

Human neuroimaging studies have demonstrated the presence of a default system in the brain, which shows a default mode of brain activity, i.e., greater activity during rest than during an attention-demanding cognitive task. Our previous study on monkeys has revealed a default mode of brain activity in medial cortical areas. We have observed an increase in dopamine (DA) release during a working memory (WM) task compared with that during rest in the monkey lateral prefrontal cortex (LPFC). However, no previous study has examined DA release related to the default mode of brain activity. We used a microdialysis technique to investigate changes in DA release in the medial prefrontal cortex (MPFC), which constitutes the anterior default system, during the WM task and rest. Because DA and glutamate (Glu) release in the LPFC is interrelated, we also examined Glu release in the MPFC. We observed a significant increase in DA release, but no significant change in Glu release during rest compared with that during the WM task. We also observed an inhibitory relationship between the two transmitters in the MPFC. Considering that human default brain activity is related to internal thought processes and increased DA release in the LPFC plays an important role in executive control, increase in DA release during rest in the monkey anterior default system may be related to some form of internal thought process.

The spatial synchronization and power of the alpha and theta rhythm after Go/NoGo signals

Conditioning Go/NoGo signals, which determine the triggering stimulus conditional value, were presented to healthy adult subjects (n = 35) in the pause between the target (facial expression) and triggering stimuli. The response of the low-frequency α rhythm to conditioning stimuli was more pronounced in the left hemisphere. The coherence of cortical low-frequency alpha potentials increased 5–7 s after presenting both positive and negative conditioning (Go/NoGo) stimuli (i.e., immediately before the triggering stimulus). These data confirm the assumption that the development of differentiation requires not less functional activity than the development of a positive conditional response. The modulation of cortical activity after presenting Go/NoGo stimuli is mediated primarily by the thalamocortical system of selective attention. The coherence of θ rhythm after the presentation of positive conditioning stimuli was more pronounced in the medial cortical areas, which was apparently determined by the emotional memory function.

Chronic administration of haloperidol and clozapine induces differential effects on the expression of Arc and c-Fos in rat brain.

The modulation of genes implicated in synaptic plasticity following administration of antipsychotic drugs has been instrumental in understanding their possible mode of action. Arc (Arg 3.1) is one such gene closely associated with changes in synaptic plasticity. In this study we have investigated the changes in expression of Arc protein following acute and chronic administration of a typical antipsychotic (haloperidol) and an atypical antipsychotic (clozapine) by means of immunohistochemistry compared to the prototypic gene marker c-Fos. In dorsal striatum haloperidol (1 mg/kg) significantly increased Arc expression following both acute and chronic (21 day) administration with evidence of modulation in induction after repeated dosing. No significant changes were observed following either acute or chronic administration of clozapine (20 mg/kg). In the nucleus accumbens shell both clozapine and haloperidol induced Arc expression following acute administration, again with evidence of modulation after chronic dosing. The pattern of induction of Arc expression following haloperidol and clozapine in both dorsal and ventral striatum was similar to that for c-Fos. In medial prefrontal and cingulate cortex, Arc expression was significantly decreased by clozapine but not haloperidol without any indication of modulation following chronic dosing, whereas no significant changes in c-Fos expression were observed with either drug. Since synaptic modulation mediated by Arc is associated with down-regulation of the AMPA glutamate receptor, this study suggests a mechanism whereby enhanced glutamate receptor efficacy in medial cortical areas may be a component of antipsychotic drug action.

