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Objective To evaluate motor fluctuations in patients with advanced Parkinson’s disease (PD) using a small-sized wearable device for surface electromyography (EMG) with accelerometry (ACC) for 24 hours. Methods Seven PD patients with medication were measured once, and nine patients with directional deep brain stimulation (dDBS) twice: before and after the dDBS reprogramming. EMG and ACC parameters were compared with clinical rating scores and patients’ home diaries. Results The combination of EMG and ACC parameters (first principal component PC1) correlated significantly with patient’s condition as quantified by the motor score of Unified Parkinson’s Disease Rating Scale and it changed significantly with dDBS reprogramming in line with decreased PD symptoms. Monitoring data detected in comparison with the home diaries: 91 % concordance with tremor, 76 % with rigidity, and 74 % with dyskinesia. In the DBS group, the wake-up time with abnormal neuromuscular function was reduced with reprogramming in all except one patient based on measurements. Conclusions A wearable device measuring simultaneously both muscle activity and motion can provide continuous and dynamic information about patient’s condition and motor fluctuations at home. Significance The present method may help to modify pharmacologic management and DBS treatment in advanced PD.

Background: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported differentially abundant taxa. The temporal stability of such microbiota alterations and their relationship to disease progression have not been previously studied with a high-throughput sequencing based approach. Methods: We collected clinical data and stool samples from 64 Parkinson's patients and 64 control subjects twice, on average 2.25 years apart. Disease progression was evaluated based on changes in Unified Parkinson's Disease Rating Scale and Levodopa Equivalent Dose, and microbiota were characterized with 16S rRNA gene amplicon sequencing. Findings: We compared patients to controls, and patients with stable disease to those with faster progression. There were significant differences between microbial communities of patients and controls when corrected for confounders, but not between timepoints. Specific bacterial taxa that differed between patients and controls at both timepoints included several previously reported ones, such as Roseburia, Prevotella and Bifidobacterium. In progression comparisons, differentially abundant taxa were inconsistent across methods and timepoints, but there was some support for a different distribution of enterotypes and a decreased abundance of Prevotella in faster-progressing patients. Interpretation: The previously detected gut microbiota differences between Parkinson's patients and controls persisted after 2 years. While we found some evidence for a connection between microbiota and disease progression, a longer follow-up period is required to confirm these findings. (C) 2019 The Authors. Published by Elsevier B.V.

Introduction: Parkinson's disease (PD) is associated with neuropathological changes in olfactory and gastrointestinal tissues, and PD patients frequently suffer from hyposmia, hyposalivation, and dysphagia. Since hyposmia and gastrointestinal dysfunction are frequently premotor symptoms, it has been speculated that an external, for example microbial, agent could trigger the pathologic process in the corresponding organs, subsequently spreading to the central nervous system. We recently showed evidence for compositional differences between the fecal microbiota of PD patients and control subjects. In this study, our objective was to explore a possible connection between nasal and oral microbiota and PD. Methods: We compared the oral and nasal bacterial communities of PD patients (oral: n = 72, nasal: n = 69) and control subjects (oral: n = 76, nasal: n = 67) using a 16S rRNA gene amplicon sequencing approach. Results: Oral and nasal microbiota differed markedly from each other, with no notable similarity within subjects. Oral microbiota of PD patients and control subjects had differences in beta diversity and abundances of individual bacterial taxa. An increase in the abundance of opportunistic oral pathogens was detected in males, both with and without PD. Our data did not reveal convincing differences between the nasal microbiota of control subjects and PD patients. Conclusion: The oral microbiome deserves additional research regarding its connection to PD and its biomarker potential. The higher abundance of oral pathogens in men underlines the importance of monitoring and promoting male dental health. (C) 2017 Elsevier Ltd. All rights reserved.

Objective: Electromyography (EMG) and acceleration (ACC) measurements are potential methods for quantifying efficacy of deep brain stimulation (DBS) treatment in Parkinson's disease (PD). The treatment efficacy depends on the settings of DBS parameters (pulse amplitude, frequency and width). This study quantified, if EMG and ACC signal features differ between different DBS settings and if DBS effect is unequal between different muscles. Methods: EMGs were measured from biceps brachii (BB) and tibialis anterior (TA) muscles of 13 PD patients. ACCs were measured from wrists. Measurements were performed during seven different settings of DBS and analyzed using methods based on spectral analysis, signal morphology and nonlinear dynamics. Results: The results showed significant within-subject differences in the EMG signal kurtosis, correlation dimension, recurrence rate and EMG-ACC coherence between different DBS settings for BB but not for TA muscles. Correlations between EMG feature values and clinical rest tremor and rigidity scores were weak but significant. Conclusions: Surface EMG features differed between different DBS settings and DBS effect was unequal between upper and lower limb muscles. Significance: EMG changes pointed to previously defined optimal settings in most of patients, which should be quantified even more deeply in the upcoming studies. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective Cortico-muscular coherence (CMC) is thought to reflect the interplay between cortex and muscle in motor coordination. In Parkinson's disease (PD) patients, levodopa has been shown to enhance CMC. This study examined whether subthalamic nucleus (STN) deep brain stimulation (DBS) affects the CMC in advanced PD. Methods Magnetoencephalography (MEG) and electromyography (EMG) measurements were done simultaneously both with DBS on and off to determine the CMC during wrist extension. The spatiotemporal signal space separation (tSSS) was used for artifact suppression. Results CMC peaks between 13 and 25Hz were found in 15 out of 19 patients. The effect of DBS on CMC was variable. Moreover, the correlation between CMC and motor performance was inconsistent; stronger CMC did not necessarily indicate better function albeit tremor and rigidity may diminish the CMC. Patients having CMC between 13 and 25Hz had the best motor scores at the group level. Conclusions DBS modifies the CMC in advanced PD with large interindividual variability. Significance DBS does not systematically modify CMC amplitude in advanced PD. The results suggest that some components of the CMC may be related to the therapeutic effects of DBS.

