The periaqueductal gray as a critical site to mediate reward seeking during predatory hunting

Previous studies using morphine-treated dams reported a role for the rostral lateral periaqueductal gray (rIPAG) in the behavioral switching between nursing and insect hunting, likely to depend on an enhanced seeking response to the presence of an appetitive rewarding cue (i.e., the roach). To elucidate the neural mechanisms mediating such responses, in the present study, we first observed how the rIPAG influences predatory hunting in male rats. Our behavioral observations indicated that bilateral rIPAG NMDA lesions dramatically interfere with prey hunting, leaving the animal without chasing or attacking the prey, but do not seem to affect the general levels of arousal, locomotor activity and regular feeding. Next, using Phaseolus vulgaris-leucoagglutinin (PHA-L), we have reviewed the rIPAG connection pattern, and pointed out a particularly dense projection to the hypothalamic orexinergic cell group. Double labeled PHA-L and orexin sections showed an extensive overlap between PHA-L labeled fibers and orexin cells, revealing that both the medial/perifornical and lateral hypothalamic orexinergic cell groups receive a substantial innervation from the rIPAG. We have further observed that both the medial/perifornical and lateral hypothalamic orexinergic cell groups up-regulate Fos expression during prey hunting, and that rIPAG lesions blunted this Fos increase only in the lateral hypothalamic, but not in the medial/perifornical, orexinergic group, a finding supposedly associated with the lack of motivational drive to actively pursue the prey. Overall, the present results suggest that the rIPAG should exert a critical influence on reward seeking by activating the lateral hypothalamic orexinergic cell group. (C) 2011 Elsevier B.V. All rights reserved.

Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naive patients

Background: Clinical and sociodemographic findings have supported that OCD is heterogeneous and composed of multiple potentially overlapping and stable symptom dimensions. Previous neuroimaging investigations have correlated different patterns of OCD dimension scores and gray matter (GM) volumes. Despite their relevant contribution, some methodological limitations, such as patient's previous medication intake, may have contributed to inconsistent findings. Method: Voxel-based morphometry was used to investigate correlations between regional GM volumes and symptom dimensions severity scores in a sample of 38 treatment-naive OCD patients. Several standardized instruments were applied, including an interview exclusively developed for assessing symptom dimensions severity (DY-BOCS). Results: Scores on the "aggression" dimension were positively correlated with GM volumes in lateral parietal cortex in both hemispheres and negatively correlated with bilateral insula, left putamen and left inferior OFC. Scores on the "sexual/religious" dimension were positively correlated with GM volumes within the right middle lateral OFC and right DLPFC and negatively correlated with bilateral ACC. Scores on the "hoarding" dimension were positively correlated with GM volumes in the left superior lateral OFC and negatively correlated in the right parahippocampal gyrus. No significant correlations between GM volumes and the "contamination" or "symmetry" dimensions were found. Conclusions: Building upon preexisting findings, our data with treatment-naive OCD patients have demonstrated distinct GM substrates implicated in both cognitive and emotion processing across different OCS dimensions. (C) 2012 Elsevier Ltd. All rights reserved.

Differential role of CB1 and TRPV1 receptors on anandamide modulation of defensive responses induced by nitric oxide in the dorsolateral periaqueductal gray

CB1, TRPV1 and NO can regulate glutamate release and modify defensive behaviors in regions related to defensive behavior such as the dorsolateral periaqueductal gray (dIPAG). A possible interaction between the endocannabinoid and nitrergic systems in this area, however, has not been investigated yet. The objective of the present work was to verify if activation of CB1 or TRPV1 receptors could interfere in the flight responses induced in rats by the injection of SIN-1, an NO donor, into the dIPAG. The results showed that local administration of a low dose (5 pmol) of anandamide (AEA) attenuated the flight responses, measured by the total distance moved and maximum speed in an open arena, induced by intra-dIPAG microinjection of SIN-1 (150 nmol). URB597 (0.1 nmol), an inhibitor of anandamide metabolism, produced similar effects. When animals were locally treated with the CB1 receptor antagonist AM251 the effective AEA dose (5 pmol) increased, rather than decreased, the flight reactions induced by SIN1-1. Higher (50-200 nmol) doses of AEA were ineffective and even tended to potentiate the SIN-1 effect. The TRPV1 antagonist capsazepine (CPZ, 30 nmol) prevented SIN-1 effects and attenuated the potentiation of its effect by the higher (200 nmol) AEA dose. The results indicate that AEA can modulate in a dual way the pro-aversive effects of NO in the dIPAG by activating CB1 or TRPV1 receptors. (C) 2012 Elsevier Ltd. All rights reserved.

