Dynamic BOLD functional connectivity in humans and its electrophysiological correlates

Neural oscillations subserve many human perceptual and cognitive operations. Accordingly, brain functional connectivity is not static in time, but fluctuates dynamically following the synchronization and desynchronization of neural populations. This dynamic functional connectivity has recently been demonstrated in spontaneous fluctuations of the Blood Oxygen Level-Dependent (BOLD) signal, measured with functional Magnetic Resonance Imaging (fMRI). We analyzed temporal fluctuations in BOLD connectivity and their electrophysiological correlates, by means of long (≈50 min) joint electroencephalographic (EEG) and fMRI recordings obtained from two populations: 15 awake subjects and 13 subjects undergoing vigilance transitions. We identified positive and negative correlations between EEG spectral power (extracted from electrodes covering different scalp regions) and fMRI BOLD connectivity in a network of 90 cortical and subcortical regions (with millimeter spatial resolution). In particular, increased alpha (8-12 Hz) and beta (15-30 Hz) power were related to decreased functional connectivity, whereas gamma (30-60 Hz) power correlated positively with BOLD connectivity between specific brain regions. These patterns were altered for subjects undergoing vigilance changes, with slower oscillations being correlated with functional connectivity increases. Dynamic BOLD functional connectivity was reflected in the fluctuations of graph theoretical indices of network structure, with changes in frontal and central alpha power correlating with average path length. Our results strongly suggest that fluctuations of BOLD functional connectivity have a neurophysiological origin. Positive correlations with gamma can be interpreted as facilitating increased BOLD connectivity needed to integrate brain regions for cognitive performance. Negative correlations with alpha suggest a temporary functional weakening of local and long-range connectivity, associated with an idling state

Spontaneous Fluctuations in Posterior α-Band EEG Activity Reflect Variability in Excitability of Human Visual Areas

Neural activity fluctuates dynamically with time, and these changes have been reported to be of behavioral significance, despite occurring spontaneously. Through electroencephalography (EEG), fluctuations in α-band (8-14 Hz) activity have been identified over posterior sites that covary on a trial-by-trial basis with whether an upcoming visual stimulus will be detected or not. These fluctuations are thought to index the momentary state of visual cortex excitability. Here, we tested this hypothesis by directly exciting human visual cortex via transcranial magnetic stimulation (TMS) to induce illusory visual percepts (phosphenes) in blindfolded participants, while simultaneously recording EEG. We found that identical TMS-stimuli evoked a percept (P-yes) or not (P-no) depending on prestimulus α-activity. Low prestimulus α-band power resulted in TMS reliably inducing phosphenes (P-yes trials), whereas high prestimulus α-values led the same TMS-stimuli failing to evoke a visual percept (P-no trials). Additional analyses indicated that the perceptually relevant fluctuations in α-activity/visual cortex excitability were spatially specific and occurred on a subsecond time scale in a recurrent pattern. Our data directly link momentary levels of posterior α-band activity to distinct states of visual cortex excitability, and suggest that their spontaneous fluctuation constitutes a visual operation mode that is activated automatically even without retinal inpu

Effects of Repetitive Transcranial Magnetic Stimulation on Spike Pattern and Topography in Patients with Focal Epilepsy

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive method for brain stimulation. Group-studies applying rTMS in epilepsy patients aiming to decrease epileptic spike- or seizure-frequency have led to inconsistent results. Here we studied whether therapeutic trains of rTMS have detectable effects on individual spike pattern and/or frequency in patients suffering from focal epilepsy. Five patients with focal epilepsy underwent one session of rTMS online with EEG using a 6Hz prime/1Hz rTMS protocol (real and sham). The EEG was recorded continuously throughout the stimulation, and the epileptic spikes recorded immediately before (baseline) and after stimulation (sham and real) were subjected to further analysis. Number of spikes, spike-strength and spike-topography were examined. In two of the five patients, real TMS led to significant changes when compared to baseline and sham (decrease in spike-count in one patient, change in topography of the after-discharge in the other patient). Spike-count and topography remained unchanged the remaining patients. Overall, our results do not indicate a consistent effect of rTMS stimulation on interictal spike discharges, but speak in favor of a rather weak and individually variable immediate effect of rTMS on focal epileptic activity. The individuation of most effective stimulation patterns will be decisive for the future role of rTMS in epilepsies and needs to be determined in larger studie

