Impaired brain activity in cirrhotic patients with minimal hepatic encephalopathy: Evaluation by near-infrared spectroscopy.

AIM: Near-infrared spectroscopy (NIRS) is a tool that could non-invasively measure the regional cerebral oxygenated hemoglobin (oxy-Hb) concentration with high time resolution. The aim of the present study is to reveal the time-dependent regional cerebral oxy-Hb concentration change coupled with brain activity during task performance in patients with minimal hepatic encephalopathy (MHE). METHODS: Cerebral oxy-Hb concentration was measured by using NIRS in 29 cirrhotic patients without overt hepatic encephalopathy (HE). Of those, 16 patients who had abnormal electroencephalography findings were defined as having MHE. Responsive increase in oxy-Hb during a word-fluency task was compared between MHE and non-MHE patients. RESULTS: There was no difference in the maximum value of oxy-Hb increase between patients with and without MHE (0.26 ± 0.12 vs 0.32 ± 0.22 mM·mm, P = 0.37). However, the pattern of the time course changes of oxy-Hb was different between the two groups. The MHE group was characterized by a gradual increase of oxy-Hb throughout the task compared to steep and repetitive increase in the non-MHE group. Increase in oxy-Hb concentration at 5 s after starting the task was significantly small in the MHE group compared to the non-MHE (0.03 ± 0.05 vs 0.11 ± 0.09 mM·mm, P = 0.006). CONCLUSION: The cerebral oxygen concentration is poorly reactive in response to tasks among cirrhotic patients without overt HE but having abnormal electroencephalography findings. These impaired responses in regional cerebral oxy-Hb concentration may be related to the latent impairment of brain activity seen in MHE.

Traveling EEG slow oscillation along the dorsal attention network initiates spontaneous perceptual switching.

An ambiguous figure such as the Necker cube causes spontaneous perceptual switching (SPS). The mechanism of SPS in multistable perception has not yet been determined. Although early psychological studies suggested that SPS may be caused by fatigue or satiation of orientation, the neural mechanism of SPS is still unknown. Functional magnetic resonance imaging (fMRI) has shown that the dorsal attention network (DAN), which mainly controls voluntary attention, is involved in bistable perception of the Necker cube. To determine whether neural dynamics along the DAN cause SPS, we performed simultaneous electroencephalography (EEG) and fMRI during an SPS task with the Necker cube, with every SPS reported by pressing a button. This EEG-fMRI integrated analysis showed that (a) 3-4 Hz spectral EEG power modulation at fronto-central, parietal, and centro-parietal electrode sites sequentially appeared from 750 to 350 ms prior to the button press; and (b) activations correlating with the EEG modulation traveled along the DAN from the frontal to the parietal regions. These findings suggest that slow oscillation initiates SPS through global dynamics along the attentional system such as the DAN.

Subsequent memory-dependent EEG theta correlates to parahippocampal blood oxygenation level-dependent response.

The 4-12 Hz (theta rhythm)-dependent neural dynamics play a fundamental role in the memory formation of the rat hippocampus. Although the power of human scalp electroencephalography theta (EEG theta) is known to be associated with a hippocampus-dependent memory encoding, it remains unclear whether the human hippocampus uses theta rhythm. In this study, we aim to identify the scalp EEG theta-related neural regions during memory encoding by using a simultaneous EEG-functional magnetic resonance imaging recording. We showed that the parahippocampal and the medial frontal and posterior regions were significantly correlated to subsequent memory-dependent EEG theta power. This evidence suggests that the human parahippocampal region and associated structures use theta rhythm during hippocampal memory encoding as in rodents.

Ultrahigh-frequency EEG during fMRI: pushing the limits of imaging-artifact correction.