Structural Abnormalities in Schizophrenia: Further Evidence on the Key Role of the Anterior Cingulate Cortex

Objective: The present study examined whole-brain structural abnormalities in schizophrenia, with a special focus on the anterior and posterior cingulate cortex (ACC, PCC) as this is an understudied issue in schizophrenia. Method: Whole-brain voxel-based morphometry analyses of gray matter (GM) and white matter (WM) were performed to detect volumetric differences between 14 patients with schizophrenia and 14 healthy controls matched for age, sex, educational level and parents' educational level. We examined within-group GM and WM correlations and completed the analysis with measurements of sulci in medial cortical areas. Results: Compared with the healthy controls, the schizophrenic patients showed significant decreases in GM volumes in the ACC and PCC, and in neighboring WM regions such as the corpus callosum and the fimbriae of the fornix. Moreover, the patient group also displayed a negative correlation between volumes of GM and WM in the ACC. Finally, the patients showed significantly reduced volumes in the right cingulate sulci and left inferior frontal sulci. Conclusion: Our results replicate typical brain-structural abnormalities with new findings in the medial prefrontal cortex, suggested to be a key region in this disorder.

Combat veterans with PTSD after mild TBI exhibit greater ERPs from posterior–medial cortical areas while appraising facial features

Posttraumatic stress disorder (PTSD) worsens prognosis following mild traumatic brain injury (mTBI). Combat personnel with histories of mTBI exhibit abnormal activation of distributed brain networks—including emotion processing and default mode networks. How developing PTSD further affects these abnormalities has not been directly examined. We recorded electroencephalography in combat veterans with histories of mTBI, but without active PTSD (mTBI only, n=16) and combat veterans who developed PTSD after mTBI (mTBI+PTSD, n=16)—during the Reading the Mind in the Eyes Test (RMET), a validated test of empathy requiring emotional appraisal of facial features. Task-related event related potentials (ERPs) were identified, decomposed using independent component analysis (ICA) and localized anatomically using dipole modeling. We observed larger emotional face processing ERPs in veterans with mTBI+PTSD, including greater N300 negativity. Furthermore, greater N300 negativity correlated with greater PTSD severity, especially avoidance/numbing and hyperarousal symptom clusters. This correlation was dependent on contributions from the precuneus and posterior cingulate cortex (PCC). Our results support a model where, in combat veterans with histories of mTBI, larger ERPs from over-active posterior–medial cortical areas may be specific to PTSD, and is likely related to negative self-referential activity.

Neural correlates of auditory temporal predictions during sensorimotor synchronization

Musical ensemble performance requires temporally precise interpersonal action coordination. To play in synchrony, ensemble musicians presumably rely on anticipatory mechanisms that enable them to predict the timing of sounds produced by co-performers. Previous studies have shown that individuals differ in their ability to predict upcoming tempo changes in paced finger-tapping tasks (indexed by cross-correlations between tap timing and pacing events) and that the degree of such prediction influences the accuracy of sensorimotor synchronization (SMS) and interpersonal coordination in dyadic tapping tasks. The current functional magnetic resonance imaging study investigated the neural correlates of auditory temporal predictions during SMS in a within-subject design. Hemodynamic responses were recorded from 18 musicians while they tapped in synchrony with auditory sequences containing gradual tempo changes under conditions of varying cognitive load (achieved by a simultaneous visual n-back working-memory task comprising three levels of difficulty: observation only, 1-back, and 2-back object comparisons). Prediction ability during SMS decreased with increasing cognitive load. Results of a parametric analysis revealed that the generation of auditory temporal predictions during SMS recruits (1) a distributed network of cortico-cerebellar motor-related brain areas (left dorsal premotor and motor cortex, right lateral cerebellum, SMA proper and bilateral inferior parietal cortex) and (2) medial cortical areas (medial prefrontal cortex, posterior cingulate cortex). While the first network is presumably involved in basic sensory prediction, sensorimotor integration, motor timing, and temporal adaptation, activation in the second set of areas may be related to higher-level social-cognitive processes elicited during action coordination with auditory signals that resemble music performed by human agents.

