Leonides Canuet

Frontal midline theta rhythm and gamma power changes during focused attention on mental calculation: an MEG beamformer analysis

Frontal midline theta rhythm (Fmθ) appears widely distributed over medial prefrontal areas in EEG recordings, indicating focused attention. Although mental calculation is often used as an attention-demanding task, little has been reported on calculation-related activation in Fmθ experiments. In this study we used spatially filtered MEG and permutation analysis to precisely localize cortical generators of the magnetic counterpart of Fmθ, as well as other sources of oscillatory activity associated with mental calculation processing (i.e., arithmetic subtraction). Our results confirmed and extended earlier EEG/MEG studies indicating that Fmθ during mental calculation is generated in the dorsal anterior cingulate and adjacent medial prefrontal cortex. Mental subtraction was also associated with gamma event-related synchronization, as an index of activation, in right parietal regions subserving basic numerical processing and number-based spatial attention. Gamma event-related desynchronization appeared in the right lateral prefrontal cortex, likely representing a mechanism to interrupt neural activity that can interfere with the ongoing cognitive task.

Resting-State EEG Source Localization and Functional Connectivity in Schizophrenia-Like Psychosis of Epilepsy

Background It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits. Methodology/Principal Findings Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called “lagged phase synchronization” was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Brocas area correlating with auditory hallucination scores. Conclusions/Significance In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.

Resting-State Network Disruption and APOE Genotype in Alzheimer's Disease: A lagged Functional Connectivity Study

Background The apolipoprotein E epsilon 4 (APOE-4) is associated with a genetic vulnerability to Alzheimers disease (AD) and with AD-related abnormalities in cortical rhythms. However, it is unclear whether APOE-4 is linked to a specific pattern of intrinsic functional disintegration of the brain after the development of the disease or during its different stages. This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivity in patients with AD, using a physiological connectivity index called “lagged phase synchronization”. Methodology/Principal Findings Resting EEG was recorded during awake, eyes-closed state in 125 patients with AD and 60 elderly controls. Source current density and functional connectivity were determined using eLORETA. Patients with AD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reduced alpha activity in the left inferior parietal and temporo-occipital cortex relative to noncarriers. There was a decreased alpha2 connectivity pattern in AD, involving the left temporal and bilateral parietal cortex. Several brain regions exhibited increased lagged phase synchronization in low frequencies, specifically in the theta band, across and within hemispheres, where temporal lobe connections were particularly compromised. Areas with abnormal theta connectivity correlated with cognitive scores. In patients with early AD, we found an APOE-4-related decrease in interhemispheric alpha connectivity in frontal and parieto-temporal regions. Conclusions/Significance In addition to regional cortical dysfunction, as indicated by abnormal alpha oscillations, there are patterns of functional network disruption affecting theta and alpha bands in AD that associate with the level of cognitive disturbance or with the APOE genotype. These functional patterns of nonlinear connectivity may potentially represent neurophysiological or phenotypic markers of AD, and aid in early detection of the disorder.

Cortical oscillatory power changes during auditory oddball task revealed by spatially filtered magnetoencephalography.

OBJECTIVE To investigate the neural sources and associated changes in oscillatory activity involved in auditory attention and memory updating processing using spatially filtered magnetoencephalography. METHODS We recorded magnetic responses during an auditory oddball task in 12 normal subjects. Synthetic aperture magnetometry (SAM)-permutation analysis was used to visualize the multiple brain regions associated with event-related magnetic fields (ERFs), and event-related oscillations during target detection processing. RESULTS SAM-permutation results showed the topographical distribution of N1m over the bilateral primary auditory cortex. Post-stimulus delta (1.5-4 Hz) activity sources, likely related to the P300 slow-waveform, were distributed over the right frontocentral and parietal regions. Source locations of theta (4-8 Hz) and alpha (8-13 Hz) event-related synchronization (ERS) were identified over the dorsolateral and medial prefrontal cortex. We visualized bilateral central-Rolandic suppresions for mu (8-15 Hz), beta (15-30 Hz), and low-gamma (30-60 Hz) activities, more dominant in the hemisphere contralateral to the moving hand (button-pressing in response to target stimuli). CONCLUSIONS Prefrontal theta and alpha ERS, and frontocentral-parietal delta ERS are functionally engaged in auditory attention and memory updating process. SIGNIFICANCE Spatially filtered MEG is valuable for detection and source localization of task-related changes in the ongoing oscillatory activity during oddball tasks.

