Periklis Y. Ktonas

Transcranial Direct Current Stimulation Effects in Disorders of Consciousness

OBJECTIVEnTo assess the efficacy of transcranial direct current stimulation (tDCS) on improving consciousness in patients with persistent unresponsive wakefulness syndrome (UWS) (previously termed persistent vegetative state [PVS]) or in a minimally conscious state (MCS).nnnDESIGNnProspective, case series trial with follow-up at 12 months.nnnSETTINGnGeneral and research hospital.nnnPARTICIPANTSnInpatients in a PVS/UWS or MCS (N=10; 7 men, 3 women; age range, 19-62y; etiology: traumatic brain injury, n=5; anoxia, n=4; postoperative infarct, n=1; duration of PVS/UWS or MCS range, 6mo-10y). No participant withdrew because of adverse effects.nnnINTERVENTIONnAll patients received sham tDCS for 20 minutes per day, 5 days per week, for 1 week, and real tDCS for 20 minutes per day, 5 days per week, for 2 weeks. An anodal electrode was placed over the left primary sensorimotor cortex or the left dorsolateral prefrontal cortex, with cathodal stimulation over the right eyebrow. One patient in an MCS received a second round of 10 tDCS sessions 3 months after initial participation.nnnMAIN OUTCOME MEASUREnJFK Coma Recovery Scale-Revised.nnnRESULTSnAll patients in an MCS showed clinical improvement immediately after treatment. The patient who received a second round of tDCS 3 months after initial participation showed further improvement and emergence into consciousness after stimulation, with no change between treatments. One patient who was in an MCS for <1 year before treatment (postoperative infarct) showed further improvement and emergence into consciousness at 12-month follow-up. No patient showed improvement before stimulation. No patient in a PVS/UWS showed immediate improvement after stimulation, but 1 patient who was in a PVS/UWS for 6 years before treatment showed improvement and change of status to an MCS at 12-month follow-up.nnnCONCLUSIONSntDCS seems promising for the rehabilitation of patients with severe disorders of consciousness. Severity and duration of pathology may be related to the degree of tDCS beneficial effects.

Sleep spindle detection using artificial neural networks trained with filtered time-domain EEG: A feasibility study

An artificial neural network (ANN) based on the Multi-Layer Perceptron (MLP) architecture is used for detecting sleep spindles in band-pass filtered electroencephalograms (EEG), without feature extraction. Following optimum classification schemes, the sensitivity of the network ranges from 79.2% to 87.5%, while the false positive rate ranges from 3.8% to 15.5%. Furthermore, due to the operation of the ANN on time-domain EEG data, there is agreement with visual assessment concerning temporal resolution. Specifically, the total inter-spindle interval duration and the total duration of spindles are calculated with 99% and 92% accuracy, respectively. Therefore, the present method may be suitable for investigations of the dynamics among successive inter-spindle intervals, which could provide information on the role of spindles in the sleep process, and for studies of pharmacological effects on sleep structure, as revealed by the modification of total spindle duration.

Sleep disturbances in relation to fatigue in major depression.

OBJECTIVEnThis study aimed to investigate the independent correlations of subjective sleep disturbances (insomnia and daytime sleepiness) with the severity of fatigue in patients with major depression.nnnMETHODSnEighty-one currently depressed patients (70 females and 11 males), aged between 23 and 65 years, with a DSM-IV diagnosis of major depressive disorder were studied. Patients with physical diseases or other conditions associated with prominent fatigue were excluded. The 17-item Hamilton Depression Rating Scale (HDRS), the Athens Insomnia Scale (AIS), and the Epworth Sleepiness Scale (ESS) were used for the cross-sectional assessment of the severity of depression, insomnia, and sleepiness, respectively. Severity of fatigue was measured with the Fatigue Severity Scale (FSS). Pearsons and Spearmans coefficients were used in bivariate correlations between FSS score and the independent variables (age, gender, inpatient/outpatient status, HDRS score, AIS total score, AIS individual item scores, and ESS score). A stepwise multiple regression analysis was then performed, with FSS score as the dependent variable.nnnRESULTSnThe severity of fatigue was significantly correlated with female sex, HDRS score, AIS total score, awakenings during the night (AIS item 2), compromised sleep quality (AIS item 5), and ESS score. Sleep quality (AIS item 5) and daytime sleepiness (ESS) were the only significant predictors of the severity of fatigue in the multiple regression analysis.nnnCONCLUSIONSnBoth sleep quality and daytime sleepiness correlate independently with fatigue severity, as measured with the FSS, in patients with major depression. The FSS does not appear to be a pure measure of fatigue in depressed patients, a finding with potential implications for the choice of appropriate fatigue measures in this population.

