Cortical locations of maximal spindle activity: magnetoencephalography (MEG) study

The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 ± 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole-head 148-channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence.     

Discrimination of AD and normal subjects from MRI: anatomical versus statistical regions

This work is a feature-extraction and classification study between Alzheimer's disease (AD) patients and normal subjects. Voxel-wise morphological features of brain MRI are defined as the Jacobian determinants that measure the local volume change between each subject and a given atlas. The goal of this work is to determine the region of interest (ROI) which is best suited for classification. Two types of ROIs are considered: anatomical regions, that were automatically segmented in the atlas (amygdalae, hippocampi and lateral ventricles); and statistical regions, defined from group comparison statistical maps. Classification performance was assessed with five classifiers on 20 pairs of matched training and test groups of subjects from the ADNI database. In this study the statistical masks provided the best classification performance.     

Cortical processing of near‐threshold tactile stimuli: An MEG study

In the present study we tested the applicability of a paired‐stimulus paradigm for the investigation of near‐threshold (NT) stimulus processing in the somatosensory system using magnetoencephalography. Cortical processing of the NT stimuli was studied indirectly by investigating the impact of NT stimuli on the source activity of succeeding suprathreshold test stimuli. We hypothesized that cortical responses evoked by test stimuli are reduced due to the preactivation of the same finger representation by the preceding NT stimulus. We observed attenuation of the magnetic responses in the secondary somatosensory (SII) cortex, with stronger decreases for perceived than for missed NT stimuli. Our data suggest that processing in the primary somatosensory cortex including recovery lasts for <200 ms. Conversely, the occupancy of SII lasts ≥500 ms, which points to its role in temporal integration and conscious perception of sensory input.     

Cortical activity during speech and non-speech oromotor tasks: A magnetoencephalography (MEG) study

We used whole-head magnetoencephalography to investigate cortical activity during two oromotor activities foundational to speech production. 13 adults performed mouth opening and phoneme (/pa/) production tasks to a visual cue. Jaw movements were tracked with an ultrasound-emitting device. Trials were time-locked to both stimulus onset and peak of jaw displacement. An event-related beamformer source reconstruction algorithm was used to detect areas of cortical activity for each condition. Beamformer output was submitted to iterative K-means clustering analyses. The time course of neural activity at each cluster centroid was computed for each individual and condition. Peaks were identified and latencies submitted for statistical analysis to reveal the relative timing of activity in each brain region. Stimulus locked activations for the mouth open task included a progression from left cuneus to left frontal and then right pre-central gyrus. Phoneme generation revealed the same sequence but with bilateral frontal activation. When time locked to jaw displacement, the mouth open condition showed left frontal followed by right frontal–temporal areas. Phoneme generation showed a complicated sequence of bilateral temporal and frontal areas. This study used three unique approaches (beamforming, clustering and jaw tracking) to demonstrate the temporal progression of neural activations that underlie the motor control of two simple oromotor tasks. These findings have implications for understanding clinical conditions with deficits in articulatory control or motor speech planning.     

Transfer factor: failure to transfer reactivity in normal human subjects.

Transfer factor was prepared from highly selected normal donors. One lot was made from donors strongly reactive to coccidioidin and negative to Dharmendra antigen in in vivo and in vitro testing. The other lot was made from donors without reactivity to coccidioidin and strongly reactive to Dharmendra. Aliquots of each lot were injected into eight normal recipients. Eight additional normal recipients were given placebo injections. Before and after injection, skin test reactivity and in vitro testing were evaluated by an individual who did not know which preparation the patient received. Changes in immunologic reactivity in subjects receiving transfer factor could not be distinguished from those in subjects receiving placebo. I conclude that transfer factor does not cause enhancement of immunologic reactivity in normal subjects. A well designed, critical study is needed to determine whether or not it does, in fact, cause enhancement of immunologic reactivity in patients with impaired cellular immune reactivity.     