Although solutions for imaging-artifact correction in simultaneous EEG-fMRI are improving, residual artifacts after correction still considerably affect the EEG spectrum in the ultrafast frequency band above 100 Hz. Yet this band contains subtle but valuable physiological signatures such as fast gamma oscillations or evoked high-frequency (600 Hz) bursts related to spiking of thalamocortical and cortical neurons. Here we introduce a simultaneous EEG-fMRI approach that integrates hard and software modifications for continuous acquisition of ultrafast EEG oscillations during fMRI. Our approach is based upon and extends the established method of averaged artifact subtraction (AAS). Particularly for recovery of ultrahigh-frequency EEG signatures, AAS requires invariantly sampled and constant imaging-artifact waveforms to achieve optimal imaging-artifact correction. Consequently, we adjusted our acquisition setup such that both physiological ultrahigh-frequency EEG and invariantly sampled imaging artifacts were captured. In addition, we extended the AAS algorithm to cope with other, non-sampling related sources of imaging-artifact variations such as subject movements. A cascaded principal component analysis finally removed remaining imaging-artifact residuals. We provide a detailed evaluation of averaged ultrahigh-frequency signals and unaveraged broadband EEG spectra up to 1 kHz. Evoked nanovolt-sized high-frequency bursts were successfully recovered during periods of MR data acquisition afflicted by imaging artifacts in the millivolt range. Compared to periods without imaging artifacts they exhibited the same mean amplitudes, latencies and waveforms and a signal-to-noise ratio of 72%. Furthermore we identified consistent dipole sources. In conclusion, ultrafast EEG oscillations can be continuously monitored during fMRI using the proposed approach.

Stimulus-response profile during single-pulse transcranial magnetic stimulation to the primary motor cortex.

We examined the stimulus-response profile during single-pulse transcranial magnetic stimulation (TMS) by measuring motor-evoked potentials (MEPs) with electromyographic monitoring and hemodynamic responses with functional magnetic resonance imaging (fMRI) at 3 Tesla. In 16 healthy subjects, single TMS pulses were irregularly delivered to the left primary motor cortex at a mean frequency of 0.15 Hz with a wide range of stimulus intensities. The measurement of MEP proved a typical relationship between stimulus intensity and MEP amplitude in the concurrent TMS-fMRI environment. In the population-level analysis of the suprathreshold stimulation conditions, significant increases in hemodynamic responses were detected in the motor/somatosensory network, reflecting both direct and remote effects of TMS, and also the auditory/cognitive areas, perhaps related to detection of clicks. The stimulus-response profile showed both linear and nonlinear components in the direct and remote motor/somatosensory network. A detailed analysis suggested that the nonlinear components of the motor/somatosensory network activity might be induced by nonlinear recruitment of neurons in addition to sensory afferents resulting from movement. These findings expand our basic knowledge of the quantitative relationship between TMS-induced neural activations and hemodynamic signals measured by neuroimaging techniques.

Removal of ballistocardiogram artifacts from simultaneously recorded EEG and fMRI data using independent component analysis.

Simultaneous recording of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has been studied to identify areas related to EEG events. EEG data recorded in the magnetic resonance (MR) scanner with MR imaging is suffered from two specific artifacts, imaging artifact, and ballistocardiogram (BCG). In this paper, we focus on BCG. In preceding studies, average subtraction was often used for this purpose. However, average subtraction requires an assumption that BCG waveforms are precisely periodic, which seems unrealistic because BCG is a biomedical artifact. We propose the application of independent component analysis (ICA) with a postprocessing of high-pass filtering for the removal of BCG. With this approach, it is not necessary to assume that the BCG waveform is periodic. Empirically, we show that our proposed method removes BCG artifacts as well as does the average subtraction method. Power spectral density analysis of the two approaches shows that, with ICA, distortion of recovered EEG data is also as small as that associated with the average subtraction approach. We also propose a hypothesis for how head movement causes BCGs and show why ICA can remove BCG artifacts arising from this source.

Antipsychotic medication and cognitive function in schizophrenia.

