Neuromagnetic Abnormality of Motor Cortical Activation and Phases of Headache Attacks in Childhood Migraine

The cerebral cortex serves a primary role in the pathogenesis of migraine. This aberrant brain activation in migraine can be noninvasively detected with magnetoencephalography (MEG). The objective of this study was to investigate the differences in motor cortical activation between attacks (ictal) and pain free intervals (interictal) in children and adolescents with migraine using both low- and high-frequency neuromagnetic signals. Thirty subjects with an acute migraine and 30 subjects with a history of migraine, while pain free, were compared to age- and gender-matched controls using MEG. Motor cortical activation was elicited by a standardized, validated finger-tapping task. Low-frequency brain activation (1∼50 Hz) was analyzed with waveform measurements and high-frequency oscillations (65–150 Hz) were analyzed with wavelet-based beamforming. MEG waveforms showed that the ictal latency of low-frequency brain activation was significantly delayed as compared with controls, while the interictal latency of brain activation was similar to that of controls. The ictal amplitude of low-frequency brain activation was significantly increased as compared with controls, while the interictal amplitude of brain activation was similar to that of controls. The ictal source power of high-frequency oscillations was significantly stronger than that of the controls, while the interictal source power of high-frequency oscillations was significantly weaker than that of controls. The results suggest that aberrant low-frequency brain activation in migraine during a headache attack returned to normal interictally. However, high-frequency oscillations changed from ictal hyper-activation to interictal hypo-activation. Noninvasive assessment of cortical abnormality in migraine with MEG opens a new window for developing novel therapeutic strategies for childhood migraine by maintaining a balanced cortical excitability.     

Altered Rolandic Gamma-Band Activation Associated with Motor Impairment and Ictal Network Desynchronization in Childhood Epilepsy

Epilepsy is associated with an abnormal expression of neural oscillations and their synchronization across brain regions. Oscillatory brain activation and synchronization also play an important role in cognition, perception and motor control. Childhood epilepsy is associated with a variety of cognitive and motor deficits, but the relationship between altered functional brain responses in various frequency ranges and functional impairment in these children remains poorly understood. We investigated functional magnetoencephalographic (MEG) responses from motor cortex in multiple functionally relevant frequency bands following median nerve stimulation in twelve children with epilepsy, including four children with motor impairments. We demonstrated that children with motor impairments exhibit an excessive gamma-band response from Rolandic cortex, and that the magnitude of this Rolandic gamma response is negatively associated with motor function. Abnormal responses from motor cortex were also associated with ictal desynchronization of oscillations within Rolandic cortex measured using intracranial EEG (iEEG). These results provide the evidence that ictal disruption of motor networks is associated with an altered functional response from motor cortex, which is in turn associated with motor impairment.     

Abnormal Movement Preparation in Task-Specific Focal Hand Dystonia

Electrophysiological and behavioral studies in primary dystonia suggest abnormalities during movement preparation, but this crucial phase preceding movement onset has not yet been studied specifically with functional magnetic resonance imaging (fMRI). To identify abnormalities in brain activation during movement preparation, we used event-related fMRI to analyze behaviorally unimpaired sequential finger movements in 18 patients with task-specific focal hand dystonia (FHD) and 18 healthy subjects. Patients and controls executed self-initiated or externally cued prelearnt four-digit sequential movements using either right or left hands. In FHD patients, motor performance of the sequential finger task was not associated with task-related dystonic posturing and their activation levels during motor execution were highly comparable with controls. On the other hand reduced activation was observed during movement preparation in the FHD patients in left premotor cortex / precentral gyrus for all conditions, and for self-initiation additionally in supplementary motor area, left mid-insula and anterior putamen, independent of effector side. Findings argue for abnormalities of early stages of motor control in FHD, manifesting during movement preparation. Since deficits map to regions involved in the coding of motor programs, we propose that task-specific dystonia is characterized by abnormalities during recruitment of motor programs: these do not manifest at the behavioral level during simple automated movements, however, errors in motor programs of complex movements established by extensive practice (a core feature of FHD), trigger the inappropriate movement patterns observed in task-specific dystonia.     

Ketamine-induced oscillations in the motor circuit of the rat basal ganglia

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion.We recorded local field potentials from motor cortex, caudate-putamen (CPU), substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN) in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg), and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting.Ketamine induced coherent oscillations in low gamma (~ 50 Hz), high gamma (~ 80 Hz) and high frequency (HFO, ~ 150 Hz) bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement.These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency-specific pattern of connectivity among the structures analyzed.     

Driving oscillatory activity in the human cortex enhances motor performance

Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements. In contrast, activity in the gamma (60-90 Hz) band increases during movement. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior.     