Source estimation of spontaneous MEG activity and auditory evoked responses in normal subjects during sleep

Summary This study focuses on source estimation of spontaneous MEG activity and auditory evoked responses during sleep. Sources of K-complexes and auditory evoked responses were investigated by magnetoencephalograph (MEG) and electroencephalograph (EEG) measurements, simultaneously. Sources of K-complexes during stage 2 sleep were investigated. The MEG results suggested that the sources of K-complexes can be modeled by two current dipoles. Dipoles for the K-complexes were estimated to be located 5 mm away from the sources of the N100 components of auditory evoked responses during wakefulness. Sources of auditory evoked responses during each sleep stage were also investigated to clarify the origins of the K-complex, the vertex sharp transient, and delta waves. Estimated dipoles for the N100 component for each sleep stage were estimated to be at slightly different locations in the auditory area. Based upon results of the MEG measurements and the EEG topographies, sources of the N330 component can be modeled by multiple current dipoles, which are seen to be distributed diffusely throughout the cerebral cortex.This work was supported in part by the grant 03505002, from the Ministry of Education Science and Culture, Japan.     

Cortical networks generating movement-related EEG rhythms in Alzheimer's disease: an EEG coherence study

Patients with mild Alzheimer's disease (AD) present with abnormally strong values of frontal and ipsilateral central sensorimotor rhythms. The authors tested 2 working hypotheses of the related electroencephalographic (EEG) coherence: disconnection, defined as a sign of a reduced coordination within the frontoparietal and interhemispheric networks, and cooperation, defined as a reflection of the reorganization of the brain sensorimotor networks. Results showed that, compared with healthy controls, patients with mild AD had an unreactive and abnormally low interhemispheric EEG coherence and an unreactive and abnormally high frontoparietal EEG coherence. These findings support the hypothesis of an impaired mechanism of sensorimotor cortical coupling (disconnection) in mild AD.     

Quantitative relationships between sensitizing dose of DNCB and reactivity in normal subjects

We have developed quantitative methods which enable us to measure susceptibility to sensitization with dinitrochlorobenzene (DNBC) and the degree of responsiveness of groups, and to analyse factors affecting the afferent and efferent components of the response. Five groups of normal subjects (132 individuals) were sensitized with DNCB (1,000, 500, 250, 125 or 62.5 micrograms). One month later, each subject was challenged with 12.5, 6.25 and 3.125 micrograms of DNCB on standard patch test felts. After 48 h the reaction at each challenge site was graded clinically and measured as diameter of induration and increase in skinfold thickness. The proportion of subjects sensitized increased with sensitizing dose; 8% were sensitized by 62.5 and 100% were sensitized by 500 micrograms or more. The 50% sensitizing dose (ED50) was calculated as 116 micrograms. Increase in skinfold thickness proved the best method of assessing response and was linearly related to log challenge dose. There was also a linear relationship between degree of sensitivity and log sensitizing dose so that, on average, each time sensitizing dose was halved, the challenge dose required to produce the same response increased 1.5-fold. These methods can be used to measure sensitizability of a population, the degree of sensitivity and the expression of reactivity. The technique will allow quantitative study of factors altering the induction or expression of such reactivity in disease.     

