Spontaneous Low-Frequency Cerebral Hemodynamics Oscillations in Restless Legs Syndrome with Periodic Limb Movements During Sleep: A Near-Infrared Spectroscopy Study.

BACKGROUND AND PURPOSE: Periodic limb movements (PLM) during sleep (PLMS) are associated with cortical and cardiovascular activation. Changes in cerebral hemodynamics caused by cortical activity can be measured using near-infrared spectroscopy (NIRS). We investigated oscillatory components of cerebral hemodynamics during PLM and different sleep stages in restless legs syndrome (RLS) patients with PLMS. METHODS: Four female RLS patients with PLMS, and four age- and sex-matched normal controls were included. PLM and sleep stages were scored using polysomnography, while the spontaneous cerebral hemodynamics was measured by NIRS. The phase and amplitude of the cerebral oxyhemoglobin concentration [HbO] and the deoxyhemoglobin concentration [Hb] low-frequency oscillations (LFOs) were evaluated during each sleep stage [waking, light sleep (LS; stages N1 and N2), slow-wave sleep (stage N3), and rapid eye movement (REM) sleep]. In RLS patients with PLMS, the cerebral hemodynamics during LS was divided into LS with and without PLM. RESULTS: The cerebral hemodynamics activity varied among the different sleep stages. There were changes in phase differences between [HbO] and [Hb] LFOs during the different sleep stages in the normal controls but not in the RLS patients with PLMS. The [HbO] and [Hb] LFO amplitudes were higher in the patient group than in controls during both LS with PLM and REM sleep. CONCLUSIONS: The present study has demonstrated the presence of cerebral hemodynamics disturbances in RLS patients with PLMS, which may contribute to an increased risk of cerebrovascular events.

Regional and inter-regional theta oscillation during episodic novelty processing.

Recent event-related potential (ERP) and functional magnetic resonance imaging (fMRI) studies suggest that novelty processing may be involved in processes that recognize the meaning of a novel sound, during which widespread cortical regions including the right prefrontal cortex are engaged. However, it remains unclear how those cortical regions are functionally integrated during novelty processing. Because theta oscillation has been assumed to have a crucial role in memory operations, we examined local and inter-regional neural synchrony of theta band activity during novelty processing. Fifteen right-handed healthy university students participated in this study. Subjects performed an auditory novelty oddball task that consisted of the random sequence of three types of stimuli such as a target (1000Hz pure tone), novel (familiar environmental sounds such as dog bark, buzz, car crashing sound and so on), and standard sounds (950Hz pure tone). Event-related spectra perturbation (ERSP) and the phase-locking value (PLV) were measured from human scalp EEG during task. Non-parametric statistical tests were applied to test for significant differences between stimulus novelty and stimulus targets in ERSP and PLV. The novelty P3 showed significant higher amplitude and shorter latency compared with target P3 in frontocentral regions. Overall, theta activity was significantly higher in the novel stimuli compared with the target stimuli. Specifically, the difference in theta power between novel and target stimuli was most significant in the right frontal region. This right frontal theta activity was accompanied by phase synchronization with the left temporal region. Our results imply that theta phase synchronization between right frontal and left temporal regions underlie the retrieval of memory traces for unexpected but familiar sounds from long term memory in addition to working memory retrieval or novelty encoding.

Topography of sensory symptoms in patients with drug-naïve restless legs syndrome.

OBJECTIVES: We aimed to describe the sensory topography of restless legs syndrome (RLS) sensory symptoms and to identify the relationship between topography and clinical variables. METHODS: Eighty adult patients with drug-naïve RLS who had symptoms for more than 1year were consecutively recruited. During face-to-face interviews using a structured paper and pencil questionnaire with all participants, we obtained clinical information and also marked the topography of RLS sensory symptoms on a specified body template, all of which were subsequently inputted into our in-house software. The RLS sensory topography patterns were classified according to localization, lateralization, and symmetry. We investigated if these sensory topography patterns differed according to various clinical variables. RESULTS: The lower extremities only (LE) were the most common location (72.5%), and 76.3% of participants exhibited symmetric sensory topography. Late-onset RLS showed more asymmetric sensory distribution compared with early-onset RLS (P=.024). Patients whose sensory symptoms involved the lower extremities in addition to other body parts (LE-PLUS) showed more severe RLS compared with those involving the LE (P=.037). CONCLUSION: RLS sensory symptoms typically were symmetrically located in the lower extremities. LE-PLUS or an asymmetric distribution more often occurred in patients with more severe RLS symptoms or late-onset RLS.

Fronto-temporal interactions in the theta-band during auditory deviant processing.

Mismatch negativity (MMN) is a negative component of event-related potential (ERP) that reflects auditory deviant detection. Previous studies repeatedly suggested that MMN is generated by the fronto-temporal network. However, it is still unclear how the frontal and temporal areas interact. To verify this, we observed the spatiotemporal pattern of inter-regional functional connectivity using phase synchrony and Granger causality, by analyzing event-related electroencephalograms (EEGs) elicited by standard and deviant tones in an oddball paradigm. Strong theta-band phase synchrony and bidirectional Granger causality were observed between the frontal and temporal areas during the processing of auditory deviants, especially at the temporal interval of MMN. Our results support the hypothesis that fronto-temporal interactions are crucial to the generation of MMN during auditory deviant processing.

Reduced Frontal P3a Amplitude in Migraine Patients during the Pain-Free Period.

