Low single dose gabapentin does not affect prefrontal and occipital gamma-aminobutyric acid concentrations

The γ-aminobutyric acid (GABA) system has been proposed as a target for novel antidepressant and anxiolytic treatments. Emerging evidence suggests that gabapentin (GBP), an anticonvulsant drug that significantly increases brain GABA levels, is effective in the treatment of anxiety disorders. The current study was designed to measure prefrontal and occipital GABA levels in medication-free healthy subjects after taking 0 mg, 150 mg and 300 mg GBP. Subjects were scanned on a 3T scanner using a transmit-receive head coil that provided a relatively homogenous radiofrequency field to obtain spectroscopy measurement in the medial prefrontal (MPFC) and occipital cortex (OCC). There was no dose-dependent effect of GBP on GABA levels in the OCC or MPFC. There was also no effect on Glx, choline or N-acetyl-aspartate concentrations. The previously reported finding of increased GABA levels after GBP treatment is not evident for healthy subjects at the dose of 150 and 300 mg. As a result, if subjects are scanned on a 3T scanner, low dose GPB is not useful as an experimental challenge agent on the GABA system.

Blood-oxygen-level-dependent (BOLD) signal changes in total cortex and subcortex, pain, reward, and vigilance regions during mechanical pressure pain after morphine administration

Morphine is the most common clinical choice in the management of severe pain. Although the molecular mechanisms of morphine have already been characterized, the cerebral circuits by which it attenuates the sensation of pain have not yet been studied in humans. The objective of this two-arm (morphine versus placebo), between-subjects study was to examine whether morphine affects pain via pain-related cortical circuits, but also via reward regions that relate to the motivational state, as well as prefrontal regions that relate to vigilance as a result of morphine's sedative effects. Cortical activity was measured by the blood-oxygen-level-dependent (BOLD) signal changes using functional magnetic resonance imaging (fMRI). ^ The novelty of this study is at three levels: (i) to develop a methodology that will assess the average BOLD signal across subjects for the pain, reward, and vigilance cortical systems; (ii) to examine whether the reward and/or sedative effects of morphine are contributing factors to cortical regions associated with the motivational state and vigilance; and (iii) to propose a neuroanatomical model related to the opioid-sensitive effects of reward and sedation as a function of cortical activity related to pain in an effort to assess future analgesics. ^ Consistent with our hypotheses, our findings showed that the decrease in total pain-related volume activated between the post- and the pre-treatment morphine group was about 78%, while the post-treatment placebo group displayed only a 5% decrease when compared to pre-treatment levels of activation. The volume increase in reward regions was 451% in the post-treatment compared to the pre-treatment morphine condition. Finally, the volumetric decrease in vigilance regions was 63% in the posttreatment compared to the pre-treatment morphine condition. ^ These findings imply that changes in the blood flow of the reward and vigilance regions may be contributing factors in producing the analgesic effect under morphine administration. Future studies need to replicate this study in a higher resolution fMRI environment and to assess the proposed neuroanatomical model in patient populations. The necessity of pain research is apparent, since pain cuts across different diseases especially chronic ones, and thus, is recognized as a vital public health developing area. ^

A study of pyramidal cell structure in the cingulate cortex of the macaque monkey with comparative notes on inferotemporal and primary visual cortex

Recent studies have revealed a marked degree of variation in the pyramidal cell phenotype in visual, somatosensory, motor and prefrontal cortical areas in the brain of different primates, which are believed to subserve specialized cortical function. In the present study we carried out comparisons of dendritic structure of layer III pyramidal cells in the anterior and posterior cingulate cortex and compared their structure with those sampled from inferotemporal cortex (IT) and the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors was determined, and somal areas measured. We found that pyramidal cells in anterior cingulate cortex were more branched and more spinous than those in posterior cingulate cortex, and cells in both anterior and posterior cingulate were considerably larger, more branched, and more spinous than those in area V1. These data show that pyramidal cell structure differs between posterior dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in cingulate cortex have different structure to those in many other cortical areas. These results provide further evidence for a parallel between structural and functional specialization in cortex.

Fractal analysis as a tool for studying specialization in neuronal structure: The study of the evolution of the primate cerebral cortex and human intellect

We review recent findings that, using fractal analysis, have demonstrated systematic regional and species differences in the branching complexity of neocortical pyramidal neurons. In particular, attention is focused on how fractal analysis is being applied to the study of specialization in pyramidal cell structure during the evolution of the primate cerebral cortex. These studies reveal variation in pyramidal cell phenotype that cannot be attributed solely to increasing brain volume. Moreover, the results of these studies suggest that the primate cerebral cortex is composed of neurons of different structural complexity. There is growing evidence to suggest that regional and species differences in neuronal structure influence function at both the cellular and circuit levels. These data challenge the prevailing dogma for cortical uniformity.