Cortical drives to human muscle: the Piper and related rhythms

During voluntary activity in humans, motor units are exposed to a number of descending drives that tend to synchronize motor unit activity at particular frequencies. In particular, the contralateral motor cortex drives muscle discharge in the beta (15-30 Hz) and Piper (30-60 Hz) bands. The cortical activity in these bands is task-specific, somatopicly distributed and generally precedes muscle discharge by an interval appropriate for conduction in fast pyramidal pathways. Coherence between cortex and muscle in the beta band is found during isometric contractions of weak to moderate strength. Thus oscillations within the beta band seem to coincide with a stable, relatively immutable state--a free running mode of the motor cortex that may maintain stable motor output with a minimum of computational effort. In contrast, coherence between cortex and muscle in the Piper band is most evident during strong isometric contractions or during movement. Demands on the motor cortex are likely to be greater and more mutable under these circumstances. Synchronisation in the gamma band may provide a means of binding together those particular, often spatially distributed, cortical elements involved in movement execution under conditions that vary from moment to moment and require some attention. Mechanisms both intrinsic and extrinsic to the cortex determine the pattern of rhythmic cortical activity. The basal ganglia have a pivotal role in this regard, and inadequate output from these nuclei leads to a disappearance of the beta and Piper drives to muscle. This may in turn contribute to slowness and weakness in Parkinson's disease.     

Cortical sources of resting state electroencephalographic alpha rhythms deteriorate across time in subjects with amnesic mild cognitive impairment

Cortical sources of resting state electroencephalographic (EEG) rhythms are abnormal in subjects with mild cognitive impairment (MCI). Here, we tested the hypothesis that these sources in amnesic MCI subjects further deteriorate over 1 year. To this aim, the resting state eyes-closed EEG data were recorded in 54 MCI subjects at baseline (Mini Mental State Examination I = 26.9; standard error [SE], 0.2) and at approximately 1-year follow-up (13.8 months; SE, 0.5; Mini Mental State Examination II = 25.8; SE, 0.2). As a control, EEG recordings were also performed in 45 normal elderly and in 50 mild Alzheimer's disease subjects. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10.5 Hz), alpha2 (10.5–13 Hz), beta1 (13–20 Hz), and beta2 (20–30 Hz). Cortical EEG sources were estimated using low-resolution brain electromagnetic tomography. Compared with the normal elderly and mild Alzheimer's disease subjects, the MCI subjects were characterized by an intermediate power of posterior alpha1 sources. In the MCI subjects, the follow-up EEG recordings showed a decreased power of posterior alpha1 and alpha2 sources. These results suggest that the resting state EEG alpha sources were sensitive—at least at the group level—to the cognitive decline occurring in the amnesic MCI group over 1 year, and might represent cost-effective, noninvasive and widely available markers to follow amnesic MCI populations in large clinical trials.     

Personality, manual preference and neuroendocrine reactivity in hirsute subjects

Behavioral and neuroendocrine differences may be postulated in hirsute subjects since central effects of gonadal steroids are well established. We conducted a controlled clinical study with 25 consecutive young hirsute participants compared with 20 consecutive controls. Neuropsychological evaluation included the Minnesota Multiphasic Personality Inventory (MMPI) and the Edinburgh Inventory of Manual Preference (EIMP). Neuroendocrine reactivity was assessed by the adrenocorticotropic hormone (ACTH) and cortisol responses to corticotropin releasing hormone (CRH). Hirsute participants presented a flattened personality profile with lower neurotic triad scores--146 +/- 20 versus 166 +/- 28. Left-hand preference was more common in hirsute participants--4/21 versus 0/20. Decreased ACTH [area under the curve (AUC)--36 +/-2 8 vs. 72 +/- 63 pg/ml h] and cortisol (AUC--18 +/- 4 vs. 25 +/- 10 microg/dl h) responses to CRH were found in the hirsute group. In the hirsute group, higher manual preference scores were associated with lower ACTH responses to CRH, while the opposite association was found in the control group. In the hirsute group, the hyporeactive hypothalamic-pituitary-adrenal (HPA) axis was associated with lower behavior-deviant scores, while in the control group, the hyporeactive HPA axis was associated with more psychopathology. We conclude that personality and HPA axis reactivity are different in hirsute female participants when compared with controls, with a trend for differences regarding handedness. Personality and handedness are differently associated with HPA reactivity. Distinctive features in hirsute participants are probably established very early during ontogenic development.     