Impaired regional hemodynamic response in schizophrenia during multiple prefrontal activation tasks: A two-channel near-infrared spectroscopy study

In schizophrenia, dysfunction of the prefrontal cortex (PFC), regarded as a core feature of the disease, has been investigated by different neuroimaging methods. Near infrared spectroscopy (NIRS), a novel neurophysiological method, is being increasingly used in the investigation of frontal dysfunction in schizophrenia. However, NIRS measurements during multiple frontal activation tasks have been rarely reported. The purpose of this study was to compare hemodynamic changes in the PFC between patients with schizophrenia and healthy controls during four different types of frontal lobe tasks using a 2-channel NIRS system. Thirty patients with schizophrenia and thirty age- and gender-matched healthy controls were enrolled in this study. In both groups, changes in oxygenated hemoglobin concentration (Delta[oxyHb]) at the bilateral forehead were measured during Verbal fluency test letter version (VFT-letter), VFT category version, Tower of Hanoi (TOH), the Sternberg and Stroop tasks. Regarding Delta[oxyHb] in PFC, a diagnosis group effect was found for VFT-letter and TOH. Significant negative correlation was found between left Delta[oxyHb] during TOH and negative and cognitive symptom scores in schizophrenia patients. Right Delta[oxyHb] during TOH also showed significant negative correlation with cognitive symptoms scores. No significant correlation between Delta[oxyHb] and clinical characteristics were observed during VFT-letter. These findings suggest that among a battery of frontal lobe tasks administered to schizophrenia patients, VFT-letter and TOH are more sensitive to detect PFC activation, as indicated by Delta[oxyHb] using a 2-channel NIRS. Taken together, these findings and those of previous neuroimaging studies suggest that VFT-letter and TOH might represent possible candidate physiological markers of prefrontal dysfunction in schizophrenia, though extensive testing in clinical settings will be necessary.

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.

Post-movement beta rebound abnormality as indicator of mirror neuron system dysfunction in autistic spectrum disorder: an MEG study.

The mu rhythm is regarded as a physiological indicator of the human mirror neuron system (MNS). The dysfunctional MNS hypothesis in patients with autistic spectrum disorder (ASD) has often been tested using EEG and MEG, targeting mu rhythm suppression during action observation/execution, although with controversial results. We explored neural activity related to the MNS in patients with ASD, focusing on power increase in the beta frequency band after observation and execution of movements, known as post-movement beta rebound (PMBR). Multiple source beamformer (MSBF) and BrainVoyager QX were used for MEG source imaging and statistical group analysis, respectively. Seven patients with ASD and ten normal subjects participated in this study. During the MEG recordings, the subjects were asked to observe and later execute object-related hand actions performed by an experimenter. We found that both groups exhibited pronounced PMBR exceeding 20% when observing and executing actions with a similar topographic distribution of maximal activity. However, significantly reduced PMBR was found only during the observation condition in the patients relative to controls in cortical regions within the MNS, namely the sensorimotor area, premotor cortex and superior temporal gyrus. Reduced PMBR during the observation condition was also found in the medial prefrontal cortex. These results support the notion of a dysfunctional execution/observation matching system related to MNS impairment in patients with ASD, and the feasibility of using MEG to detect neural activity, in particular PMBR abnormalities, as an index of MNS dysfunction during performance of motor or cognitive tasks.