Motor Network Plasticity and Low-Frequency Oscillations Abnormalities in Patients with Brain Gliomas: A Functional MRI Study

Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC) and supplementary motor area (SMA). Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD) of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05). We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01–0.02 Hz; middle: 0.02–0.06 Hz; and high: 0.06–0.1 Hz), at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors.     

Primary Somatosensory Cortices Contain Altered Patterns of Regional Cerebral Blood Flow in the Interictal Phase of Migraine

The regulation of cerebral blood flow (CBF) is a complex integrated process that is critical for supporting healthy brain function. Studies have demonstrated a high incidence of alterations in CBF in patients suffering from migraine with and without aura during different phases of attacks. However, the CBF data collected interictally has failed to show any distinguishing features or clues as to the underlying pathophysiology of the disease. In this study we used the magnetic resonance imaging (MRI) technique—arterial spin labeling (ASL)—to non-invasively and quantitatively measure regional CBF (rCBF) in a case-controlled study of interictal migraine. We examined both the regional and global CBF differences between the groups, and found a significant increase in rCBF in the primary somatosensory cortex (S1) of migraine patients. The CBF values in S1 were positively correlated with the headache attack frequency, but were unrelated to the duration of illness or age of the patients. Additionally, 82% of patients reported skin hypersensitivity (cutaneous allodynia) during migraine, suggesting atypical processing of somatosensory stimuli. Our results demonstrate the presence of a disease-specific functional deficit in a known region of the trigemino-cortical pathway, which may be driven by adaptive or maladaptive functional plasticity. These findings may in part explain the altered sensory experiences reported between migraine attacks.     

Altered Hypothalamic Functional Connectivity with Autonomic Circuits and the Locus Coeruleus in Migraine

The hypothalamus has been implicated in migraine based on the manifestation of autonomic symptoms with the disease, as well as neuroimaging evidence of hypothalamic activation during attacks. Our objective was to determine functional connectivity (FC) changes between the hypothalamus and the rest of the brain in migraine patients vs. control subjects. This study uses fMRI (functional magnetic resonance imaging) to acquire resting state scans in 12 interictal migraine patients and 12 healthy matched controls. Hypothalamic connectivity seeds were anatomically defined based on high-resolution structural scans, and FC was assessed in the resting state scans. Migraine patients had increased hypothalamic FC with a number of brain regions involved in regulation of autonomic functions, including the locus coeruleus, caudate, parahippocampal gyrus, cerebellum, and the temporal pole. Stronger functional connections between the hypothalamus and brain areas that regulate sympathetic and parasympathetic functions may explain some of the hypothalamic-mediated autonomic symptoms that accompany or precede migraine attacks.     

Altered corticomuscular coherence elicited by paced isotonic contractions in individuals with cerebral palsy: A case-control study

The purpose of the study was to analyze corticomuscular coherence during planning and execution of simple hand movements in individuals with cerebral palsy (CP) and healthy controls (HC).Fourteen individuals with CP and 15 HC performed voluntary paced movements (opening and closing the fist) in response to a warning signal. Simultaneous scalp EEG and surface EMG of extensor carpi radialis brevis were recorded during 15 isotonic contractions. Time–frequency corticomuscular coherence (EMG-C3/C4) before and during muscular contraction, as well as EMG intensity, onset latency and duration were analyzed.Although EMG intensity was similar in both groups, individuals with CP exhibited longer onset latency and increased duration of the muscular contraction than HC. CP also showed higher corticomuscular coherence in beta EEG band during both planning and execution of muscular contraction, as well as lower corticomuscular coherence in gamma EEG band at the beginning of the contraction as compared with HC.In conclusion, our results suggest that individuals with CP are characterized by an altered functional coupling between primary motor cortex and effector muscles during planning and execution of isotonic contractions. In addition, the usefulness of corticomuscular coherence as a research tool for exploring deficits in motor central processing in persons with early brain damage is discussed.     

Cholinergic enhancement of visual attention and neural oscillations in the human brain

Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex.     

Temporal Lobe Cortical Thickness Correlations Differentiate the Migraine Brain from the Healthy Brain

BackgroundInterregional cortical thickness correlations reflect underlying brain structural connectivity and functional connectivity. A few prior studies have shown that migraine is associated with atypical cortical brain structure and atypical functional connectivity amongst cortical regions that participate in sensory processing. However, the specific brain regions that most accurately differentiate the migraine brain from the healthy brain have yet to be determined. The aim of this study was to identify the brain regions that comprised interregional cortical thickness correlations that most differed between migraineurs and healthy controls.MethodsThis was a cross-sectional brain magnetic resonance imaging (MRI) investigation of 64 adults with migraine and 39 healthy control subjects recruited from tertiary-care medical centers and their surrounding communities. All subjects underwent structural brain MRI imaging on a 3T scanner. Cortical thickness was determined for 70 brain regions that cover the cerebral cortex and cortical thickness correlations amongst these regions were calculated. Cortical thickness correlations that best differentiated groups of six migraineurs from controls and vice versa were identified.ResultsA model containing 15 interregional cortical thickness correlations differentiated groups of migraineurs from healthy controls with high accuracy. The right temporal pole was involved in 13 of the 15 interregional correlations while the right middle temporal cortex was involved in the other two.ConclusionsA model consisting of 15 interregional cortical thickness correlations accurately differentiates the brains of small groups of migraineurs from those of healthy controls. Correlations with the right temporal pole were highly represented in this classifier, suggesting that this region plays an important role in migraine pathophysiology.     

