Early dysfunction of functional connectivity in healthy elderly with subjective memory complaints

It is still an open question whether subjective memory complaints (SMC) can actually be considered to be clinically relevant predictors for the development of an objective memory impairment and even dementia. There is growing evidence that suggests that SMC are associated with an increased risk of dementia and with the presence of biological correlates of early Alzheimer's disease. In this paper, in order to shed some light on this issue, we try to discern whether subjects with SMC showed a different profile of functional connectivity compared with subjects with mild cognitive impairment (MCI) and healthy elderly subjects. In the present study, we compare the degree of synchronization of brain signals recorded with magnetoencephalography between three groups of subjects (56 in total): 19 with MCI, 12 with SMC and 25 healthy controls during a memory task. Synchronization likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. Briefly, results show that subjects with SMC have a very similar pattern of connectivity to control group, but on average, they present a lower synchronization value. These results could indicate that SMC are representing an initial stage with a hypo-synchronization (in comparison with the control group) where the brain system is still not compensating for the failing memory networks, but behaving as controls when compared with the MCI subjects.     

Neural mechanisms of inhibitory control continue to mature in adolescence

Inhibition is a fundamental executive function necessary for self-management of behaviour. The ability to withhold prepotent responses shows protracted development, extending through childhood and into adulthood. Using magnetoencephalography (MEG) with co-registered MRI, the spatiotemporal neural processes involved in inhibitory control were examined in 15 adolescents and 15 adults during a Go/No-go task. Two tasks were run that contained inverse ratios of Go to No-go trials for the experimental (2:1) and control conditions (1:2). Using vector beamforming, images of neural activation between No-go and Go trials were compared for both age-groups and revealed recruitment of the right inferior frontal gyrus in adults (BA 45; 200–250 ms), but delayed recruitment of the left inferior frontal gyri in adolescents (BA 45; 250–300 ms). Left anticipatory-related activity near the hand motor region (BA 6) was present in both adolescents and adults, but for a longer duration in adults. Adolescents additionally recruited the right middle and superior temporal gyri (BA21, BA22), while adults engaged the right temporal gyrus (BA41) but for a much briefer duration. These findings of delayed recruitment of canonical inhibitory control areas with supplementary and prolonged involvement of temporal areas in adolescents compared to adults indicate an immature inhibitory network even in adolescence.     

Variability of magnetoencephalographic sensor sensitivity measures as a function of age,brain volume and cortical area

Objective

To assess the feasibility and appropriateness of magnetoencephalography (MEG) for both adult and pediatric studies, as well as for the developmental comparison of these factors across a wide range of ages.

Methods

For 45 subjects with ages from 1 to 24 years (infants, toddlers, school-age children and young adults), lead fields (LFs) of MEG sensors are computed using anatomically realistic boundary element models (BEMs) and individually-reconstructed cortical surfaces. Novel metrics are introduced to quantify MEG sensor focality.

Results

The variability of MEG focality is graphed as a function of brain volume and cortical area. Statistically significant differences in total cerebral volume, cortical area, MEG global sensitivity and LF focality are found between age groups.

Conclusions

Because MEG focality and sensitivity differ substantially across the age groups studied, the cortical LF maps explored here can provide important insights for the examination and interpretation of MEG signals from early childhood to young adulthood.

Significance

This is the first study to (1) investigate the relationship between MEG cortical LFs and brain volume as well as cortical area across development, and (2) compare LFs between subjects with different head sizes using detailed cortical reconstructions.     

Speech‐in‐noise understanding in older age: The role of inhibitory cortical responses

Studies of central auditory processing underlying speech‐in‐noise (SIN) recognition in aging have mainly concerned the degrading neural representation of speech sound in the auditory brainstem and cortex. Less attention has been paid to the aging‐related decline of inhibitory function, which reduces the ability to suppress distraction from irrelevant sensory input. In a response suppression paradigm, young and older adults listened to sequences of three short sounds during MEG recording. The amplitudes of the cortical P30 response and the 40‐Hz transient gamma response were compared with age, hearing loss and SIN performance. Sensory gating, indicated by the P30 amplitude ratio between the last and the first responses, was reduced in older compared to young listeners. Sensory gating was correlated with age in the older adults but not with hearing loss nor with SIN understanding. The transient gamma response expressed less response suppression. However, the gamma amplitude increased with age and SIN loss. Comparisons of linear multi‐variable modeling showed a stronger brain–behavior relationship between the gamma amplitude and SIN performance than between gamma and age or hearing loss. The findings support the hypothesis that aging‐related changes in the balance between inhibitory and excitatory neural mechanisms modify the generation of gamma oscillations, which impacts on perceptual binding and consequently on SIN understanding abilities. In conclusion, SIN recognition in older age is less affected by central auditory processing at the level of sensation, indicated by sensory gating, but is strongly affected at the level of perceptual organization, indicated by the correlation with the gamma responses.     

Confirmation of Two Magnetoencephalographic Epileptic Foci by Invasive Monitoring from Subdural Electrodes in an Adolescent with Right Frontocentral Epilepsy

PURPOSE: To report our evaluation of interictal two epileptic spike fields on magnetoencephalography (MEG) by using invasive intracranial monitoring in a patient without lesion on magnetic resonance imaging (MRI). METHODS: A 15-year-old left-handed boy with a 9-year history of refractory simple partial seizures, secondarily generalized, and a normal MRI, was studied with MEG to define magnetic spike sources, followed by invasive intracranial monitoring with subdural electrodes to delineate the epileptogenic zone and eloquent function pursuant to focal cortical excision. RESULTS: MEG demonstrated two spike foci on the right middle frontal and inferior rolandic areas adjacent to the sensory area. Ictal recordings during prolonged invasive monitoring from subdural electrodes revealed two epileptogenic zones in the same locations as those defined by MEG. Focal cortical excision was performed of each epileptogenic zone. The patient has been seizure free for 24 months without neurologic deficit. CONCLUSIONS: Magnetic source imaging is a valuable adjunct in the planning of subdural grid placement in epilepsy surgery, particularly in patients in whom conventional imaging fails to reveal a lesion.     