Discriminant analysis in schizophrenia and healthy subjects using prefrontal activation during frontal lobe tasks: A near-infrared spectroscopy

While psychiatric disorders such as schizophrenia are largely diagnosed on symptomatology, several studies have attempted to determine which biomarkers can discriminate schizophrenia patients from non-patients with schizophrenia. The objective of this study is to assess whether near-infrared spectroscopy (NIRS) measurement can distinguish schizophrenia patients from healthy subjects. Sixty patients with schizophrenia and sixty age- and gender-matched healthy controls were divided into two sequential groups. The concentration change in oxygenated hemoglobin (Delta[oxy-Hb]) was measured in the bilateral prefrontal areas (Fp1-F7 and Fp2-F8) during the Verbal Fluency Test (VFT) letter version and category version, Tower of Hanoi (TOH), Sternbergs (SBT) and Stroop Tasks. In the first group, schizophrenia patients showed poorer task performance on all tasks and less prefrontal cortex activation during all but the Stroop Task compared to healthy subjects. In the second group, schizophrenia patients showed poorer task performance and less prefrontal cortex activation during VFTs and TOH tasks than healthy subjects. We then performed discriminant analysis by a stepwise method using Delta[oxy-Hb] and task performance measures as independent variables. The discriminant analysis in the first group included task performance of TOH, VFT letter and VFT category and Delta[oxy-Hb] of VFT letter. As a result, 88.3% of the participants were correctly classified as being schizophrenic or healthy subjects in the first analysis. The discriminant function derived from the first group correctly assigned 75% of the subjects in the second group. Our findings suggest that NIRS measurement could be applied to differentiate patients with schizophrenia from healthy subjects.

Induced oscillatory responses during the Sternberg's visual memory task in patients with Alzheimer's disease and mild cognitive impairment.

In this study we used magnetoencephalography during a modified version of the Sternbergs memory recognition task performed by patients with early Alzheimers disease (AD), mild cognitive impairment (MCI), and by age-matched healthy controls to identify differences in induced oscillatory responses. For analyses, we focused on the retention period of the working memory task. Multiple-source beamformer and Brain Voyager were used for localization of source-power changes across the cortex and for statistic group analyses, respectively. We found significant differences in oscillatory response during the task, specifically in beta and gamma frequency bands: patients with AD showed reduced beta event-related desynchronization (ERD) in the right central area compared to controls, and reduced gamma ERD in the left prefrontal and medial parietal cortex compared to patients with MCI. Our findings suggest that reduced oscillatory responses over certain brain regions in high frequency bands (i.e., beta, gamma), and especially in the beta band that was significantly different between AD patients and healthy subjects, may represent brain electromagnetic changes underlying visual-object working memory dysfunction in early AD, and a neurophysiological indicator of cognitive decline.

The Default Mode Network is functionally and structurally disrupted in amnestic mild cognitive impairment — A bimodal MEG-DTI study

Over the past years, several studies on Mild Cognitive Impairment (MCI) and Alzheimers disease (AD) have reported Default Mode Network (DMN) deficits. This network is attracting increasing interest in the AD community, as it seems to play an important role in cognitive functioning and in beta amyloid deposition. Attention has been particularly drawn to how different DMN regions are connected using functional or structural connectivity. To this end, most studies have used functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET) or Diffusion Tensor Imaging (DTI). In this study we evaluated (1) functional connectivity from resting state magnetoencephalography (MEG) and (2) structural connectivity from DTI in 26 MCI patients and 31 age-matched controls. Compared to controls, the DMN in the MCI group was functionally disrupted in the alpha band, while no differences were found for delta, theta, beta and gamma frequency bands. In addition, structural disconnection could be assessed through a decreased fractional anisotropy along tracts connecting different DMN regions. This suggests that the DMN functional and anatomical disconnection could represent a core feature of MCI.