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Objective: Objective biomarkers for attention-deficit/hyperactivity disorder (ADHD) could improve diagnostics or treatment monitoring of this psychiatric disorder. The resting electroencephalogram (EEG) provides non-invasive spectral markers of brain function and development. Their accuracy as ADHD markers is increasingly questioned but may improve with pattern classification., Methods: This study provides an integrated analysis of ADHD and developmental effects in children and adults using regression analysis and support vector machine classification of spectral resting (eyes-closed) EEG biomarkers in order to clarify their diagnostic value., Results: ADHD effects on EEG strongly depend on age and frequency. We observed typical non-linear developmental decreases in delta and theta power for both ADHD and control groups. However, for ADHD adults we found a slowing in alpha frequency combined with a higher power in alpha-1 (8-10Hz) and beta (13-30Hz). Support vector machine classification of ADHD adults versus controls yielded a notable cross validated sensitivity of 67% and specificity of 83% using power and central frequency from all frequency bands. ADHD children were not classified convincingly with these markers., Conclusions: Resting state electrophysiology is altered in ADHD, and these electrophysiological impairments persist into adulthood., Significance: Spectral biomarkers may have both diagnostic and prognostic value., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Brain maturation in adolescence is mirrored by the EEG as a pronounced decrease in low frequency activity. This EEG power attenuation parallels reductions of structural and metabolic markers of neuronal maturation (i.e., gray matter loss and decrease of absolute cerebral glucose utilization). However, it is largely unknown what causes these electrophysiological changes, and how this functional reorganization relates to other functional measures such as the fMRI BOLD signal. In this study, we used simultaneously recorded EEG and fMRI to localize hemodynamic correlates of fluctuating EEG oscillations and to study the development of this EEG-BOLD coupling. Furthermore, the maturational EEG power attenuation was directly compared to BOLD signal power maturation. Both analyses were novel in their developmental perspective and aimed at providing a functional lead to EEG maturation. Data from 19 children, 18 adolescents and 18 young adults were acquired in 10 min eyes-open/eyes-closed resting states. Our results revealed that both EEG and BOLD amplitudes strongly decrease between childhood and adulthood, but their functional coupling remains largely unchanged. The global reduction of absolute amplitude of spontaneous slow BOLD signal fluctuation is a novel marker for brain maturation, and parallels the globally decreasing trajectories of EEG amplitudes, gray matter and glucose metabolism during adolescence. Further, the absence of thalamocortical EEG-BOLD coupling in children together with age-related normalized thalamic BOLD power increase indicated maturational changes in brain state regulation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that these opposite correlations with different distributions undergo similar and significant neuronal developments with brain maturation.

Chronic neuropathic pain may require a neurosurgical treatment, but for reasons that have not been fully explored yet, a significant number of patients do not benefit from the intervention. We compared the resting EEG of 15 healthy controls to the EEG of 23 chronic neuropathic pain patients before and 12 months after treatment by the central lateral thalamotomy (CLT). A patient subgroup had a high (n = 14, pain relief (PR)  ≥ 50%) and another subgroup a low (n = 9, PR < 50%) postoperative PR. EEG spectral power and source localization of the high PR patients were normalized postoperatively. In contrast, low PR patients showed postoperative maintenance of insular, cingulate and prefrontal overactivities, and their frustration values were positively correlated with cingulate and prefrontal activity. These findings demonstrate a normalizing effect of CLT on cortical activity and suggest that treatment resistance is associated with a frustration-based dynamics.

The transition from adolescence to adulthood is a critical stage in the human lifespan during which the brain still undergoes substantial structural and functional change. The changing frequency composition of the resting state EEG reflects maturation of brain function. This study investigated (post)adolescent brain maturation captured by two independently but simultaneously recorded neuronal signals: EEG and fMRI. Data were collected in a 20 min eyes-open/eyes-closed resting state paradigm. EEG, fMRI-BOLD signal and EEG-BOLD correlations were compared between groups of adults, age 25 (n=18), and adolescents, age 15 (n=18). A typical developmental decrease of low-frequency EEG power was observed even at this late stage of brain maturation. Frequency and condition specific EEG-fMRI correlations proved robust for multiple brain regions. However, no consistent change in the EEG-BOLD correlations was identified that would correspond to the neuronal maturation captured by the EEG. This result indicates that the EEG-BOLD correlation measures a distinct aspect of neurophysiological activity that presumably matures earlier, since it is less sensitive to late maturation than the neuronal activity captured by low-frequency EEG., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Greater low frequency power (<8 Hz) in the electroencephalogram (EEG) at rest is normal in the immature developing brain of children when compared to adults. Children with epilepsy also have greater low frequency interictal resting EEG activity. Whether these power elevations reflect brain immaturity due to a developmental lag or the underlying epileptic pathophysiology is unclear. The present study addresses this question by analyzing spectral EEG topographies and sources for normally developing children and children with epilepsy. We first compared the resting EEG of healthy children to that of healthy adults to isolate effects related to normal brain immaturity. Next, we compared the EEG from 10 children with generalized cryptogenic epilepsy to the EEG of 24 healthy children to isolate effects related to epilepsy. Spectral analysis revealed that global low (delta: 1-3 Hz, theta: 4-7 Hz), medium (alpha: 8-12 Hz) and high (beta: 13-25 Hz) frequency EEG activity was greater in children without epilepsy compared to adults, and even further elevated for children with epilepsy. Topographical and tomographic EEG analyses showed that normal immaturity corresponded to greater delta and theta activity at fronto-central scalp and brain regions, respectively. In contrast, the epilepsy-related activity elevations were predominantly in the alpha band at parieto-occipital electrodes and brain regions, respectively. We conclude that lower frequency activity can be a sign of normal brain immaturity or brain pathology depending on the specific topography and frequency of the oscillating neuronal network.