A Comparison of Magnetoencephalography, MRI, and V-EEG in Patients Evaluated for Epilepsy Surgery

PURPOSE: To determine the efficacy and relative contribution of several diagnostic methods [ictal and interictal scalp and intracranial EEG, magnetic resonance imaging (MRI), and magnetoencephalography (MEG)] in identifying the epileptogenic zone for resection. METHODS: This was a prospective study using a masked comparison-to-criterion standard. Fifty-eight consecutive patients with refractory partial epilepsy from two university comprehensive epilepsy programs were studied. Patients who were evaluated for and underwent epilepsy surgery were recruited. The main outcome measure was the efficacy of each diagnostic method to identify the resected epileptogenic zone, when referenced to surgical outcome. RESULTS: MEG (52%) was second only to ictal intracranial V-EEG in predicting the epileptogenic zone for the entire group of patients who had an excellent surgical outcome (seizure free or rare seizure). In a subanalysis, for patients who had temporal lobe surgery, this same relation was seen (MEG, 57%, ictal intracranial V-EEG, 62%). With extratemporal resection, ictal (81%) and interictal (75%) intracranial EEG were superior to MEG (44%) in predicting the surgery site in those patients with an excellent outcome. Finally, for all patients who had a good surgical outcome, MEG (52%) was better than ictal (33%) or interictal (45%) scalp VEEG in predicting the site of surgery. CONCLUSIONS: These results indicate that MEG is a very promising diagnostic method and raise the possibility that it may obviate the need for invasive EEG in some cases or reduce the length of scalp EEG evaluation in others.     

Ictal and Interictal Activity in Partial Epilepsy Recorded with Multichannel Magnetoelectroencephalography: Correlation of Electroencephalography/Electrocorticography, Magnetic Resonance Imaging, Single Photon Emission Computed Tomography, and Positron Emission Tomography Findings

Ictal and interictal epileptic activity was recorded for the first time by multichannel magnetoencephalography (MEG) in three patients with partial epilepsy. Pre- and intra-operative localization of the epileptogenic region was compared. The interictal epileptic activity was localized at the same region of the temporal or frontal lobe as the ictal activity. Main zones of ictal activity were shown to evolve from the tissue at the centers of interictal activity. Pre- and intra-operative electrocorticography (ECoG) as well as postoperative outcome confirmed localization in the temporal and frontal lobe. Results also correlated with findings from scalp EEG, interictal and ictal single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI). Combined multichannel MEG/EEG recording permitted dipole localization of interictal and ictal activity.     

Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson’s disease

ObjectivesDeep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson’s disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation.MethodsPD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31–45 Hz and 55–100 Hz) and induced beta suppression (13–30 Hz). PD patients’ motor symptoms were assessed by UPDRS-III.ResultsUsing Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31–45 Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients’ motor symptoms. Furthermore, treatments did not affect the amplitude of N20m.ConclusionsOur results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms.SignificanceThe differentiated effect suggests differences in the effect mechanisms of the two treatments.     

Acute tryptophan depletion decreases intensity dependence of auditory evoked magnetic N1/P2 dipole source activity

Abstract Rationale. Intensity dependence of the N1/P2 components may be regulated by serotonergic neurons in the primary auditory cortex, where low activity leads to a high intensity dependence and vice versa. Depletion of tryptophan (TRP), a precursor for serotonin has been described to reduce serotonin content in brain of animals and humans. Objective. We investigated the intensity dependence of magnetic and electric N1/P2 components in ten subjects in a double-blind, controlled, cross-over design study after oral mixture of amino-acids leading to acute tryptophan depletion (ATD) and control. Methods. Auditory evoked magnetic fields (AEF) and potentials (AEP) were recorded with 122-channel magnetoencephalography simultaneously with 64-channel EEG 5 h after ingestion of mixtures. The AEF sources and strength were estimated by a least-squares fit of a single equivalent current dipole. The amplitudes and latencies of N1 and P2 recorded with EEG were analyzed at frontal electrode site. Results. TRP depletion decreased the total and free TRP levels by 76 and 45% and control mixture increased it by 48 and 28%. ANOVA showed that ATD had a significant main effect on the N1m/P2m dipole moments at the contralateral (P=0.02), but failed significantly to influence the ipsilateral responses. A significant mixture ingestion-by-stimulus intensity interaction was observed on the N1m/P2m dipole moments at the contralateral hemisphere (P=0.01). The N1/P2 slope for intensity dependence function was decreased following ATD compared with the control experiment (P=0.01) at the contralateral hemisphere. For EEG, a significant mixture ingestion-by-stimulus intensity interaction on the N1 latencies at the Fz electrode position was observed (P=0.01). Conclusion. ATD decreased the intensity dependence of N1m/P2m source dipole moments in the primary auditory cortex at the hemisphere contralateral to the ear stimulated. These results suggest that serotonin participates in the regulation of intensity of auditory stimulation. Electronic Publication