Neuronal networks in children with continuous spikes and waves during slow sleep

Epileptic encephalopathy with continuous spikes and waves during slow sleep is an age-related disorder characterized by the presence of interictal epileptiform discharges during at least >85% of sleep and cognitive deficits associated with this electroencephalography pattern. The pathophysiological mechanisms of continuous spikes and waves during slow sleep and neuropsychological deficits associated with this condition are still poorly understood. Here, we investigated the haemodynamic changes associated with epileptic activity using simultaneous acquisitions of electroencephalography and functional magnetic resonance imaging in 12 children with symptomatic and cryptogenic continuous spikes and waves during slow sleep. We compared the results of magnetic resonance to electric source analysis carried out using a distributed linear inverse solution at two time points of the averaged epileptic spike. All patients demonstrated highly significant spike-related positive (activations) and negative (deactivations) blood oxygenation-level-dependent changes (P < 0.05, family-wise error corrected). The activations involved bilateral perisylvian region and cingulate gyrus in all cases, bilateral frontal cortex in five, bilateral parietal cortex in one and thalamus in five cases. Electrical source analysis demonstrated a similar involvement of the perisylvian brain regions in all patients, independent of the area of spike generation. The spike-related deactivations were found in structures of the default mode network (precuneus, parietal cortex and medial frontal cortex) in all patients and in caudate nucleus in four. Group analyses emphasized the described individual differences. Despite aetiological heterogeneity, patients with continuous spikes and waves during slow sleep were characterized by activation of the similar neuronal network: perisylvian region, insula and cingulate gyrus. Comparison with the electrical source analysis results suggests that the activations correspond to both initiation and propagation pathways. The deactivations in structures of the default mode network are consistent with the concept of epileptiform activity impacting on normal brain function by inducing repetitive interruptions of neurophysiological functio

Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluatio

Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluatio

Literatur-Rundschau

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Accuracy of EEG source imaging of epileptic spikes in patients with large brain lesions

OBJECTIVE: To test the accuracy of EEG source imaging in epilepsy patients with large cerebral lesions. It is hypothesized that lesions are most likely to change conductivity properties and to significantly impair the accuracy of electromagnetic source imaging (ESI) based on the EEG. This has, however, not been tested in patients' EEG. METHODS: Fourteen patients with focal epilepsy and large cerebral lesions underwent high-resolution (128-256 channels) interictal EEG recordings. Thirteen patients were operated, leading to seizure freedom in 12. The spike sources were localized with a distributed linear inverse solution (LAURA) and compared to the post-operative MRI or the results of other invasive or non-invasive exams. RESULTS: In 12 patients ESI indicated the maximum source of the epileptic activity to be located within the epileptogenic zone (85%). One of the remaining cases was not seizure free after surgery. According to the ESI result, however, the focus was incompletely removed. CONCLUSION: High resolution ESI constrained to the individual anatomy identifies the epileptogenic focus in patients with volume relevant brain lesions with excellent accuracy, comparable to that of other non-invasive methods. SIGNIFICANCE: Our results are of particular clinical importance, as they show that ESI can be extended to patients with large inhomogeneous lesions

Increasing the diagnostic value of evoked potentials in multiple sclerosis by quantitative topographic analysis of multichannel recordings

SUMMARY: This study presents a method to record and analyze multichannel visual-evoked potential (VEP) and somatosensory-evoked potential (SEP) in an objective, automatic, and quantitative manner. The intention of this study was to assess their diagnostic value in multiple sclerosis (MS). A 256-channel VEP and SEP were recorded in 44 healthy subjects, 26 patients with MS, and 20 patients with other neurologic diseases. Topographic pattern recognition methods were applied and a normative database was established. Z-score statistics allowed identifying the number of subjects with significant abnormal values in each group. These values were compared with conventional single-channel waveform analysis. The diagnostic value of the new measures for MS reached a sensitivity of 72% and a specificity of 100% for the VEP, which was significantly higher than the conventional analysis. For the SEP, the specificity was also high (93%) but the sensitivity remained low as in the conventional analysis (30%). The quantitative topographic analysis of multichannel VEP revealed high-diagnostic sensitivity and specificity for MS. Moreover, the method reliably identified the most dominant VEP and SEP components in the healthy subject group. The results indicate that objective topographic analysis of multichannel recordings increase the value of VEP as surrogate marker for MS