Human gamma oscillations during slow wave sleep

Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz) and high (60-120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.     

Physiological and pathological oscillatory networks in the human motor system.

Human brain functions are heavily contingent on neural interactions both at the single neuron and the neural population or system level. Accumulating evidence from neurophysiological studies strongly suggests that coupling of oscillatory neural activity provides an important mechanism to establish neural interactions. With the availability of whole-head magnetoencephalography (MEG) macroscopic oscillatory activity can be measured non-invasively from the human brain with high temporal and spatial resolution. To localise, quantify and map oscillatory activity and interactions onto individual brain anatomy we have developed the 'dynamic imaging of coherent sources' (DICS) method which allows to identify and analyse cerebral oscillatory networks from MEG recordings. Using this approach we have characterized physiological and pathological oscillatory networks in the human sensorimotor system. Coherent 8 Hz oscillations emerge from a cerebello-thalamo-premotor-motor cortical network and exert an 8 Hz oscillatory drive on the spinal motor neurons which can be observed as a physiological tremulousness of the movement termed movement discontinuities. This network represents the neurophysiological substrate of a discrete mode of motor control. In parkinsonian resting tremor we have identified an extensive cerebral network consisting of primary motor and lateral premotor cortex, supplementary motor cortex, thalamus/basal ganglia, posterior parietal cortex and secondary somatosensory cortex, which are entrained in the tremor or twice the tremor rhythm. This low frequency entrapment of motor areas likely plays an important role in the pathophysiology of parkinsonian motor symptoms. Finally, studies on patients with postural tremor in hepatic encephalopathy revealed that this type of tremor results from a pathologically slow thalamocortical and cortico-muscular coupling during isometric hold tasks. In conclusion, the analysis of oscillatory cerebral networks provides new insights into physiological mechanisms of motor control and pathophysiological mechanisms of tremor disorders.     

Intrinsic Brain Network Abnormalities in Migraines without Aura Revealed in Resting-State fMRI

Background

Previous studies have defined low-frequency, spatially consistent intrinsic connectivity networks (ICN) in resting functional magnetic resonance imaging (fMRI) data which reflect functional interactions among distinct brain areas. We sought to explore whether and how repeated migraine attacks influence intrinsic brain connectivity, as well as how activity in these networks correlates with clinical indicators of migraine.

Methods/Principal Findings

Resting-state fMRI data in twenty-three patients with migraines without aura (MwoA) and 23 age- and gender-matched healthy controls (HC) were analyzed using independent component analysis (ICA), in combination with a “dual-regression” technique to identify the group differences of three important pain-related networks [default mode network (DMN), bilateral central executive network (CEN), salience network (SN)] between the MwoA patients and HC. Compared with the HC, MwoA patients showed aberrant intrinsic connectivity within the bilateral CEN and SN, and greater connectivity between both the DMN and right CEN (rCEN) and the insula cortex - a critical region involving in pain processing. Furthermore, greater connectivity between both the DMN and rCEN and the insula correlated with duration of migraine.

Conclusions

Our findings may provide new insights into the characterization of migraine as a condition affecting brain activity in intrinsic connectivity networks. Moreover, the abnormalities may be the consequence of a persistent central neural system dysfunction, reflecting cumulative brain insults due to frequent ongoing migraine attacks.     

Localizing Movement-Related Primary Sensorimotor Cortices with Multi-Band EEG Frequency Changes and Functional MRI

Electroencephalographic (EEG) oscillations in multiple frequency bands can be observed during functional activity of the cerebral cortex. An important question is whether activity of focal areas of cortex, such as during finger movements, is tracked by focal oscillatory EEG changes. Although a number of studies have compared EEG changes to functional MRI hemodynamic responses, we can find no previous research that relates the fMRI hemodynamic activity to localization of the multiple EEG frequency changes observed in motor tasks. In the present study, five participants performed similar thumb and finger movement tasks in parallel EEG and functional MRI studies. We examined changes in five frequency bands (from 5–120 Hz) and localized them using 256 dense-array EEG (dEEG) recordings and high-resolution individual head models. These localizations were compared with fMRI localizations in the same participants. Results showed that beta-band (14–30 Hz) desynchronizations (power decreases) were the most robust effects, appearing in all individuals, consistently localized to the hand region of the primary motor cortex, and consistently aligned with fMRI localizations.     