Background: EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown., Methodology: In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5-7 Hz), alpha1 (8-10), alpha2 (10-12 Hz), beta1 (13-20), beta2 (20-30 Hz), and gamma (30-40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects., Principal Findings: We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and--with one exception--beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects., Conclusions: We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.

Background: The physiopathological mechanism underlying the tinnitus phenomenon is still the subject of an ongoing debate. Since oscillatory EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions, this study investigates deviations from the norm of different resting EEG parameters in patients suffering from chronic tinnitus., Results: Spectral parameters of resting EEG of male tinnitus patients (n = 8, mean age 54 years) were compared to those of age-matched healthy males (n = 15, mean age 58.8 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz. Using LORETA source analysis, the generators of delta, theta, alpha and beta power increases were localized dominantly to left auditory (Brodmann Areas (BA) 41,42, 22), temporo-parietal, insular posterior, cingulate anterior and parahippocampal cortical areas., Conclusions: Tinnitus patients show a deviation from the norm of different resting EEG parameters, characterized by an overproduction of resting state delta, theta and beta brain activities, providing further support for the microphysiological and magnetoencephalographic evidence pointing to a thalamocortical dysrhythmic process at the source of tinnitus. These results also provide further confirmation that reciprocal involvements of both auditory and associative/paralimbic areas are essential in the generation of tinnitus.

Oscillatory and coherent EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions. We aimed to study deviations from the norm of different resting EEG parameters in Parkinson's disease (PD) patients. We compared spectral parameters of the resting EEG of PD patients (n=24, median age 67 years) to those of healthy controls (n=34, median age 62 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz, and the dominant peak was shifted towards lower frequencies. Maximal differences appeared in the 6-9 Hz theta band in all electrodes. Frontal electrodes contributed most to this difference in the 4-6 Hz theta, 12-18 Hz beta and 30-45 Hz gamma bands. On an individual basis, the combination of six spectral power band parameters discriminated between patient and control groups and 72% of all subjects were classified correctly. Using LORETA source analysis, the generators of this power difference were localized to fronto-insulo-temporal cortical areas in the theta and beta bands, and to interhemispheric frontal (supplementary motor area, SMA) and cingulate areas in the 30-45 Hz gamma band. We calculated spectral coherence between electrode pairs in a frontal, central and parietal region of interest (ROI). In the frontal ROI, coherence was enhanced significantly in the patient group in the theta, high beta and gamma bands. In the parietal ROI, patients showed lower coherence around 10 Hz. We demonstrate a deviation from the norm of different resting EEG parameters in PD patients. This evidence can be integrated in the context of a pathophysiological chain reaction initiated in the substantia nigra and resulting in a cortical aberrant dynamics rooted in enhanced dysrhythmic thalamocortical interactions.

In the literature on EEG during working memory (WM), the role of alpha power (8-13 Hz) during WM retention has remained unclear. We recorded EEG while 18 subjects retained sets of consonants in memory for 3 s; setsize (ss4, ss6, ss8) determines memory workload. Theta power (4-8 Hz) increased with workload in all subjects in middle frontal electrodes. Using ICA, the increase in theta could be attributed to one component whose generators were localized by sLORETA in the medial frontal gyrus. Alpha power in parietal electrode Pz showed a mean increase during retention as compared to prestimulus fixation (event-related synchronization, ERS). On an individual basis, alpha power increased with workload in 9 subjects (WL+ group) and decreased in 9 subjects (WL- group). The alpha increased in upper alpha for the WL+ group (mean: 10.4 Hz) and decreased in lower alpha for the WL- group (mean: 8.9 Hz). Time-frequency representations show high alpha power early during retention for the WL+ group and high alpha power late during retention for the WL- group. sLORETA revealed maximal contrast for the WL+ group in the cuneus and for the WL- group in the precuneus. In subjects with WL+, alpha increase in the cuneus may reflect WM maintenance or active inhibition of task-irrelevant areas. In subjects with WL-, alpha decrease in the precuneus may reflect release of inhibition associated with attentional demands. Thus, alpha EEG characterizes two aspects of processing in the same WM task.