Long-range gamma phase synchronization as a compensatory strategy during working memory in high-performing patients with schizophrenia.

Working memory deficits in schizophrenia may be associated with impairments in the integration of neural activity across a distributed network of cortical areas. However, evaluation of the contribution of this integration to working memory impairments in patients is severely confounded by behavioral performance. In the present multidimensional-neuroimaging study, measures of neural oscillations at baseline and during a working memory task, baseline gamma-aminobutyric acid (GABA) level in the left dorsolateral prefrontal cortex (DLPFC), and behavioral performance were obtained. Controlling behavioral performance by recruiting only "high-performing" patients with schizophrenia, we investigated whether the strength of cross-area communications differs between patients with schizophrenia and healthy participants under accurate and equivalent behavioral performance. Results of phase-locking value indicated that these high-performing patients recruited significantly more between frontal and occipital regions in the left hemisphere, t(13) = -2.16, p = .05, Cohen's d = -1.20, and between frontal and temporal regions in the right hemisphere, t(13) = -2.63, p = .02, Cohen's d = -1.46. These cross-area communication patterns may be associated with visuoverbal and visuospatial working memory networks of the left and right hemispheres, respectively. Moreover, correlations of patient's cross-area communication with in vivo GABA levels of the left DLPFC revealed a significant positive relationship (r = .77, p = .04), demonstrating that the critical role of GABA functions in gamma band oscillations may go beyond local neuronal assemblies in the left DLPFC. Altogether, these exploratory findings point to the heterogeneity among schizophrenia patients and highlight the notion that high-performing patients may engage in potential compensatory mechanisms and may represent a subgroup of patients that may be categorically or dimensionally divergent in psychopathology.

Usefulness of proton and phosphorus MR spectroscopic imaging for early diagnosis of Parkinson's disease.

BACKGROUND AND PURPOSE: Cerebral mitochondrial dysfunction has been observed in Parkinson's disease (PD). If mitochondrial dysfunction is an early event contributing to PD development, then noninvasive techniques that detect disturbed energy metabolism in vivo might be useful tools for early diagnosis and treatment monitoring. In the present study, we tested the hypothesis that proton ((1) H) and phosphorus ((31) P) magnetic resonance spectroscopy (MRS) measures of brain metabolites are able to differentiate between individuals with early PD and healthy volunteers (HVs). METHODS: During this cross-sectional study including 20 subjects with early PD and 15 age-matched HV, ventricular lactate (anaerobic glycolysis); and regional levels of N-acetylaspartate (neuronal integrity); choline (membrane turnover); creatine (energy metabolism); ATP and other phosphate-containing compounds (oxidative phosphorylation) were determined using brain (1) H and (31) P MRS. RESULTS: No metabolic abnormalities were detectable in early-stage PD patients. Metabolite concentrations were not related to age, disease duration, or Unified Parkinson's Disease Rating Scale motor scores. DISCUSSION: In early PD, neither (1) H nor (31) P MRS were able to detect metabolic abnormalities, a finding that is in contrast to published data in more advanced PD cohorts. MRS under dynamic conditions might uncover latent energy deficits in early PD, thus warranting future study.

Sex differences in cerebral energy metabolism in Parkinson's disease: a phosphorus magnetic resonance spectroscopic imaging study.

OBJECTIVE: To test the hypothesis that there are sex differences in cerebral energy metabolism in Parkinson's disease (PD). METHODS: Phosphorus magnetic resonance spectroscopy ((31)P MRS) was used to determine high-energy phosphate (phosphocreatine and ATP) and low-energy phosphate (free phosphate) levels in the striatum and temporoparietal cortical gray matter (GM) in 10 men and 10 women with PD, matched for age at onset, disease duration, and UPDRS scores. RESULTS: In the hemisphere more affected by PD, both ATP and high energy phosphate (HEP: phosphocreatine + ATP) content in striatum was 15% lower in men versus women with PD (p = .050 and p = .048, respectively). Similar decreases by 16% in ATP (p = .023) and 12% in HEP (p = .046) were observed in GM in men versus women with PD. In contrast, there were no detectable sex differences in ATP or HEP in healthy age-matched controls. CONCLUSIONS: Men with PD have lower levels of ATP and high energy phosphate than women in brain regions affected by PD. These findings suggest that there may be a greater burden of mitochondrial dysfunction in PD in men versus women with PD.

Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study.

BACKGROUND: On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. OBJECTIVES: To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. METHODS: Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. RESULTS: Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. CONCLUSION: This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.

Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: relationship to IQ and early trauma.

We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers. A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications. We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter. The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations. Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been performed on a 1.5-T MRI. Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls. In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, high IQ was associated with less worry. In all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores. The CSO may therefore represent a neural substrate that exhibits reductions in CHO and CR metabolite concentrations that are inversely associated with GAD symptomatology and, in the case of CHO, with intelligence. These conclusions are deemed preliminary due to small sample size, with further study of cerebral WM in anxiety disorders suggested.

A multicenter study of two magnetic resonance spectroscopy techniques in individuals with HIV dementia.

PURPOSE: To evaluate single-voxel proton magnetic resonance spectroscopy (SV-MRS) and magnetic resonance spectroscopic imaging (MRSI) metabolite results in individuals with HIV dementia. MATERIALS AND METHODS: Twenty HIV-positive (HIV+) individuals underwent SV-MRS (TE 35 msec) and MRSI (TE 280 msec). Results were stratified according to serostatus, dementia severity, psychomotor speed performance, and functional impairment. RESULTS: HIV+ individuals with psychomotor slowing had an increased myoinositol/creatine (mI/Cr) ratio (0.63 vs. 0.45) in the frontal white matter using SV-MRS and an increased choline (Cho)/Cr ratio (1.88 vs. 1.41) in the mesial frontal gray matter using MRSI compared to HIV+ individuals without psychomotor slowing. Using MRSI, subjects with HIV dementia also had a decreased N-acetyl aspartate (NAA)/Cho ratio (1.55 vs. 2.53) compared to HIV+ individuals without cognitive impairment in the mesial frontal gray matter. Both techniques detected metabolite ratio abnormalities associated with abnormal functional performance. CONCLUSION: SV-MRS and MRSI offer complementary roles in evaluating individuals with HIV dementia. Short TE SV-MRS measures mI, which may be elevated in early HIV dementia, whereas MRSI provides wider spatial coverage to examine specific regional changes.