Evidence of altered prefrontal-thalamic circuitry in schizophrenia: An optimised diffusion MRI study

MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the diffusion tensor, was used to investigate microstructural changes in the brains of 12 individuals with schizophrenia compared with 12 matched control subjects. To control for the effects of anatomic variation between subject groups, all participants' diffusion images were non-linearly registered to standard anatomical space. Significant statistical differences in mean diffusivity (MD) measures between the two groups were determined on a pixel-by-pixel basis, using Gaussian random field theory. We found significantly elevated MD measures within temporal, parietal and prefrontal cortical regions in the schizophrenia group (P > 0.001), especially within the medial frontal gyrus and anterior cingulate. The dorsal medial and anterior nucleus of the thalamus, including the caudate, also exhibited significantly increased MD in the schizophrenia group (P > 0.001). This study has shown for the first time that MD measures offer an alternative strategy for investigating altered prefrontal-thalamic circuitry in schizophrenia. (c) 2006 Elsevier Inc. All rights reserved.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals (p < 0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p < 0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p < 0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p < 0.02) and neutral faces (p < 0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

Common mode voltage in a motor drive system with PFC

Common mode voltage generated by a power converter in combination with parasitic capacitive couplings is a potential source of shaft voltage in an AC motor drive system. In this paper, a three-phase motor drive system supplied with a single-phase AC-DC diode rectifier is investigated in order to reduce shaft voltage in a three-phase AC motor drive system. In this topology, the common mode voltage generated by the inverter is influenced by the AC-DC diode rectifier because the placement of the neutral point is changing in different rectifier circuit states. A pulse width modulation technique is presented by a proper placement of the zero vectors to reduce the common mode voltage level, which leads to a cost effective shaft voltage reduction technique without load current distortion, while keeping the switching frequency constant. Analysis and simulations have been presented to investigate the proposed method.

Benign Epilepsy with Centro-temporal Spikes: Spike Triggered fMRI Shows Somato-sensory Cortex Activity

Summary:  Objective: We performed spike triggered functional MRI (fMRI) in a 12 year old girl with Benign Epilepsy with Centro-temporal Spikes (BECTS) and left-sided spikes. Our aim was to demonstrate the cerebral origin of her interictal spikes. Methods: EEG was recorded within the 3 Tesla MRI. Whole brain fMRI images were acquired, beginning 2–3 seconds after spikes. Baseline fMRI images were acquired when there were no spikes for 20 seconds. Image sets were compared with the Student's t-test. Results: Ten spike and 20 baseline brain volumes were analysed. Focal activiation was seen in the inferior left sensorimotor cortex near the face area. The anterior cingulate was more active during baseline than spikes. Conclusions: Left sided epileptiform activity in this patient with BECTS is associated with fMRI activation in the left face region of the somatosensory cortex, which would be consistent with the facial sensorimotor involvement in BECT seizures. The presence of BOLD signal change in other regions raises the possibility that the scalp recorded field of this patient with BECTs may reflect electrical change in more than one brain region.

Protein markers for Alzheimer disease in the frontal cortex and cerebellum

Objective: To compare proteins related to Alzheimer disease ( AD) in the frontal cortex and cerebellum of subjects with early-onset AD (EOAD) with or without presenilin 1 (PS1) mutations with sporadic late-onset AD ( LOAD) and nondemented control subjects. Methods: Immunohistochemistry, immunoblot analysis, and ELISA were used to detect and assess protein levels in brain. Results: In EOAD and to a lesser extent in LOAD, there was increased amyloid beta (Abeta) deposition (by immunohistochemistry), increased soluble Abeta (by immunoblot analysis), and specific increases in Abeta(40) and Abeta(42) ( by ELISA) in the frontal cortex and, in some cases, in the cerebellum. Surprisingly, immunoblot analysis revealed reduced levels of PS1 in many of the subjects with EOAD with or without PS1 mutations. In those PS1 mutation-bearing subjects with the highest Abeta, PS1 was barely, if at all, detectable. This decrease in PS1 was specific and not attributable solely to neuronal loss because amyloid precursor protein (APP) and the PS1-interacting protein beta-catenin levels were unchanged. Conclusions: This study shows that in the frontal cortex and cerebellum from Alzheimer disease patients harboring certain presenilin 1 mutations, high levels of amyloid beta are associated with low levels of presenilin 1. The study provides the premise for further investigation of mechanisms underlying the downregulation of presenilin 1, which may have considerable pathogenic and therapeutic relevance.