Integrity of medial temporal structures may predict better improvement of spatial neglect with prism adaptation treatment

Prism adaptation treatment (PAT) is a promising rehabilitative method for functional recovery in persons with spatial neglect. Previous research suggests that PAT improves motor-intentional "aiming" deficits that frequently occur with frontal lesions. To test whether presence of frontal lesions predicted better improvement of spatial neglect after PAT, the current study evaluated neglect-specific improvement in functional activities (assessment with the Catherine Bergego Scale) over time in 21 right-brain-damaged stroke survivors with left-sided spatial neglect. The results demonstrated that neglect patients' functional activities improved after two weeks of PAT and continued improving for four weeks. Such functional improvement did not occur equally in all of the participants: Neglect patients with lesions involving the frontal cortex (n = 13) experienced significantly better functional improvement than did those without frontal lesions (n = 8). More importantly, voxel-based lesion-behavior mapping (VLBM) revealed that in comparison to the group of patients without frontal lesions, the frontal-lesioned neglect patients had intact regions in the medial temporal areas, the superior temporal areas, and the inferior longitudinal fasciculus. The medial cortical and subcortical areas in the temporal lobe were especially distinguished in the "frontal lesion" group. The findings suggest that the integrity of medial temporal structures may play an important role in supporting functional improvement after PAT.

Synchrony of Two Brain Regions Predicts the Blood Oxygen Level Dependent Activity of a Third

Spontaneously emerging coherent fluctuations have been long observed in electrophysiological and functional magnetic resonance imaging studies. These dynamics have been identified in multiple brain areas in the 1-100 and < 0.1 Hz frequency ranges spanning neurophysiological oscillations and blood oxygen level dependent (BOLD) signals, respectively. In this article, we demonstrate that transient neural synchronization between two sites may lead to the emergence of ultra-slow frequency fluctuations in the BOLD signal at another (third) site. Starting with a network model comprised of three neural oscillators, we illustrate the critical role of time delay and coupling strength in generating these slow coherent fluctuations as a function of intermittently occurring neural coherence. When extending the network toward biologically realistic primate connectivity, we find that the BOLD activation patterns arise from neurophysiological coherence, especially among medial cortical areas. This finding demonstrates a network-level mechanism whereby the BOLD activity at a given region is critically influenced by the neuroelectric synchronization patterns of other regions in the network.

Brain activities tell us what animals have in mind

Recent human neuroimaging studies indicate that by using fMRI we can “see” what people are thinking. In animals, we can more accurately see what the animal has in mind by using invasive methods that cannot be used in human subjects. Here I introduce experimental studies where single neuronal activities were examined in the monkey prefrontal cortex in relation to working memory and reward expectancy. We found that by monitoring the neuronal activity while the animal is waiting for the next event, we can see what the monkey is retaining or expecting in mind. Human neuroimaging studies have well documented “default mode of brain activity”, which is higher activity during the resting state than during cognitively demanding task, and is concerned with internal thought processes, in the medial prefrontal and medial parietal areas. In our PET study, we also found higher activity during rest in these medial cortical areas of the monkey. The result suggests that there are primitive-level internal thought processes in the monkey.

Correlated structural and functional brain abnormalities in the default mode network in schizophrenia patients

Background There is increasing evidence of default mode network (DMN) dysfunction in schizophrenia. It has also been suggested that brain structural changes are maximal in a medial frontal area which overlaps with the anterior midline node of this network. Methods Brain deactivations were examined in 14 schizophrenic patients and 14 controls during performance of two tasks requiring identification or labelling of facial emotions. Grey matter and white matter volumes were compared using voxel-based morphometry. Results Relative to the controls, the schizophrenic patients showed failure to deactivate in the anterior and posterior midline nodes of the default mode network, as well as other areas considered to be part of the network. Grey matter volume reductions in the patients were found in medial cortical regions which overlapped with the same parts of the network. The functional and structural changes showed significant correlations in a number of medial cortical areas. Conclusions Failure of deactivation in the default mode network is seen in schizophrenic patients when they perform facial emotion tasks. This failure is more extensive than that seen during performance of working memory tasks. The study also supports recent findings of brain structural changes in schizophrenia in the territory of the default mode network.