Gray matter volume differences specific to formal thought disorder in schizophrenia

Formal thought disorder (FTD) is one of the main symptoms of schizophrenia. To date there are no whole brain volumetric studies investigating gray matter (GM) differences specifically associated with FTD. Here, we studied 20 right-handed schizophrenia patients that differed in the severity of formal thought disorder and 20 matched healthy controls, using voxel-based morphometry (VBM). The severity of FTD was measured with the Scale for the Assessment of Thought, Language, and Communication. The severity was negatively correlated with the GM volume of the left superior temporal sulcus, the left temporal pole, the right middle orbital gyrus and the right cuneus/lingual gyrus. Structural abnormalities specific for FTD were found to be unrelated to GM differences associated with schizophrenia in general. The specific GM abnormalities within the left temporal lobe may help to explain language disturbances included in FTD.

Chronic Pelvic Pain Syndrome in Men is Associated with Reduction of Relative Gray Matter Volume in the Anterior Cingulate Cortex Compared to Healthy Controls

Although chronic pelvic pain syndrome impairs the life of millions of people worldwide, the exact pathomechanisms involved remain to be elucidated. As with other chronic pain syndromes, the central nervous system may have an important role in chronic pelvic pain syndrome. Thus, we assessed brain alterations associated with abnormal pain processing in patients with chronic pelvic pain syndrome.

Reduced Cerebral Blood Flow Within the Default-Mode Network and Within Total Gray Matter in Major Depression

The default-mode network (DMN) was shown to have aberrant blood oxygenation-level-dependent (BOLD) activity in major depressive disorder (MDD). While BOLD is a relative measure of neural activity, cerebral blood flow (CBF) is an absolute measure. Resting-state CBF alterations have been reported in MDD. However, the association of baseline CBF and CBF fluctuations is unclear in MDD. Therefore, the aim was to investigate the CBF within the DMN in MDD, applying a strictly data-driven approach. In 22 MDD patients and 22 matched healthy controls, CBF was acquired using arterial spin labeling (ASL) at rest. A concatenated independent component analysis was performed to identify the DMN within the ASL data. The perfusion of the DMN and its nodes was quantified and compared between groups. The DMN was identified in both groups with high spatial similarity. Absolute CBF values within the DMN were reduced in MDD patients (p<0.001). However, after controlling for whole-brain gray matter CBF and age, the group difference vanished. In patients, depression severity was correlated with reduced perfusion in the DMN in the posterior cingulate cortex and the right inferior parietal lobe. Hypoperfusion within the DMN in MDD is not specific to the DMN. Still, depression severity was linked to DMN node perfusion, supporting a role of the DMN in depression pathobiology. The finding has implications for the interpretation of BOLD functional magnetic resonance imaging data in MDD.

Ventral striatum gray matter density reduction in patients with schizophrenia and psychotic emotional dysregulation

INTRODUCTION: Substantial heterogeneity remains across studies investigating changes in gray matter in schizophrenia. Differences in methodology, heterogeneous symptom patterns and symptom trajectories may contribute to inconsistent findings. To address this problem, we recently proposed to group patients by symptom dimensions, which map on the language, the limbic and the motor systems. The aim of the present study was to investigate whether patients with prevalent symptoms of emotional dysregulation would show structural neuronal abnormalities in the limbic system. METHOD: 43 right-handed medicated patients with schizophrenia were assessed with the Bern Psychopathology Scale (BPS). The patients and a control group of 34 healthy individuals underwent structural imaging at a 3T MRI scanner. Whole brain voxel-based morphometry (VBM) was compared between patient subgroups with different severity of emotional dysregulation. Group comparisons (comparison between patients with severe emotional dysregulation, patients with mild emotional dysregulation, patients with no emotional dysregulation and healthy controls) were performed using a one way ANOVA and ANCOVA respectively. RESULTS: Patients with severe emotional dysregulation had significantly decreased gray matter density in a large cluster including the right ventral striatum and the head of the caudate compared to patients without emotional dysregulation. Comparing patients with severe emotional dysregulation and healthy controls, several clusters of significant decreased GM density were detected in patients, including the right ventral striatum, head of the caudate, left hippocampus, bilateral thalamus, dorsolateral prefrontal and orbitofrontal cortex. The significant effect in the ventral striatum was lost when patients with and without emotional dysregulation were pooled and compared with controls. DISCUSSION: Decreased gray matter density in a large cluster including the right ventral striatum was associated with severe symptoms of emotional dysregulation in patients with schizophrenia. The ventral striatum is an important part of the limbic system, and was indicated to be involved in the generation of incentive salience and psychotic symptoms. Only patients with severe emotional dysregulation had decreased gray matter in several brain structures associated with emotion and reward processing compared to healthy controls. The results support the hypothesis that grouping patients according to specific clinical symptoms matched to the limbic system allows identifying patient subgroups with structural abnormalities in the limbic network.

Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry.

Tensor based morphometry (TBM) was applied to determine the atrophy of deep gray matter (DGM) structures in 88 relapsing multiple sclerosis (MS) patients. For group analysis of atrophy, an unbiased atlas was constructed from 20 normal brains. The MS brain images were co-registered with the unbiased atlas using a symmetric inverse consistent nonlinear registration. These studies demonstrate significant atrophy of thalamus, caudate nucleus, and putamen even at a modest clinical disability, as assessed by the expanded disability status score (EDSS). A significant correlation between atrophy and EDSS was observed for different DGM structures: (thalamus: r=-0.51, p=3.85 x 10(-7); caudate nucleus: r=-0.43, p=2.35 x 10(-5); putamen: r=-0.36, p=6.12 x 10(-6)). Atrophy of these structures also correlated with 1) T2 hyperintense lesion volumes (thalamus: r=-0.56, p=9.96 x 10(-9); caudate nucleus: r=-0.31, p=3.10 x 10(-3); putamen: r=-0.50, p=6.06 x 10(-7)), 2) T1 hypointense lesion volumes (thalamus: r=-0.61, p=2.29 x 10(-10); caudate nucleus: r=-0.35, p=9.51 x 10(-4); putamen: r=-0.43, p=3.51 x 10(-5)), and 3) normalized CSF volume (thalamus: r=-0.66, p=3.55 x 10(-12); caudate nucleus: r=-0.52, p=2.31 x 10(-7), and putamen: r=-0.66, r=2.13 x 10(-12)). More severe atrophy was observed mainly in thalamus at higher EDSS. These studies appear to suggest a link between the white matter damage and DGM atrophy in MS.

DTI and VBM reveal white matter changes without associated gray matter changes in patients with idiopathic restless legs syndrome

BACKGROUND AND PURPOSE We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease. METHODS Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). RESULTS Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations. CONCLUSIONS We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS.

A universal scaling law between gray matter and white matter of cerebral cortex

Neocortex, a new and rapidly evolving brain structure in mammals, has a similar layered architecture in species over a wide range of brain sizes. Larger brains require longer fibers to communicate between distant cortical areas; the volume of the white matter that contains long axons increases disproportionally faster than the volume of the gray matter that contains cell bodies, dendrites, and axons for local information processing, according to a power law. The theoretical analysis presented here shows how this remarkable anatomical regularity might arise naturally as a consequence of the local uniformity of the cortex and the requirement for compact arrangement of long axonal fibers. The predicted power law with an exponent of 4/3 minus a small correction for the thickness of the cortex accurately accounts for empirical data spanning several orders of magnitude in brain sizes for various mammalian species, including human and nonhuman primates.

White and gray matter development in human fetal, newborn and pediatric brains

Brain anatomy is characterized by dramatic growth from the end of the second trimester through the neonatal stage. The characterization of normal axonal growth of the white matter tracts has not been well-documented to date and could provide important clues to understanding the extensive inhomogeneity of white matter injuries in cerebral palsy (CP) patients. However, anatomical studies of human brain development during this period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor magnetic resonance imaging (DTMRI) can reveal detailed anatomy of white matter. We acquired diffusion tensor images (DTI) of postmortem fetal brain samples and in vivo neonates and children. Neural structures were annotated in two-dimensional (2D) slices, segmented, measured, and reconstructed three-dimensionally (3D). The growth status of various white matter tracts was evaluated on cross-sections at 19-20 gestational weeks, and compared with 0-month-old neonates and 5- to 6-year-old children. Limbic, commissural, association, and projection white matter tracts and gray matter structures were illustrated in 3D and quantitatively characterized to assess their dynamic changes. The overall pattern of the time courses for the development of different white matter is that limbic fibers develop first and association fibers last and commissural and projection fibers are forming from anterior to posterior part of the brain. The resultant DTNIRI-based 3D human brain data will be a valuable resource for human brain developmental study and will provide reference standards for diagnostic radiology of premature newborns. (c) 2006 Elsevier Inc. All rights reserved.