Increased Delta Power Research Articles

Impact of sleep loss before learning on cortical dynamics during memory retrieval

Evidence shows that sleep loss before learning decreases activation of the hippocampus during encoding and promotes forgetting. But it remains to be determined which neural systems are functionally affected during memory retrieval after one night of recovery sleep. To investigate this issue, we evaluated memory for pairs of famous people's faces with the same or different profession (i.e., semantically congruent or incongruent faces) after one night of undisturbed sleep in subjects who either underwent 4hours of acute sleep restriction (ASR, N=20) or who slept 8hours the pre-training night (controls, N=20). EEG recordings were collected during the recognition memory task in both groups, and the cortical sources generating this activity localized by applying a spatial beamforming filter in the frequency domain. Even though sleep restriction did not affect accuracy of memory performance, controls showed a much larger decrease of alpha power relative to a baseline period when compared to sleep-deprived subjects. These group differences affected a widespread frontotemporoparietal network involved in retrieval of episodic/semantic memories. Regression analyses further revealed that associative memory in the ASR group was negatively correlated with alpha power in the occipital regions, whereas the benefit of congruency in the same group was positively correlated with delta power in the left lateral prefrontal cortex. Retrieval-related decreases of alpha power have been associated with the reactivation of material-specific memory representations, whereas increases of delta power have been related to inhibition of interferences that may affect the performance of the task. We can therefore draw the conclusion that a few hours of sleep loss in the pre-training night, though insufficient to change the memory performance, is sufficient to alter the processes involved in retrieving and manipulating episodic and semantic information.

Low-frequency stimulation of the external globus palladium produces anti-epileptogenic and anti-ictogenic actions in rats.

To investigate the anti-epileptic effects of deep brain stimulation targeting the external globus palladium (GPe) in rats. For inducing amygdala kindling and deep brain stimulation, bipolar stainless-steel electrodes were implanted in SD rats into right basolateral amygdala and right GPe, respectively. The effects of deep brain stimulation were evaluated in the amygdala kindling model, maximal electroshock model (MES) and pentylenetetrazole (PTZ) model. Moreover, the background EEGs in the amygdala and GPe were recorded. Low-frequency stimulation (0.1 ms, 1 Hz, 15 min) at the GPe slowed the progression of seizure stages and shortened the after-discharge duration (ADD) during kindling acquisition. Furthermore, low-frequency stimulation significantly decreased the incidence of generalized seizures, suppressed the average stage, and shortened the cumulative ADD and generalized seizure duration in fully kindled rats. In addition, low-frequency stimulation significantly suppressed the average stage of MES-induced seizures and increased the latency to generalized seizures in the PTZ model. High-frequency stimulation (0.1 ms, 130 Hz, 5 min) at the GPe had no anti-epileptic effect and even aggravated epileptogenesis induced by amygdala kindling. EEG analysis showed that low-frequency stimulation at the GPe reversed the increase in delta power, whereas high-frequency stimulation at the GPe had no such effect. Low-frequency stimulation, but not high-frequency stimulation, at the GPe exerts therapeutic effect on temporal lobe epilepsy and tonic-colonic generalized seizures, which may be due to interference with delta rhythms. The results suggest that modulation of GPe activity using low-frequency stimulation or drugs may be a promising epilepsy treatment.

EEG Spectral Features Discriminate between Alzheimer's and Vascular Dementia.

Alzheimer’s disease (AD) and vascular dementia (VaD) present with similar clinical symptoms of cognitive decline, but the underlying pathophysiological mechanisms differ. To determine whether clinical electroencephalography (EEG) can provide information relevant to discriminate between these diagnoses, we used quantitative EEG analysis to compare the spectra between non-medicated patients with AD (n = 77) and VaD (n = 77) and healthy elderly normal controls (NC) (n = 77). We use curve-fitting with a combination of a power loss and Gaussian function to model the averaged resting-state spectra of each EEG channel extracting six parameters. We assessed the performance of our model and tested the extracted parameters for group differentiation. We performed regression analysis in a multivariate analysis of covariance with group, age, gender, and number of epochs as predictors and further explored the topographical group differences with pair-wise contrasts. Significant topographical differences between the groups were found in several of the extracted features. Both AD and VaD groups showed increased delta power when compared to NC, whereas the AD patients showed a decrease in alpha power for occipital and temporal regions when compared with NC. The VaD patients had higher alpha power than NC and AD. The AD and VaD groups showed slowing of the alpha rhythm. Variability of the alpha frequency was wider for both AD and VaD groups. There was a general decrease in beta power for both AD and VaD. The proposed model is useful to parameterize spectra, which allowed extracting relevant clinical EEG key features that move toward simple and interpretable diagnostic criteria.

Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression.

Major depressive disorder (MDD) is a serious public health burden and a leading cause of disability. Its pharmacotherapy is currently limited to modulators of monoamine neurotransmitters and second-generation antipsychotics. Recently, glutamatergic approaches for the treatment of MDD have increasingly received attention, and preclinical research suggests that metabotropic glutamate receptor 5 (mGlu5) inhibitors have antidepressant-like properties. Basimglurant (2-chloro-4-[1-(4-fluoro-phenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]-pyridine) is a novel mGlu5 negative allosteric modulator currently in phase 2 clinical development for MDD and fragile X syndrome. Here, the comprehensive preclinical pharmacological profile of basimglurant is presented with a focus on its therapeutic potential for MDD and drug-like properties. Basimglurant is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties that are corroborated by its functional magnetic imaging profile as well as anxiolytic-like and antinociceptive features. In electroencephalography recordings, basimglurant shows wake-promoting effects followed by increased delta power during subsequent non-rapid eye movement sleep. In microdialysis studies, basimglurant had no effect on monoamine transmitter levels in the frontal cortex or nucleus accumbens except for a moderate increase of accumbal dopamine, which is in line with its lack of pharmacological activity on monoamine reuptake transporters. These data taken together, basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features that suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy.

Oscillatory correlates of autobiographical memory

Recollection of events from one's own life is referred to as autobiographical memory. Autobiographical memory is an important part of our self. Neuroimaging findings link self-referential processes with the default mode network (DMN). Much evidence coming primarily from functional magnetic resonance imaging studies shows that autobiographical memory and DMN have a common neural base. In this study, electroencephalographic data collected in 47 participants during recollection of autobiographical episodes were analyzed using temporal and spatial independent component analyses in combination with source localization. Autobiographical remembering was associated with an increase of spectral power in alpha and beta and a decrease in delta band. The increase of alpha power, as estimated by sLORETA, was most prominent in the posterior DMN, but was also observed in visual and motor cortices, prompting an assumption that it is associated with activation of DMN and inhibition of irrelevant sensory and motor areas. In line with data linking delta oscillations with aversive states, decrease of delta power was more pronounced in episodes associated with positive emotions, whereas episodes associated with negative emotions were accompanied by an increase of delta power. Vividness of recollection correlated positively with theta oscillations. These results highlight the leading role of alpha oscillations and the DMN in the processes accompanying autobiographical remembering.

Modification of EEG functional connectivity and EEG power spectra in overweight and obese patients with food addiction: An eLORETA study.

We evaluated the modifications of electroencephalographic (EEG) power spectra and EEG connectivity in overweight and obese patients with elevated food addiction (FA) symptoms. Fourteen overweight and obese patients (3 men and 11 women) with three or more FA symptoms and fourteen overweight and obese patients (3 men and 11 women) with two or less FA symptoms were included in the study. EEG was recorded during three different conditions: 1) five minutes resting state (RS), 2) five minutes resting state after a single taste of a chocolate milkshake (ML-RS), and 3) five minutes resting state after a single taste of control neutral solution (N-RS). EEG analyses were conducted by means of the exact Low Resolution Electric Tomography software (eLORETA). Significant modification was observed only in the ML-RS condition. Compared to controls, patients with three or more FA symptoms showed an increase of delta power in the right middle frontal gyrus (Brodmann Area [BA] 8) and in the right precentral gyrus (BA 9), and theta power in the right insula (BA 13) and in the right inferior frontal gyrus (BA 47). Furthermore, compared to controls, patients with three or more FA symptoms showed an increase of functional connectivity in fronto-parietal areas in both the theta and alpha band. The increase of functional connectivity was also positively associated with the number of FA symptoms. Taken together, our results show that FA has similar neurophysiological correlates of other forms of substance-related and addictive disorders suggestingsimilar psychopathological mechanisms.