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

Integrating visual and tactile information in the perirhinal cortex

By virtue of its widespread afferent projections, perirhinal cortex is thought to bind polymodal information into abstract object-level representations. Consistent with this proposal, deficits in cross-modal integration have been reported after perirhinal lesions in nonhuman primates. It is therefore surprising that imaging studies of humans have not observed perirhinal activation during visual-tactile object matching. Critically, however, these studies did not differentiate between congruent and incongruent trials. This is important because successful integration can only occur when polymodal information indicates a single object (congruent) rather than different objects (incongruent). We scanned neurologically intact individuals using functional magnetic resonance imaging (fMRI) while they matched shapes. We found higher perirhinal activation bilaterally for cross-modal (visual-tactile) than unimodal (visual-visual or tactile-tactile) matching, but only when visual and tactile attributes were congruent. Our results demonstrate that the human perirhinal cortex is involved in cross-modal, visual-tactile, integration and, thus, indicate a functional homology between human and monkey perirhinal cortices.

The effect of prior visual information on recognition of speech and sounds

To identify and categorize complex stimuli such as familiar objects or speech, the human brain integrates information that is abstracted at multiple levels from its sensory inputs. Using cross-modal priming for spoken words and sounds, this functional magnetic resonance imaging study identified 3 distinct classes of visuoauditory incongruency effects: visuoauditory incongruency effects were selective for 1) spoken words in the left superior temporal sulcus (STS), 2) environmental sounds in the left angular gyrus (AG), and 3) both words and sounds in the lateral and medial prefrontal cortices (IFS/mPFC). From a cognitive perspective, these incongruency effects suggest that prior visual information influences the neural processes underlying speech and sound recognition at multiple levels, with the STS being involved in phonological, AG in semantic, and mPFC/IFS in higher conceptual processing. In terms of neural mechanisms, effective connectivity analyses (dynamic causal modeling) suggest that these incongruency effects may emerge via greater bottom-up effects from early auditory regions to intermediate multisensory integration areas (i.e., STS and AG). This is consistent with a predictive coding perspective on hierarchical Bayesian inference in the cortex where the domain of the prediction error (phonological vs. semantic) determines its regional expression (middle temporal gyrus/STS vs. AG/intraparietal sulcus).

Anterior temporal cortex and semantic memory : reconciling findings from neuropsychology and functional imaging

Studies of semantic impairment arising from brain disease suggest that the anterior temporal lobes are critical for semantic abilities in humans; yet activation of these regions is rarely reported in functional imaging studies of healthy controls performing semantic tasks. Here, we combined neuropsychological and PET functional imaging data to show that when healthy subjects identify concepts at a specific level, the regions activated correspond to the site of maximal atrophy in patients with relatively pure semantic impairment. The stimuli were color photographs of common animals or vehicles, and the task was category verification at specific (e.g., robin), intermediate (e.g., bird), or general (e.g., animal) levels. Specific, relative to general, categorization activated the antero-lateral temporal cortices bilaterally, despite matching of these experimental conditions for difficulty. Critically, in patients with atrophy in precisely these areas, the most pronounced deficit was in the retrieval of specific semantic information.

Robust control scheme for a microgrid with PFC capacitor connected

Capacitors are widely used for power-factor correction (PFC) in power systems. When a PFC capacitor is installed with a certain load in a microgrid, it may be in parallel with the filter capacitor of the inverter interfacing the utility grid and the local distributed-generation unit and, thus, change the effective filter capacitance. Another complication is the possibility of occurrence of resonance in the microgrid. This paper conducts an in-depth investigation of the effective shunt-filter-capacitance variation and resonance phenomena in a microgrid due to a connection of a PFC capacitor. To compensate the capacitance-parameter variation, an Hinfin controller is designed for the voltage-source- inverter voltage control. By properly choosing the weighting functions, the synthesized Hinfin controller would exhibit high gains at the vicinity of the line frequency, similar to traditional high- performance P+ resonant controller and, thus, would possess nearly zero steady-state error. However, with the robust Hinfin controller, it will be possible to explicitly specify the degree of robustness in face of parameter variations. Furthermore, a thorough investigation is carried out to study the performance of inner current-loop feedback variables under resonance conditions. It reveals that filter-inductor current feedback is more effective in damping the resonance. This resonance can be further attenuated by employing the dual-inverter microgrid conditioner and controlling the series inverter as a virtual resistor affecting only harmonic components without interference with the fundamental power flow. And finally, the study in this paper has been tested experimentally using an experimental microgrid prototype.