BACKGROUND AND PURPOSE: Neuropsychological and neuroimaging studies both suggest that frontal lobe dysfunction is present in migraineurs. Since P3a abnormalities manifest in other diseases associated with attention problems, such as attention deficit hyperactivity disorder, we hypothesized that migraine patients have P3a abnormalities, particularly in the frontal region. METHODS: Event-related potentials were measured using a passive auditory oddball paradigm in 16 female migraineurs (aged 22.9±2.0 years, mean±SD) during the interictal period and in 16 age-matched healthy females (22.6±2.0 years). The amplitudes and latencies were analyzed independently using repeated-measures analysis of variance. Nonparametric statistical testing using a cluster-level randomization method was performed to localize the abnormalities. RESULTS: The mean P3a amplitude at frontal areas during the third trials was significantly lower in migraineurs (1.06 µV) than in controls (1.69 µV, p=0.026). P3a amplitudes were negatively correlated with the duration of the migraine history (r=-0.618, p=0.014). Cluster-based nonparametric statistical analysis showed that the amplitudes over left frontal areas were significantly lower in migraine patients than in controls. CONCLUSIONS: A reduced P3a amplitude of migraineurs reflects attentional deficits and frontal dysfunction. The negative correlation between P3a amplitude and the duration of the migraine history suggests that attentional deficits and frontal dysfunction are either the cause or the result of headache.

Reduced neural synchrony in patients with restless legs syndrome during a visual oddball task.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an irresistible urge to move the legs. It has been reported that RLS patients show cognitive deficits, presumably due to hyperactivity causing loss of attention, or malfunctions in the frontal region resulting from sleep deprivation. However, the mechanism underlying cognitive deficits in RLS patients is mostly unknown. As an effort to clarifying this, we investigated the differences in neural activity and phase synchrony between healthy controls and RLS patients during cognitive task performances. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen female drug-naive RLS patients were enrolled in the study, and an age-matched group of thirteen healthy female volunteers served as controls. Multichannel event-related potentials (ERPs) were recorded from RLS patients and normal controls while performing a visual oddball task. In addition to conventional analyses of ERP waveforms and spectra, interregional gamma-band phase synchrony (GBPS) was investigated to observe the differences in interregional neural synchronies between normal and RLS patient groups. Strong GBPS was observed primarily between anterior and posterior regions along the midline for both groups. Along with significant reduction and delay of P300 ERP and induced gamma-band activity (GBA), the GBPS was considerably decreased in RLS patients compared to normal subjects, especially at frontal region. CONCLUSIONS: Overall, our results support that cognitive dysfunction in RLS patients is associated with reduced interregional neural synchrony as well as alterations in local neural activity.

Theta oscillation related to the auditory discrimination process in mismatch negativity: oddball versus control paradigm.

BACKGROUND AND PURPOSE: The aim of this study was to identify the mechanism underlying the auditory discriminatory process reflected in mismatch negativity (MMN), using time-frequency analysis of single-trial event-related potentials (ERPs). METHODS: Two auditory tones of different probabilities (oddball paradigm) and the same probability (control paradigm) were used. The average dynamic changes in amplitude were evaluated, and the in-phase consistency of the EEG spectrum at each frequency and time window across trials, event-related spectral perturbations (ERSPs), and inter-trial phase coherence (ITC) were computed. RESULTS: Subtraction of the ERPs of standard stimuli from the ERPs of deviant stimuli revealed a clear MMN component in the oddball paradigm. However, no discernible MMN component was observed in the control paradigm. Statistical tests showed that in the oddball paradigm, deviant tones produced significant increases of theta ERSPs and ITC at around 250 ms as compared with the standard tone, while no significant difference between the two stimuli was observed in the control paradigm. CONCLUSIONS: Our results confirm that the auditory discriminatory process reflected in MMN is accompanied by phase resetting and power modulation at the theta frequency.

Electrophysiologic disturbances during daytime in patients with restless legs syndrome: further evidence of cognitive dysfunction?

BACKGROUNDS: It has been reported that patients with restless legs syndrome (RLS) may have cognitive deficit. The authors performed EEG and ERP analysis during daytime to identify electrophysiologic relations with cognitive dysfunction in unmedicated RLS patients. METHODS: Seventeen drug naive RLS patients (53.7±9.6 years) and 13 age-matched healthy controls participated in the present study. EEG was recorded during the waking-resting state and during a visual oddball task. RLS severities were determined using the International RLS Severity Scale. Stanford sleepiness scale (SSS) and bothersomeness visual analog scale (VAS) scores were determined immediately after ERP sessions. EEG power spectra and P300 amplitude and latency were compared for patients and controls. Clinical variables were correlated with P300 findings. RESULTS: Waking-resting EEG showed that RLS patients had significantly higher beta activity in frontocentral regions than controls. SSS scores were not different in the two groups. But the bothersomeness VAS scores of RLS patients were significantly higher than those of controls. Furthermore, P300 latency was significantly longer in patients, and patients had significantly lower P300 amplitudes in frontal and central locations. In addition, P300 latency was found to be significantly correlated with bothersomeness during the ERP test, whereas P300 amplitude showed no such tendency. CONCLUSIONS: Our study supports the notion that RLS patients have an underlying cognitive dysfunction. Significant correlations found between P300 latency and bothersomeness, a lack of sleepiness during the ERP test, and increased beta activity in resting state EEGs suggest that a combination of inattention and cortical dysfunction underlie cognitive dysfunction in RLS.