George Fein

Effect of Photic Stimulation on Human Visual Cortex Lactate and Phosphates Using 1H and 31P Magnetic Resonance Spectroscopy

Previous animal and human studies showed that photic stimulation (PS) increased cerebral blood flow and glucose uptake much more than oxygen consumption, suggesting selective activation of anaerobic glycolysis. In the present studies, image-guided 1H and 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in lactate and high-energy phosphate concentrations produced by PS of visual cortex in six normal volunteers. PS initially produced a significant rise (to 250% of control, p < 0.01) in visual cortex lactate during the first 6.4 min of PS, followed by a significant decline (p = 0.01) as PS continued. The PCr/Pi ratios decreased significantly from control values during the first 12.8 min of PS (p < 0.05), and the pH was slightly increased. The positive P100 deflection of the visual evoked potential recorded between 100 and 172 ms after the strobe was significantly decreased from control at 12.8 min of PS (p < 0.05). The finding that PS caused decreased PCr/Pi is consistent with the view that increased brain activity stimulated ATPase, causing a rise in ADP that shifted the creatine kinase reaction in the direction of ATP synthesis. The rise in lactate together with an increase in pH suggest that intracellular alkalosis, caused by the shift of creatine kinase, selectively stimulated glycolysis.

Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease

&NA; Article abstract Background The cause of dementia in subcortical ischemic vascular disease (SIVD) is controversial. Objectives To determine whether cognitive impairment in SIVD 1) correlates with measures of ischemic brain injury or brain atrophy, and/or 2) is due to concomitant AD. Methods Volumetric MRI of the brain was performed in 1) elderly subjects with lacunes (L) and a spectrum of cognitive impairment—normal cognition (NC+L, n = 32), mild cognitive impairment (CI+L, n = 26), and dementia (D+L, n = 29); 2) a comparison group with probable AD (n = 28); and 3) a control group with normal cognition and no lacunes (NC). The authors examined the relationship between the severity of cognitive impairment and 1) volume, number, and location of lacunes; 2) volume of white matter signal hyperintensities (WMSH); and 3) measures of brain atrophy (i.e., hippocampal, cortical gray matter, and CSF volumes). Results Among the three lacune groups, severity of cognitive impairment correlated with atrophy of the hippocampus and cortical gray matter, but not with any lacune measure. Although hippocampal atrophy was the best predictor of severity of cognitive impairment, there was evidence for a second, partially independent, atrophic process associated with ventricular dilation, cortical gray matter atrophy, and increase in WMSH. Eight autopsied SIVD cases showed variable severity of ischemic and neurofibrillary degeneration in the hippocampus, but no significant AD pathology in neocortex. The probable AD group gave evidence of only one atrophic process, reflected in the severity of hippocampal atrophy. Comparison of regional neocortical gray matter volumes showed sparing of the primary motor and visual cortices in the probable AD group, but relatively uniform atrophy in the D+L group. Conclusions Dementia in SIVD, as in AD, correlates best with hippocampal and cortical atrophy, rather than any measure of lacunes. In SIVD, unlike AD, there is evidence for partial independence between these two atrophic processes. Hippocampal atrophy may result from a mixture of ischemic and degenerative pathologies. The cause of diffuse cortical atrophy is not known, but may be partially indexed by the severity of WMSH.

Common reference coherence data are confounded by power and phase effects

Coherence analysis of the EEG is used to study the coupling between cortical regions. High coherence between signals recorded at 2 electrodes is interpreted as evidence for neuroanatomic connections between the cortical areas underlying the electrodes. When common reference recordings are used, coherence measures the relationship between 2 time series, each of which is the difference between 2 signals measured at the scalp and is confounded by spectral power and phase at the recording and reference electrodes. Using multi-channel EEG data from 3 subjects, we illustrate the confounding of common reference data coherence computations and demonstrate the extreme effects of power and phase changes on coherence by simulating these changes in the EEG data. Common reference coherence data can be either inflated or deflated as a consequence of activity (i.e., spectral power) at the reference. Phase relationships among the reference and recording time series modulate the power effects on coherence. Both the power and phase effects can vary dramatically across frequencies, having profound and complicated effects on the shape of the coherence function. Based on these considerations, we conclude that common reference coherence data must be interpreted very cautiously and recommend that a new body of EEG coherence data must be gathered using reference-free recording methods before the utility of EEG coherence analysis for understanding brain function can be determined.

P50 suppression is not affected by attentional manipulations

Auditory evoked potentials (EP) to high or moderate intensity, single or paired clicks were recorded from normal young adult subjects. A choice-reaction-time paradigm had two sets of instructions, for intensity discrimination and for number (single versus paired stimulus) discrimination. For intensity discrimination, the second click had no informative value and its N100 amplitude was markedly reduced relative to the first click. For number discrimination, the presence or absence of the second click provided the salient information, and N100 amplitude was actually slightly larger for the second compared to the first click. In contrast, the attentional manipulation had no effect on P50 amplitude, which showed over 50% suppression from the first to the second click for both tasks. Thus, suppression of P50 amplitude to the second of a pair of clicks is insensitive to attentional manipulations that have major effects on N100 amplitude. These findings suggest that abnormalities of schizophrenic P50 suppression reflect neuronal rather than psychological phenomena.