Chaos analysis of EEG during isoflurane-induced loss of righting in rats.

It has long been known that electroencephalogram (EEG) signals generate chaotic strange attractors and the shape of these attractors correlate with depth of anesthesia. We applied chaos analysis to frontal cortical and hippocampal micro-EEG signals from implanted microelectrodes (layer 4 and CA1, respectively). Rats were taken to and from loss of righting reflex (LORR) with isoflurane and behavioral measures were compared to attractor shape. Resting EEG signals at LORR differed markedly from awake signals, more similar to slow wave sleep signals, and easily discerned in raw recordings (high amplitude slow waves), and in fast Fourier transform analysis (FFT; increased delta power), in good agreement with previous studies. EEG activation stimulated by turning rats on their side, to test righting, produced signals quite similar to awake resting state EEG signals. That is, the high amplitude slow wave activity changed to low amplitude fast activity that lasted for several seconds, before returning to slow wave activity. This occurred regardless of whether the rat was able to right itself, or not. Testing paw pinch and tail clamp responses produced similar EEG activations, even from deep anesthesia when burst suppression dominated the spontaneous EEG. Chaotic attractor shape was far better at discerning between these awake-like signals, at loss of responses, than was FFT analysis. Comparisons are provided between FFT and chaos analysis of EEG during awake walking, slow wave sleep, and isoflurane-induced effects at several depths of anesthesia. Attractors readily discriminated between natural sleep and isoflurane-induced “delta” activity. Chaotic attractor shapes changed gradually through the transition from awake to LORR, indicating that this was not an on/off like transition, but rather a point along a continuum of brain states.

Sleep fragmentation has differential effects on obese and lean mice.

Chronic sleep fragmentation (SF), common in patients with sleep apnea, correlates with the development of obesity. We hypothesized that SF differentially affects neurobehavior in lean wild-type (WT) and obese pan-leptin receptor knockout (POKO) mice fed the same normal diet. First, we established an SF paradigm by interrupting sleep every 2min during the inactive light span. The maneuver was effective in decreasing sleep duration and bout length, and in increasing sleep state transition and waking, without significant rebound sleep in the dark span. Changes of sleep architecture were evident in the light span and consistent across days 1-10 of SF. There was reduced NREM, shortened sleep latency, and increased state transitions. During the light span of the first day of SF, there also was reduction of REM and increased delta power of slow-wave sleep. Potential effects of SF on thermal pain threshold, locomotor activity, and anxiety were then tested. POKO mice had a lower circadian amplitude of pain latency than WT mice in the hot plate test, and both groups had lowest tolerance at 4pm (zeitgeber time (ZT) 10) and longest latency at 4am (ZT 22). SF increased the pain threshold in WT but not in POKO mice when tested at 8a.m. (ZT 2). Both the POKO mutation and SF resulted in reduced physical activity and increased anxiety, but there was no additive effect of these two factors. Overall, SF and the POKO mutation differentially regulate mouse behavior. The results suggest that obesity can blunt neurobehavioral responses to SF.

Modification of EEG power spectra and EEG connectivity in autobiographical memory: a sLORETA study

The aim of the present study was to explore the modifications of scalp EEG power spectra and EEG connectivity during the autobiographical memory test (AM-T) and during the retrieval of an autobiographical event (the high school final examination, Task 2). Seventeen healthy volunteers were enrolled (9 women and 8 men, mean age 23.4 ± 2.8 years, range 19-30). EEG was recorded at baseline and while performing the autobiographical memory (AM) tasks, by means of 19 surface electrodes and a nasopharyngeal electrode. EEG analysis was conducted by means of the standardized LOw Resolution Electric Tomography (sLORETA) software. Power spectra and lagged EEG coherence were compared between EEG acquired during the memory tasks and baseline recording. The frequency bands considered were as follows: delta (0.5-4 Hz); theta (4.5-7.5 Hz); alpha (8-12.5 Hz); beta1 (13-17.5 Hz); beta2 (18-30 Hz); gamma (30.5-60 Hz). During AM-T, we observed a significant delta power increase in left frontal and midline cortices (T = 3.554; p < 0.05) and increased EEG connectivity in delta band in prefrontal, temporal, parietal, and occipital areas, and for gamma bands in the left temporo-parietal regions (T = 4.154; p < 0.05). In Task 2, we measured an increased power in the gamma band located in the left posterior midline areas (T = 3.960; p < 0.05) and a significant increase in delta band connectivity in the prefrontal, temporal, parietal, and occipital areas, and in the gamma band involving right temporo-parietal areas (T = 4.579; p < 0.05). These results indicate that AM retrieval engages in a complex network which is mediated by both low- (delta) and high-frequency (gamma) EEG bands.

