Cingulate and thalamic metabolites in obsessive-compulsive disorder.

Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity.

Diminished gray matter within the hypothalamus in autism disorder: a potential link to hormonal effects?

BACKGROUND: Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ, and gender of affected subjects. However, brain changes due to age, IQ, and gender might pose potential confounds in autism neuroimaging analyses. METHODS: To investigate gray matter differences in autism that are not related to these potential confounds, we performed a voxel-based morphometry analysis in 52 affected children and adolescents and 52 matched control subjects. RESULTS: We observed diminished gray matter in a region of the hypothalamus, which synthesizes the behaviorally relevant hormones oxytocin and arginine vasopressin. CONCLUSIONS: This finding provides support for further investigations of the theory of abnormal functioning of this hormonal system in autism and potentially for experimental therapeutic approaches with oxytocin and related neuropeptides.

White matter connectivity of human hypothalamus.

The macroscopic extrinsic white matter connectivity and the internal structure of the hypothalamus are still incompletely defined in humans. We investigated whether in-vivo diffusion tensor imaging tractography provides evidence of systematization according to hypothalamic compartmentalization. Six defined hypothalamic macroscopic compartments, preoptic, supraoptic, anteroventral, anterodorsal, lateral and posterior, were probed, within the right and left hemispheres of 14 subjects. Important new insights into the macroscopic structure of hypothalamus and white matter connections were found; the preoptic, anteroventral, lateral and posterior compartments are strongly connected to the cortex. The anteroventral connects particularly to the prefrontal cortex while the preoptic compartment connects mainly to the deep anterior brain. The anterodorsal connects mainly to the medial thalamus and the midline gray matter. There is a rightward frontal trend of hemispheric connectivity for the preoptic, anteroventral and lateral compartments. These findings may aid new neuromodulation applications and understanding in brain connectomics.

1H MRSI evidence of metabolic abnormalities in childhood-onset schizophrenia.

In adult schizophrenia, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have revealed volumetric and metabolic defects in multiple brain regions, among them the anterior cingulate, frontal cortex, striatum, thalamus, parietal cortex, and frontal and parietal white matter. This study used proton magnetic resonance spectroscopic imaging ((1)H MRSI) to identify potential metabolic abnormalities in these regions in childhood-onset schizophrenia. (1)H MRSI was acquired at 1.5 T and 272 ms echo time in 11 children and adolescents with schizophrenia (aged 7-18 years; seven boys, four girls; all but two medicated) and 20 age-matched healthy controls (10 boys, 10 girls). Absolute levels of N-acetyl compounds (NAA), creatine plus phosphocreatine (Cr), and choline compounds (Cho) were compared among groups in each region. In schizophrenic patients relative to controls, Cr was 14.3% higher in superior anterior cingulate (mean of left and right hemispheres). Cho was higher in superior anterior cingulate (30.3%), frontal cortex (13.3%), and caudate head (13.5%). In the thalamus, there was also a diagnosis-by-gender interaction, whereby NAA was lower in patients for male but not for female subjects. Elevated Cr suggests abnormal local cell-energy demand and elevated Cho is consistent with a prior proposal that patients with early age-of-onset schizophrenia exhibit phospholipid membrane disturbances. Low NAA may reflect diminished neuronal integrity.