Brain Function and Upper Limb Outcome in Stroke: A Cross-Sectional fMRI Study

Objective

The nature of changes in brain activation related to good recovery of arm function after stroke is still unclear. While the notion that this is a reflection of neuronal plasticity has gained much support, confounding by compensatory strategies cannot be ruled out. We address this issue by comparing brain activity in recovered patients 6 months after stroke with healthy controls.

Methods

We included 20 patients with upper limb paresis due to ischemic stroke and 15 controls. We measured brain activation during a finger flexion-extension task with functional MRI, and the relationship between brain activation and hand function. Patients exhibited various levels of recovery, but all were able to perform the task.

Results

Comparison between patients and controls with voxel-wise whole-brain analysis failed to reveal significant differences in brain activation. Equally, a region of interest analysis constrained to the motor network to optimize statistical power, failed to yield any differences. Finally, no significant relationship between brain activation and hand function was found in patients. Patients and controls performed scanner task equally well.

Conclusion

Brain activation and behavioral performance during finger flexion-extensions in (moderately) well recovered patients seems normal. The absence of significant differences in brain activity even in patients with a residual impairment may suggest that infarcts do not necessarily induce reorganization of motor function. While brain activity could be abnormal with higher task demands, this may also introduce performance confounds. It is thus still uncertain to what extent capacity for true neuronal repair after stroke exists.     

Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study

Background

Alternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities.

Methods

We used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used.

Results

One person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls.

Conclusions

We report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity.     

Sensorimotor and Pain Modulation Brain Abnormalities in Trigeminal Neuralgia: A Paroxysmal,Sensory-Triggered Neuropathic Pain

Objective

Idiopathic trigeminal neuralgia (TN) is characterized by paroxysms of severe facial pain but without the major sensory loss that commonly accompanies neuropathic pain. Since neurovascular compression of the trigeminal nerve root entry zone does not fully explain the pathogenesis of TN, we determined whether there were brain gray matter abnormalities in a cohort of idiopathic TN patients. We used structural MRI to test the hypothesis that TN is associated with altered gray matter (GM) in brain areas involved in the sensory and affective aspects of pain, pain modulation, and motor function. We further determined the contribution of long-term TN on GM plasticity.

Methods

Cortical thickness and subcortical GM volume were measured from high-resolution 3T T1-weighted MRI scans in 24 patients with right-sided TN and 24 healthy control participants.

Results

TN patients had increased GM volume in the sensory thalamus, amygdala, periaqueductal gray, and basal ganglia (putamen, caudate, nucleus accumbens) compared to healthy controls. The patients also had greater cortical thickness in the contralateral primary somatosensory cortex and frontal pole compared to controls. In contrast, patients had thinner cortex in the pregenual anterior cingulate cortex, the insula and the orbitofrontal cortex. No relationship was observed between GM abnormalities and TN pain duration.

Conclusions

TN is associated with GM abnormalities in areas involved in pain perception, pain modulation and motor function. These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain, and increased motor output to control facial movements to limit pain attacks.     

Human motor cortical activity is selectively phase-entrained on underlying rhythms

The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.     

Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response

PFAPA syndrome is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and/or cervical adenitis. It is of unknown etiology and manifests usually before 5 years of age. We determined serum and intracellular cytokine levels in six PFAPA patients (4 males, 2 females, mean age 8 years (+/- 1.2 SEM), range 4-13) during the symptom-free period as well as 6-12 hours and 18-24 hours after fever onset. Values were compared to age-matched, healthy controls. Febrile PFAPA attacks led to a significant increase in IL-6 and IFN-gamma serum concentrations compared to symptom-free periods and to controls, with IL-1beta, TNF-alpha and IL-12p70 levels being significantly higher than in controls. Lymphocytic IFN-gamma and CD8+ IL-2 production was consistently significantly elevated compared to healthy children. During the asymptomatic period, serum concentrations of IL-1beta, IL-6, TNF-alpha and IL-12p70 were significantly increased compared to controls. Intracellular TNF-alpha synthesis was not elevated at any time point. Soluble TNFRp55 levels were even lower in between febrile episodes, reaching values comparable to controls during attacks, whereas soluble TNFRp75 levels increased during attacks compared to healthy children. Anti-inflammatory IL-4 in serum was at all times lower in PFAPA patients compared to controls with no difference in levels of intracellular IL-4 and IL-10 or serum IL-10. The observed increase of pro-inflammatory mediators, even between febrile attacks, suggests a dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.