The Contribution of EEG to the Diagnosis of Dementia

Changes induced by cerebrovascular damage (CVD) and amigdalo-hippocampal atrophy (AHC) on brain rhythmicity as revealed by scalp electroencephalography (EEG) were evaluated in a cohort of subjects with mild cognitive impairment (MCI) in order to detect different EEG patterns due to the vascular or degenerative impairment. All subjects underwent EEG recording and magnetic resonance imaging (MRI). EEGs were recorded at rest. Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha 3 frequency bands. Increased delta power and decreased alpha2 power were associated with the load of cerebrovascular damage (CVD). Moreover, the theta/alpha 1 ratio could be a reliable index for the estimation of the individual extent of CV damage. No association of vascular damage was observed with alpha3 power. On the other side, moderate hippocampal atrophy was related to an increase of alpha2 and alpha3 frequency power ratio. Our results show that different EEG markers are associated to vascular dementia and Alzheimer’s disease (AD). EEG markers could be expression of different global network pathological changes, helping in differentiation of prodromal AD from vascular demented patients. MCI stated that EEG markers could have a prospective value in differential diagnosis between vascular and degenerative MCI.

Behavioral and biochemical dissociation of arousal and homeostatic sleep need influenced by prior wakeful experience in mice

Sleep is regulated by homeostatic mechanisms, and the low-frequency power in the electroencephalogram (delta power) during non-rapid eye movement sleep reflects homeostatic sleep need. Additionally, sleep is limited by circadian and environmentally influenced arousal. Little is known, however, about the underlying neural substrates for sleep homeostasis and arousal and about the potential link between them. Here, we subjected C57BL/6 mice to 6 h of sleep deprivation using two different methods: gentle handling and continual cage change. Both groups were deprived of sleep to a similar extent (>99%), and, as expected, the delta power increase during recovery sleep was quantitatively similar in both groups. However, in a multiple sleep latency test, the cage change group showed significantly longer sleep latencies than the gentle handling group, indicating that the cage change group had a higher level of arousal despite the similar sleep loss. To investigate the possible biochemical correlates of these behavioral changes, we screened for arousal-related and sleep need-related phosphoprotein markers from the diencephalon. We found that the abundance of highly phosphorylated forms of dynamin 1, a presynaptic neuronal protein, was associated with sleep latency in the multiple sleep latency test. In contrast, the abundance of highly phosphorylated forms of N-myc downstream regulated gene 2, a glial protein, was increased in parallel with delta power. The changes of these protein species disappeared after 2 h of recovery sleep. These results suggest that homeostatic sleep need and arousal can be dissociated behaviorally and biochemically and that phosphorylated N-myc downstream regulated gene 2 and dynamin 1 may serve as markers of homeostatic sleep need and arousal, respectively.

Glutamatergic Signaling from the Parabrachial Nucleus Plays a Critical Role in Hypercapnic Arousal

The mechanisms of arousal from apneas during sleep in patients suffering from obstructive sleep apnea are not well understood. However, we know that respiratory chemosensory pathways converge on the parabrachial nucleus (PB), which sends glutamatergic projections to a variety of forebrain structures critical to arousal, including the basal forebrain, lateral hypothalamus, midline thalamus, and cerebral cortex. We tested the role of glutamatergic signaling in this pathway by developing an animal model for repetitive CO2 arousals (RCAs) and investigating the effect of deleting the gene for the vesicular glutamate transporter 2 (Vglut2) from neurons in the PB. We used mice with lox P sequences flanking exon2 of the Vglut2 gene, in which adeno-associated viral vectors containing genes encoding Cre recombinase and green fluorescent protein were microinjected into the PB to permanently and selectively disrupt Vglut2 expression while labeling the affected neurons. We recorded sleep in these mice and then investigated the arousals during RCA. Vglut2 deletions that included the external lateral and lateral crescent subdivisions of the lateral PB more than doubled the latency to arousal and resulted in failure to arouse by 30 s in >30% of trials. By contrast, deletions that involved the medial PB subdivision had minimal effects on arousal during hypercapnia but instead increased non-rapid eye movement (NREM) sleep by ∼43% during the dark period, and increased delta power in the EEG during NREM sleep by ∼50%. Our results suggest that glutamatergic neurons in the lateral PB are necessary for arousals from sleep in response to CO2, while medial PB glutamatergic neurons play an important role in promoting spontaneous waking.