Time-frequency analysis methods to quantify the time-varying microstructure of sleep EEG spindles: Possibility for dementia biomarkers?

The time-varying microstructure of sleep EEG spindles may have clinical significance in dementia studies and can be quantified with a number of techniques. In this paper, real and simulated sleep spindles were regarded as AM/FM signals modeled by six parameters that define the instantaneous envelope (IE) and instantaneous frequency (IF) waveforms for a sleep spindle. These parameters were estimated using four different methods, namely the Hilbert transform (HT), complex demodulation (CD), matching pursuit (MP) and wavelet transform (WT). The average error in estimating these parameters was lowest for HT, higher but still less than 10% for CD and MP, and highest (greater than 10%) for WT. The signal distortion induced by the use of a given method was greatest in the case of HT and MP. These two techniques would necessitate the removal of about 0.4s from the spindle data, which is an important limitation for the case of spindles with duration less than 1s. Although the CD method may lead to a higher error than HT and MP, it requires a removal of only about 0.23s of data. An application of this sleep spindle parameterization via the CD method is proposed, in search of efficient EEG-based biomarkers in dementia. Preliminary results indicate that the proposed parameterization may be promising, since it can quantify specific differences in IE and IF characteristics between sleep spindles from dementia subjects and those from aged controls.

Independent component analysis for source localization of EEG sleep spindle components

Sleep spindles are bursts of sleep electroencephalogram (EEG) quasirhythmic activity within the frequency band of 11–16u2009Hz, characterized by progressively increasing, then gradually decreasing amplitude. The purpose of the present study was to process sleep spindles with Independent Component Analysis (ICA) in order to investigate the possibility of extracting, through visual analysis of the spindle EEG and visual selection of Independent Components (ICs), spindle “components” (SCs) corresponding to separate EEG activity patterns during a spindle, and to investigate the intracranial current sources underlying these SCs. Current source analysis using Low-Resolution Brain Electromagnetic Tomography (LORETA) was applied to the original and the ICA-reconstructed EEGs. Results indicated that SCs can be extracted by reconstructing the EEG through back-projection of separate groups of ICs, based on a temporal and spectral analysis of ICs. The intracranial current sources related to the SCs were found to be spatially stable during the time evolution of the sleep spindles.

Transcranial alternating current stimulation reduces symptoms in intractable idiopathic cervical dystonia: a case study.

Idiopathic cervical dystonia (ICD) is a movement disorder often resulting in profound disability and pain. Treatment options include oral medications or other invasive procedures, whereas intractable ICD has been shown to respond to invasive (deep) brain stimulation. In the present blinded, placebo-controlled case study, transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) has been applied to a 54-year old patient with intractable ICD. Results showed that 15 Hz tACS had both immediate and cumulative effects in dystonic symptom reduction, with a 54% reduction in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score, and a 75% in the TWSTRS Pain Scale. These effects were persistent at 30-days follow-up. This is the first report to demonstrate a significant and lasting therapeutic effect of non-invasive electrical brain stimulation in dystonia.

Sleep in frontotemporal dementia is equally or possibly more disrupted, and at an earlier stage, when compared to sleep in Alzheimer's disease.