Decreased cortical reactivity underlies subjective daytime light sleepiness in healthy subjects: a multichannel near-infrared spectroscopy study

Daytime sleepiness is considered to be one of the main problems in modern society. Of the four aspects of sleepiness, namely, subjective sleepiness, performance decrease, sleep propensity, and arousal decrease, subjective sleepiness is the most difficult to assess. Brain mechanisms underlying subjective light sleepiness in daytime were investigated in healthy subjects using multichannel near-infrared spectroscopy (NIRS), which enables the noninvasive measurement of regional cerebral blood volume (rCBV) changes under natural conditions. Forty right-handed healthy volunteers participated in this study. Relationships were investigated between subjective sleepiness and anxiety, assessed using the Stanford Sleepiness Scale (SSS) and State-Trait Anxiety Inventory (STAI), respectively, and cerebral cortex reactivities assessed as oxygenated and deoxygenated hemoglobin concentration ([oxy-Hb] and [deoxy-Hb], respectively) changes during a verbal fluency task using a 24-channel NIRS machine. SSS score correlated negatively with an [oxy-Hb] increase in the bilateral frontal channels mainly in the middle and last third of the verbal fluency task period. Subjective light daytime sleepiness in healthy subjects is considered to be related to decreased prefrontal reactivities in the later part of cognitive activation.     

How the vestibular system modulates tactile perception in normal subjects: a behavioural and physiological study

Caloric vestibular stimulation (CVS) is a physiological technique demonstrated to transiently improve hemianaesthesia in right brain-damaged patients (Bottini et al. in Exp Brain Res 99(1):164–169, 1994, Nature 376:778–781, 1995, Neurology 65(8):1278–1283, 2005). Recent studies suggest that these effects are based on the anatomical overlapping between vestibular and tactile projections (Bottini et al. in Nature 376:778–781, 1995) in the human brain. However, much less is known about behavioural effects of this manipulation on normal subjects. We aimed to explore tactile perception during left ear CVS in normal subjects. We administered seventeen right-handed normal subjects with different types of tactile stimuli (above and below threshold) during left ear CVS. To further ensure standardized procedure, tactile stimulation was delivered through a tool-developed ad hoc for the experiment. The experiment was divided in 3 conditions: (1) Baseline, (2) PostCVS and (3) Delayed CVS. We found a main effect of stimulus type (F _(2,32) = 907.712; P = 0.000) and condition (F _(2,32) = 55.505; P = 0.000). Moreover, post hoc comparisons revealed that below threshold stimuli are most affected by CVS (t ₍₁₆₎ = −11.213; P = 0.000). Left ear CVS modulates tactile perception also in normal subjects. Moreover, this modulation seems to be selective for below threshold stimuli and not caused by attentive processes. A multisensory phenomenon is possibly the best explanation for this interaction between touch and vestibular systems, corroborated also by the anatomical evidence and by the previous knowledge about interaction with the environment.     

Cortical asymmetries in normal, mild cognitive impairment, and Alzheimer's disease

There are functional and structural neocortical hemispheric asymmetries in people with normal cognition. These asymmetries may be altered in patients with Alzheimer's disease (AD) because there is a loss of neuronal connectivity in the heteromodal cortex. The purpose of this study is to test the hypothesis that individuals with amnestic mild cognitive impairment (aMCI), mild AD, and moderate to severe AD have progressive reductions in thickness asymmetries of the heteromodal neocortex. Right-handed elderly volunteers including normal cognition (NC), aMCI, and AD underwent 3-D volume imaging for cortical thickness. Although the cortical asymmetry pattern observed in normal cognition brains was generally maintained in aMCI and AD, there was a progressive decrease in the degree of asymmetry, especially in the inferior parietal lobule. A reduction of neocortical asymmetries may be a characteristic sign that occurs in patients with AD. Future studies are needed to evaluate whether this loss is specific to AD and if measurements of asymmetry can be used as diagnostic markers and for monitoring disease progression.