Homeostatic and Circadian Contribution to EEG and Molecular State Variables of Sleep Regulation

Besides their well-established role in circadian rhythms, our findings that the forebrain expression of the clock-genes Per2 and Dbp increases and decreases, respectively, in relation to time spent awake suggest they also play a role in the homeostatic aspect of sleep regulation. Here, we determined whether time of day modulates the effects of elevated sleep pressure on clock-gene expression. Time of day effects were assessed also for recognized electrophysiological (EEG delta power) and molecular (Homer1a) markers of sleep homeostasis. EEG and qPCR data were obtained for baseline and recovery from 6-h sleep deprivation starting at ZT0, -6, -12, or -18. Mouse sleep laboratory. Male mice. Sleep deprivation. The sleep-deprivation induced changes in Per2 and Dbp expression importantly varied with time of day, such that Per2 could even decrease during sleep deprivations occurring at the decreasing phase in baseline. Dbp showed similar, albeit opposite dynamics. These unexpected results could be reliably predicted assuming that these transcripts behave according to a driven damped harmonic oscillator. As expected, the sleep-wake distribution accounted for a large degree of the changes in EEG delta power and Homer1a. Nevertheless, the sleep deprivation-induced increase in delta power varied also with time of day with higher than expected levels when recovery sleep started at dark onset. Per2 and delta power are widely used as exclusive state variables of the circadian and homeostatic process, respectively. Our findings demonstrate a considerable cross-talk between these two processes. As Per2 in the brain responds to both sleep loss and time of day, this molecule is well positioned to keep track of and to anticipate homeostatic sleep need. Curie T; Mongrain V; Dorsaz S; Mang GM; Emmenegger Y; Franken P. Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation. SLEEP 2013;36(3):311-323.

The functional significance of delta oscillations in cognitive processing

Ample evidence suggests that electroencephalographic (EEG) oscillatory activity is linked to a broad variety of perceptual, sensorimotor, and cognitive operations. However, few studies have investigated the delta band (0.5–3.5 Hz) during different cognitive processes. The aim of this review is to present data and propose the hypothesis that sustained delta oscillations inhibit interferences that may affect the performance of mental tasks, possibly by modulating the activity of those networks that should be inactive to accomplish the task. It is clear that two functionally distinct and potentially competing brain networks can be broadly distinguished by their contrasting roles in attention to the external world vs. the internally directed mentation or concentration. During concentration, EEG delta (1–3.5 Hz) activity increases mainly in frontal leads in different tasks: mental calculation, semantic tasks, and the Sternberg paradigm. This last task is considered a working memory task, but in neural, as well as phenomenological, terms, working memory can be best understood as attention focused on an internal representation. In the Sternberg task, increases in power in the frequencies from 1 to 3.90 Hz in frontal regions are reported. In a Go/No-Go task, power increases at 1 Hz in both conditions were observed during 100–300 ms in central, parietal and temporal regions. However, in the No-Go condition, power increases were also observed in frontal regions, suggesting its participation in the inhibition of the motor response. Increases in delta power were also reported during semantic tasks in children. In conclusion, the results suggest that power increases of delta frequencies during mental tasks are associated with functional cortical deafferentation, or inhibition of the sensory afferences that interfere with internal concentration. These inhibitory oscillations would modulate the activity of those networks that should be inactive to accomplish the task.