BACKGROUNDnConversely to other neurodegenerative diseases (i.e., Alzheimers disease, AD), sleep in frontotemporal dementia (FTD) has not been studied adequately. Although some evidence exists that sleep-wake disturbances occur in FTD, very little is known regarding sleep macrostructure and/or primary sleep disorders.nnnOBJECTIVEnTo investigate these issues in this population and compare them to similar issues in AD and in healthy elderly (HE).nnnMETHODSnTwelve drug-naïve behavioral-variant FTD (bvFTD) patients (7 men/5 women) of mean age 62.5 ± 8.6 years were compared to seventeen drug-naïve AD patients (8 men/9 women) of mean age 69.0 ± 9.9 years and twenty drug-naïve HE (12 men/8 women) of mean age 70.2 ± 12.5 years. All participants were fully assessed clinically, through a sleep questionnaire, an interview, and video-polysomnography recordings.nnnRESULTSnThe two patient groups were comparably cognitively impaired. However, compared to FTD patients, the AD patients had a statistically significant longer disease duration. Overall, the sleep profile was better preserved in HE. Sleep complaints did not differ considerably between the two patient groups. Sleep parameters and sleep macrostructure were better preserved in AD compared to FTD patients, regardless of primary sleep disorders, which occurred equally in the two groups.nnnCONCLUSIONSnWith respect to AD, FTD patients had several sleep parameters similarly or even more affected by neurodegeneration, but in a much shorter time span. The findings probably indicate a centrally originating sleep deregulation. Since in FTD patients sleep disturbances may be obvious from an early stage of their disease, and possibly earlier than in AD patients, physicians and caregivers should be alert for the early detection and treatment of these symptoms.

Non-rapid eye movement sleep instability in mild cognitive impairment: a pilot study

OBJECTIVEnPolysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limited only to conventional sleep parameters. The aim of our study was to evaluate sleep architecture and cyclic alternating pattern (CAP) parameters in subjects with MCI, and to assess their eventual correlation with cognition.nnnMETHODSnEleven subjects with MCI (mean age 68.5u2009±u20097.0 years), 11 patients with mild probable Alzheimers disease (AD; mean age 72.7u2009±u20095.9 years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively intact healthy elderly individuals (mean age 69.2u2009±u200912.6 years) underwent ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP parameters.nnnRESULTSnRapid eye movement sleep, CAP rate, and CAP slow components (A1 index) were decreased in MCI subjects and to a greater extent in AD patients, compared to cognitively intact controls. AD showed also decreased slow wave sleep (SWS) relative to healthy elderly individuals. MCI nappers showed decreased nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations between sleep variables and neuropsychological tests were found.nnnCONCLUSIONSnMCI and AD subjects showed a decreased sleep instability correlated with their cognitive decline. Such a decrease may be considered as a potential biomarker of underlying neurodegeneration.

Potential dementia biomarkers based on the time-varying microstructure of sleep EEG spindles

The time-varying microstructure of sleep EEG spindles may have clinical significance in dementia studies. In this work, the sleep spindle is modeled as an AM-FM signal and parameterized in terms of six parameters, three quantifying the instantaneous envelope (IE) and three quantifying the instantaneous frequency (IF) of the spindle model. The IE and IF waveforms of sleep spindles from patients with dementia and normal controls were estimated using the time-frequency technique of complex demodulation (CD). Sinusoidal curve-fitting using a matching pursuit (MP) approach was applied to the IE and IF waveforms for the estimation of the six model parameters. Specific differences were found in sleep spindle instantaneous frequency dynamics between spindles from dementia subjects and spindles from controls.

Single-trial magnetoencephalography signals encoded as an unfolding decision process

The model of a stochastic decision process unfolding in motor and premotor regions of the brain was encoded in single-trial magnetoencephalographic (MEG) recordings while ten healthy subjects performed a sensorimotor Reaction Time (RT) task. The duration of single-trial MEG signals preceding the motor response, recorded over the motor cortex contralateral to the responding hand, co-varied with RT across trials according to the models prediction. Furthermore, these signals displayed the same properties of a rising-to-a-fixed-threshold decision process as posited by the model and observed in the activity of single neurons in the primate cortex. The present findings demonstrate that non-averaged, single-trial MEG recordings can be used to test models of cognitive processes, like decision-making, in humans.