Prefrontal cortical volume reduction associated with frontal cortex function deficit in 6-week abstinent crack-cocaine dependent men

BACKGROUND This study examined regional cortical volumes in 6-week abstinent men dependent on crack-cocaine only (Cr) or on both crack-cocaine and alcohol (CrA). Our goal was to test the a priori hypothesis of prefrontal cortical volume reduction, along with associated impairments in frontal mediated functions, and to look for differences between the Cr and CrA groups. METHODS Structural magnetic resonance imaging (MRI) of the brain and neuropsychological assessment were performed on 17 6-week abstinent Cr subjects, 29 six-week abstinent CrA subjects, and 20 normal controls. Cortical volume was quantified in the prefrontal, parietal, temporal and occipital regions. RESULTS Cr and CrA subjects showed comparable reductions in prefrontal gray matter volume compared to controls; this reduction was negatively associated with performance impairments in the executive function domain. CONCLUSIONS Dependence on Cr (with or without concomitant alcohol dependence) was associated with reduced prefrontal cortical volume. Cr dependence with concomitant alcohol dependence was not associated with greater prefrontal volume reductions than Cr dependence alone. The existence of these findings at 6-week abstinence indicates that they are not a result of acute cocaine or alcohol exposure. The association of reduced prefrontal cortical volume with cognitive impairments in frontal cortex mediated abilities suggests that this reduced cerebral volume has functional consequences.

Neuropsychological performance of individuals dependent on crack-cocaine, or crack-cocaine and alcohol, at 6 weeks and 6 months of abstinence.

BACKGROUND Little data exist on the neuropsychological effects of crack-cocaine dependence or crack-cocaine and alcohol dependence. This study examined cognitive function in abstinent crack dependent and crack and alcohol dependent individuals at 6 weeks and 6 months abstinence. METHODS a comprehensive neuropsychological battery, including the MicroCog computerized assessment, was administered to 20 abstinent crack dependent subjects, 37 abstinent crack and alcohol dependent subjects, and 29 normal controls. Depression was examined as a covariate, and the association between substance use variables and neuropsychological performance was examined. RESULTS the two substance dependent groups had similar neuropsychological profiles at 6 weeks abstinent, with both groups exhibiting significant cognitive impairment in a wide range of functions compared to controls. The substance dependent groups were still impaired significantly at 6 months of abstinence. Only mild effects of depression on neuropsychological performance were observed. CONCLUSIONS crack dependence and crack and alcohol dependence may lead to severe and persistent neuropsychological deficits over a wide range of domains. The strongest predictor of brain damage associated with substance dependence in this sample was dose (particularly quantity and duration of peak dose).

Age-related metabolite changes and volume loss in the hippocampus by magnetic resonance spectroscopy and imaging.

Magnetic resonance imaging (MRI) studies have produced controversial results concerning the correlation of hippocampal volume loss with increasing age. The goals in this study were: 1) to test whether levels of N-acetyl aspartate (NAA, a neuron marker) change in the hippocampus during normal aging and 2) to determine the relationship between hippocampal NAA and volume changes. Proton magnetic resonance spectroscopic imaging (1H MRSI) and MRI were used to measure hippocampal metabolites and volumes in 24 healthy adults from 36 to 85 years of age. NAA/Cho decreased by 24% (r = 0.53, p = 0.01) and NAA/Cr by 26% (r = 0.61, p < 0.005) over the age range studied, whereas Cho/Cr remained stable, implying diminished NAA levels. Hippocampal volume shrank by 20% (r = 0.64, p < 0.05). In summary, aging effects must be considered in 1H MRSI brain studies. Furthermore, because NAA is considered a marker of neurons, these results provide stronger support for neuron loss in the aging hippocampus than volume measurements by MRI alone.

EEG coherence in unmedicated schizophrenic patients

We have recently shown that electroencephalogram (EEG) coherence data recorded with common reference methods, including those obtained from schizophrenics, are confounded by power and phase effects. Three published reports using bipolar recordings found that EEG coherence was higher in schizophrenics; however, only medicated patients were studied. To extend these findings, we measured EEG coherence from bipolar EEG recordings in unmedicated schizophrenics (n = 10), affective disorder patients (n = 8), and normal controls (n = 13) during resting and task conditions. Seven schizophrenics were restudied after a period of neuroleptic treatment. Schizophrenics had higher across-task interhemispheric (p less than 0.05) and intrahemispheric (p less than 0.04) coherence in the theta band and tended to have higher intrahemispheric alpha coherence (p less than 0.08). Medication treatment was associated with clinical improvement and increases in spectral power, but not with changes in coherence values. These results confirm those obtained by earlier investigations and suggest that increased coherence reflects the presence of anomalous cortical organization in schizophrenics rather than medication effects or transient states related to acute clinical disturbance.

Decreased temporal lobe phosphomonoesters in bipolar disorder

In vivo [31P]magnetic resonance spectroscopic imaging ([31P]MRSI) was performed on 12 unmedicated, euthymic bipolar patients and 14 control subjects to determine if there were alterations in high-energy P metabolism in the temporal lobes of bipolar patients. Compared with the control group, the patients with bipolar disorder demonstrated significantly lower phosphomonoesters (PME) in both the left and right temporal lobes. No other group differences in P metabolites or lateralized asymmetries were noted. This preliminary study provides support for altered temporal lobe phospholipid metabolism in bipolar disorder.

31Phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in chronic schizophrenia

In vivo 31Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) was performed on 20 chronic schizophrenic patients and 16 normal controls to determine if there were specific changes in high energy phosphorus and phospholipid metabolism in the frontal lobes of schizophrenic patients. Phosphorous metabolites were assessed in each of the left and right frontal as well as the left and right parietal lobes. Frontal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated higher phosphodiesters (PDE) and lower phosphocreatine (PCr) in both the left and right frontal regions compared to controls. There was also lower left frontal inorganic phosphate (Pi) in the schizophrenic group. No group differences were noted in the left or right parietal regions. In addition, right frontal PDE and right frontal PCr were highly correlated with the hostility-suspiciousness and anxiety-depression subscales of the BPRS. This study provides further support for altered frontal lobe phosphorous metabolism in schizophrenia.