Modifications of EEG power spectra in mesial temporal lobe during n-back tasks of increasing difficulty. A sLORETA study

The n-back task is widely used to investigate the neural basis of Working Memory (WM) processes. The principal aim of this study was to explore and compare the EEG power spectra during two n-back tests with different levels of difficulty (1-back vs. 3-back). Fourteen healthy subjects were enrolled (seven men and seven women, mean age 31.21 ± 7.05 years, range: 23–48). EEG was recorded while performing the N-back test, by means of 19 surface electrodes referred to joint mastoids. EEG analysis were conducted by means of the standardized Low Resolution brain Electric Tomography (sLORETA) software. The statistical comparison between EEG power spectra in the two conditions was performed using paired t-statistics on the coherence values after Fisher's z transformation available in the LORETA program package. The frequency bands considered were: delta (0.5–4 Hz); theta (4.5–7.5 Hz); alpha (8–12.5 Hz); beta (13–30 Hz); gamma (30.5–100 Hz). Significant changes occurred in the delta band: in the 3-back condition an increased delta power was localized in a brain region corresponding to the Brodmann Area (BA) 28 in the left posterior entorhinal cortex (T = 3.112; p < 0.05) and in the BA 35 in the left perirhinal cortex in the parahippocampal gyrus (T = 2.876; p < 0.05). No significant differences were observed in the right hemisphere and in the alpha, theta, beta, and gamma frequency bands. Our results indicate that the most prominent modification induced by the increased complexity of the task occur in the mesial left temporal lobe structures.

Resting state in Alzheimer's disease: a concurrent analysis of Flash-Visual Evoked Potentials and quantitative EEG

BackgroundTo investigate to what extent Alzheimer's Disease (AD) affects Resting State activity, the possible impairment of independent electrophysiological parameters was determined in Eye-open and Eye-closed Conditions. Specifically, Flash-Visual Evoked Potential (F-VEP) and quantitative EEG (q-EEG) were examined to establish whether abnormalities of the former were systematically associated with changes of the latter.MethodsConcurrently recorded F-VEP and q-EEG were comparatively analysed under Eye-open and Eye-closed Conditions in 11 Controls and 19 AD patients presenting a normal Pattern-Visual Evoked Potential (P-VEP). Between Condition differences in latencies of P2 component were matched to variations in spectral components of q-EEG.ResultsP2 latency increased in 10 AD patients with Abnormal Latency (AD-AL) under Eye-closed Condition. In these patients reduction of alpha activity joined an increased delta power so that their spectral profile equated that recorded under Eye-open Condition. On the opposite, in Controls as well as in AD patients with Normal P2 Latency (AD-NL) spectral profiles recorded under Eye-open and Eye-closed Conditions significantly differed from each other. At the baseline, under Eye-open Condition, the spectra overlapped each other in the three Groups.ConclusionUnder Eye-closed Condition AD patients may present a significant change in both F-VEP latency and EEG rhythm modulation. The presence of concurrent changes of independent parameters suggests that the neurodegenerative process can impair a control system active in Eye-closed Condition which the electrophysiological parameters depend upon. F-VEP can be viewed as a reliable marker of such impairment.

Electrophysiological differences between high and low frequency rTMS protocols in depression treatment.

Repetitive transcranial magnetic stimulation (rTMS) is a rapidly expanding mean in drug resistant depression treatment. Yet, despite vast research in this field, exact neurophysiological mechanism of rTMS therapy still remains unclear. This results in difficulties choosing suitable rTMS parameters in advance and compromises thorough evaluation of efficacy after the treatment. In order to obtain more explicit assessment of rTMS therapy in the psychiatric field, we evaluated and compared the influence of two most widely used antidepressive rTMS protocols on EEG band power spectrum and relation to clinical test scores (MADRS, BDI, HAM-D17). Forty-five patients (12 male, 33 female, mean age 52.16 years) participated in the study. Twenty-three patients received high frequency (10 Hz) stimulation, the rest 22 were stimulated using low frequency (1 Hz) protocol. Both groups received 10 to 15 daily rTMS sessions. EEG recordings and clinical tests were obtained the day before rTMS course and same day after the last session. Majority (57.78%) of patients showed considerable improvement after the treatment. There were no notable differences in clinical test score drop between the two rTMS protocols. However, we found that different protocols resulted in significantly different electrophysiological changes. High frequency (10 Hz) rTMS resulted in widespread changes off EEG band power, including delta power increase on the left hemisphere and alpha power growth on the right. Theta power increase was also obtained in parietal-occipital areas. Low frequency (1 Hz) rTMS showed to have no major effect on basic EEG band power, however, we found a notable shift of frontal alpha power asymmetry towards the right hemisphere, which correlated with the clinical outcome. Our study results suggest that two widely used rTMS protocols strongly differ in their electrophysiological mechanisms. Low frequency stimulation finesse on frontal alpha power asymmetry shift, whereas high frequency protocol acts on wider electrophysiological changes in the brain.