Antipsychotic polypharmacy and excessive dosing still prevail worldwide in the treatment of schizophrenia, while their possible association with cognitive function has not well been examined. We examined whether the "non-standard" use of antipsychotics (defined as antipsychotic polypharmacy or dosage >1,000 mg/day of chlorpromazine equivalents) is associated with cognitive function. Furthermore, we compared cognitive function between patients taking only atypical antipsychotics and those taking only conventionals. Neurocognitive functions were assessed in 67 patients with chronic schizophrenia and 92 controls using the Wechsler Memory Scale-Revised (WMS-R), the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Wisconsin Card Sorting Test (WCST), and the Advanced Trail Making Test (ATMT). Patients showed markedly poorer performance than controls on all these tests. Patients on non-standard antipsychotic medication demonstrated poorer performance than those on standard medication on visual memory, delayed recall, performance IQ, and executive function. Patients taking atypical antipsychotics showed better performance than those taking conventionals on visual memory, delayed recall, and executive function. Clinical characteristics such as duration of medication, number of hospitalizations, and concomitant antiparkinsonian drugs were different between the treatment groups (both dichotomies of standard/non-standard and conventional/atypical). These results provide evidence for an association between antipsychotic medication and cognitive function. This association between antipsychotic medication and cognitive function may be due to differential illness severity (e.g., non-standard treatment for severely ill patients who have severe cognitive impairment). Alternatively, poorer cognitive function may be due in part to polypharmacy or excessive dosing. Further investigations are required to draw any conclusions.

The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia.

The catechol-O-methyl transferase (COMT) gene is considered to be a promising schizophrenia susceptibility gene. A common functional polymorphism (Val158Met) in the COMT gene affects dopamine regulation in the prefrontal cortex (PFC). Recent studies suggest that this polymorphism contributes to poor prefrontal functions, particularly working memory, in both normal individuals and patients with schizophrenia. However, possible morphological changes underlying such functional impairments remain to be clarified. The aim of this study was to examine whether the Val158Met polymorphism of the COMT gene has an impact on brain morphology in normal individuals and patients with schizophrenia. The Val158Met COMT genotype was obtained for 76 healthy controls and 47 schizophrenics. The diagnostic effects, the effects of COMT genotype and the genotype-diagnosis interaction on brain morphology were evaluated by using a voxel-by-voxel statistical analysis for high-resolution MRI, a tensor-based morphometry. Patients with schizophrenia demonstrated a significant reduction of volumes in the limbic and paralimbic systems, neocortical areas and the subcortical regions. Individuals homozygous for the Val-COMT allele demonstrated significant reduction of volumes in the left anterior cingulate cortex (ACC) and the right middle temporal gyrus (MTG) compared to Met-COMT carriers. Significant genotype-diagnosis interaction effects on brain morphology were noted in the left ACC, the left parahippocampal gyrus and the left amygdala-uncus. No significant genotype effects or genotype-diagnosis interaction effects on morphology in the dorsolateral PFC (DLPFC) were found. In the control group, no significant genotype effects on brain morphology were found. Schizophrenics homozygous for the Val-COMT showed a significant reduction of volumes in the bilateral ACC, left amygdala-uncus, right MTG and left thalamus compared to Met-COMT schizophrenics. Our findings suggest that the Val158Met polymorphism of the COMT gene might contribute to morphological abnormalities in schizophrenia.

Stepping stone sampling for retrieving artifact-free electroencephalogram during functional magnetic resonance imaging.

Ballistocardiogram and imaging artifacts cause major interference with simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) recording. In particular, the large amplitude of the imaging artifact precludes easy retrieval of EEG signals during fMRI scanning. Recording with 20,000-Hz digitization rate combined with 3000-Hz low-pass filter revealed the real waveform of the imaging artifact, in which it was elucidated that each artifact peak precisely corresponded to each gradient component and actually had differential waveforms of the original gradient pulses. Based on this finding, to retrieve EEG signal during fMRI acquisition, a blip-type echo planar sequence was modified so that EEG sampling might be performed at every 1000 micros (digitization rate 1000 Hz) exclusively in the period in which the artifact resided around the baseline level. This method, called "stepping stone sampling," substantially attenuated the amplitude of the imaging artifact. The remnant of the artifact was subtracted from the averaged artifact waveform. In human studies, alpha activity was successfully retrieved by inspection, and its attenuation/augmentation was observed during eyes open/closed periods. Fast Fourier transform analysis further revealed that even from DC up to 120 Hz, retrieved EEG data during scanning had very similar power distributions to the data retrieved during no scanning, implying the availability of the high-frequency band of the retrieved EEG signals, including even the gamma band.