Default Mode of Brain Activity Demonstrated by Positron Emission Tomography Imaging in Awake Monkeys: Higher Rest-Related than Working Memory-Related Activity in Medial Cortical Areas

Human neuroimaging studies have demonstrated the presence of a "default system" in the brain, which shows a "default mode of brain activity," i.e., greater activity during the resting state than during an attention-demanding cognitive task. The default system mainly involves the medial prefrontal and medial parietal areas, including the anterior and posterior cingulate cortex. It has been proposed that this default activity is concerned with internal thought processes. Recently, it has been indicated that chimpanzees show high metabolic levels in these medial brain areas during rest. Correlated low-frequency spontaneous activity as measured by functional magnetic resonance imaging was observed between the medial parietal and medial prefrontal areas in the anesthetized monkey. However, there have been few attempts to demonstrate a default system that shows task-induced deactivation in nonhuman primates. We conducted a positron emission tomography study with [(15)O]H(2)O to demonstrate a default mode of brain activity in the awake monkey sitting on a primate chair. Macaque monkeys showed higher level of regional blood flow in these medial brain areas as well as lateral and orbital prefrontal areas during rest compared with that under a working memory task, suggesting the existence of internal thought processes in the monkey. However, during rest in the monkey, the highest level of blood flow relative to that in other brain regions was observed not in the default system but in the dorsal striatum, suggesting that regions with the highest cerebral blood flow during rest may differ depending on the resting condition and/or species.

Topographical Organization of the Pyramidal Fiber System - Diffusion Tensor MRI of the Human and Rhesus Monkey Brain

The fibers of the pyramidal tract (PT) that connect the precentral and postcentral gyrus with the spinal cord are organized in a topological manner. However, their exact arrangement and orientation in the internal capsule is still a mat- ter of debate. Here, we applied magnetic resonance diffusion tensor imaging and tract tracing techniques to determine and compare the pyramidal fibers from the primary motor and somatosensory system in humans and rhesus monkeys in vivo. The results demonstrate that the pyramidal systems of the human and monkey brain differ in their orientation at the level of the internal capsule, whereas track orientations in the gyrus and brainstem appear similar. In the monkey internal cap- sule the somatotopic arrangement of PT fibers from the upper and lower extremities form an angle with the left-right axis of 146° ± 23° (n=4). Thus, fibers from lateral areas of the gyrus are located more anterior-medial to fibers from medial cortical areas. In contrast, in humans the angle is only 50° ± 16° (n=9) yielding a more anterior-lateral orientation of PT fibers along the short axis of the internal capsule. These species dependencies may possibly be due to structural con- straints of the smaller and differently shaped monkey brain.

Cerebral morphology and dopamine D 2/D 3 receptor distribution in humans: A combined [ 18F]fallypride and voxel-based morphometry study

The relationship between cerebral morphology and the expression of dopamine receptors has not been extensively studied in humans. Elucidation of such relationships may have important methodological implications for clinical studies of dopamine receptor ligand binding differences between control and patient groups. The association between cerebral morphology and dopamine receptor distribution was examined in 45 healthy subjects who completed T1-weighted structural MRI and PET scanning with the D 2/D 3 ligand [ 18F]fallypride. Optimized voxel-based morphometry was used to create grey matter volume and density images. Grey matter volume and density images were correlated with binding potential (BP ND) images on a voxel-by-voxel basis using the Biological Parametric Mapping toolbox. Associations between cerebral morphology and BP ND were also examined for selected regions-of-interest (ROIs) after spatial normalization. Voxel-wise analyses indicated that grey matter volume and density positively correlated with BP ND throughout the midbrain, including the substantia nigra. Positive correlations were observed in medial cortical areas, including anterior cingulate and medial prefrontal cortex, and circumscribed regions of the temporal, frontal, and parietal lobes. ROI analyses revealed significant positive correlations between BP ND and cerebral morphology in the caudate, thalamus, and amygdala. Few negative correlations between morphology and BP ND were observed. Overall, grey matter density appeared more strongly correlated with BP ND than grey matter volume. Cerebral morphology, particularly grey matter density, correlates with [ 18F]fallypride BP ND in a regionally specific manner. Clinical studies comparing dopamine receptor availability between clinical and control groups may benefit by accounting for potential differences in cerebral morphology that exist even after spatial normalization.