Localized Potentiation of Sleep Slow-Wave Activity Induced by Prefrontal Repetitive Transcranial Magnetic Stimulation in Patients with a Major Depressive Episode

BackgroundThe effects of repetitive transcranial magnetic stimulation (rTMS) on sleep structure in major depression are currently unknown. ObjectiveTo determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in major depression. MethodsIn this open-label pilot study, twelve male patients with relatively mild depression, who had been medication-resistant, underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline, Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session). Discrete Fourier Transform (DFT) band power analyses were performed to quantify delta and sigma band activities during Stages II–IV, and determine time courses of these activities between Baseline and Post-1 (first five sessions) and between Post-1 and Post-2 (last five sessions). ResultsPost-hoc tests based on a three-way ANOVA model indicated significant delta power increase at F3 (t11 = −2.762, P = 0.018) during the first five sessions; however, sigma power was unchanged. No significant band power changes were observed during the second half. Stages II–IV (percent total sleep time) increased significantly during the first half (t12 = −2.43, P = 0.033). No other significant changes in sleep parameters or clinical correlations were observed. ConclusionsThe first five sessions of high frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3, possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This increased activity was not observed during the last half, possibly due to a homeostatic regulation mechanism intrinsic to SWA.

Sleep Phenotyping in a Mouse Model of Extreme Trait Anxiety

BackgroundThere is accumulating evidence that anxiety impairs sleep. However, due to high sleep variability in anxiety disorders, it has been difficult to state particular changes in sleep parameters caused by anxiety. Sleep profiling in an animal model with extremely high vs. low levels of trait anxiety might serve to further define sleep patterns associated with this psychopathology.Methodology/Principal FindingsSleep-wake behavior in mouse lines with high (HAB), low (LAB) and normal (NAB) anxiety-related behaviors was monitored for 24 h during baseline and recovery after 6 h sleep deprivation (SD). The amounts of each vigilance state, sleep architecture, and EEG spectral variations were compared between the mouse lines. In comparison to NAB mice, HAB mice slept more and exhibited consistently increased delta power during non-rapid eye movement (NREM) sleep. Their sleep patterns were characterized by heavy fragmentation, reduced maintenance of wakefulness, and frequent intrusions of rapid eye movement (REM) sleep. In contrast, LAB mice showed a robust sleep-wake rhythm with remarkably prolonged sleep latency and a long, persistent period of wakefulness. In addition, the accumulation of delta power after SD was impaired in the LAB line, as compared to HAB mice.Conclusions/SignificanceSleep-wake patterns were significantly different between HAB and LAB mice, indicating that the genetic predisposition to extremes in trait anxiety leaves a biological scar on sleep quality. The enhanced sleep demand observed in HAB mice, with a strong drive toward REM sleep, may resemble a unique phenotype reflecting not only elevated anxiety but also a depression-like attribute.

Cognitive Enhancement Using 19-ElectrodeZ-Score Neurofeedback

A 23-year-old man presented for a neurological evaluation due to cognitive problems restricting him from college education. He graduated successfully from high school but had problems in college, which caused his subsequent withdrawal. He was interested in trying neurofeedback (NFB) for possible cognitive enhancement. His initial computerized neurocognitive testing showed global cognitive standard score (GCS) of 93.1. The information processing speed standard score was 64.5 and was the lowest of scored domains. Quantitative electroencephalography revealed right frontal and temporal increase in delta power and left frontal and temporal beta power excess. Fifteen sessions of 19-electrode Z-score NFB lead to marked improvement of the patient's subjective cognitive perception as well as GCS on computerized neurocognitive testing. His post-NFB GCS was 104.1 and information-processing speed reached 85.2. Also a reduction of the right frontal and temporal delta power expression was achieved, as well as improveme...