Objective To investigate the effects of cortical ischemic stroke and aphasic symptoms on auditory processing abilities in humans as indicated by the transient brain response, a recently documented cortical deflection which has been shown to accurately predict behavioral sound detection. Methods Using speech and sinusoidal stimuli in the active (attend) and the passive (ignore) recording condition, cortical activity of ten aphasic stroke patients and ten control subjects was recorded with whole-head MEG and behavioral measurements. Results Stroke patients exhibited significantly diminished neuromagnetic transient responses for both sinusoidal and speech stimulation when compared to the control subjects. The attention-related increase of response amplitude was slightly more pronounced in the control subjects than in the stroke patients but this difference did not reach statistical significance. Conclusions Left-hemispheric ischemic stroke impairs the processing of sinusoidal and speech sounds. This deficit seems to depend on the severity and location of stroke. Significance Directly observable, non-invasive brain measures can be used in assessing the effects of stroke which are related to the behavioral symptoms patients manifest.

Using magnetoencephalography (MEG) and auditory sinusoidal and speech stimuli slowly rising in intensity over a period of 750 ms, we studied ten stroke patients and ten control subjects. Both in the passive and the active recording conditions, the stroke patients exhibited significantly smaller brain response amplitudes than the healthy controls. Cortical stroke appears to have a marked effect on the amplitude dynamics of the auditory evoked activity at the level of basic stimulus feature analysis and on the cognitive control related to attentional engagement.

Abnormal low-frequency entrainment in sensorimotor cortical areas of Parkinson's disease (PD) patients has been observed in MEG recordings. Efficacy of high-frequency stimulation of subthalamic nucleus (STN) in treating PD may result from blocking such abnormal oscillations. Artifacts elicited by stimulation have precluded MEG study of such patients. We recorded spontaneous MEG activity with a 306-channel Elekta Neuromag® instrument from a Parkinsonian patient with an implanted neurostimulator, with electrodes in both subthalamic nuclei when 130-Hz STN stimulation was on and off. Auditory evoked fields (AEFs) were recorded as well. Brain activity was revealed by applying temporally extended signal space separation on the signals strongly contaminated by stimulation-related artifacts. Bipolar STN stimulation decreased spontaneous activity in the 3–20 Hz range over the right sensorimotor cortex both when eyes were open and closed. Less systematic changes were observed over the left hemisphere where monopolar stimulation was associated with an increase of the low-frequency activity. Suppression of occipital alpha activity in eyes open condition as well as AEF source locations corresponded with those in normal subjects. The results suggest that STN stimulation modifies spontaneous activity over the sensorimotor cortices.

Therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) are extensively studied in patients with Parkinson's disease (PD). rTMS to primary motor cortex (M1) induces dopamine release in the putamen: consequently M1 is an interesting target for rTMS in PD. The rTMS over M1 in PD patients reduces the reaction time, improves the Unified Parkinson's Disease Rating Scale (UPDRS) scores and alleviates bradykinesia and hypokinesia. However, the effects of rTMS on spontaneous brain activity are not known. We investigated whether subthreshold rTMS to M1 modulated spontaneous oscillations recorded with magnetoencephalography (MEG). MEG from nine medicated, non-demented PD patients displayed a significant increase in beta oscillations after rTMS in the stimulated hemisphere. Minimum current estimate calculations revealed an increase of beta oscillatory activity after the rTMS treatment over the Rolandic regions. The rTMS in PD patients alters spontaneous brain activity as seen with MEG, probably by modulating cortico-thalamo-basal ganglia networks.

Using magnetoencephalography (MEG), we studied nine healthy young subjects and presented them with auditory sinusoidal stimuli or spectrally complex speech sounds rising in intensity over a duration of 750 ms. The speech sounds elicited more prominent transient brain activity than their frequency-matched sinusoidal counterparts. Attentional engagement further enhanced the amplitude of the responses for both stimulus types. The findings hold promise for both basic and applied research.

The effects of aging in the cortical processing of auditory stimuli were studied using whole-head magnetoencephalography (MEG) and long-duration stimuli slowly rising in intensity. The stimuli were 750-ms sinusoids or speech sounds. The two subject groups (N=9+9) studied were, on the average, 61 and 24 years of age. It was found that aging results in considerable delays in averaged transient brain activity. © 2007 Elsevier B.V. All rights reserved.

Down syndrome (DS) is characterized by intellectual disability and development of dementia that are attributed to similar neuropathological features as observed in Alzheimer's disease (AD). The aim of this study was to investigate whether DS patients have similar impairment of preattentive auditory processing as observed in AD. Sinusoidal tones were presented to DS patients and healthy controls, and evoked auditory evoked fields (AEF) were measured with a whole-head magnetoencephalography (MEG) system. Patients with DS had significantly delayed and attenuated N100m, and delayed but not attenuated P50m responses over both hemispheres. Present results indicate that preattentive auditory processing underlying stimulus detection is impaired in DS. Given that anticholinergic drugs modulate AEFs, degeneration of cholinergic system in DS could contribute to the damaged auditory processing.

Slowing of spontaneous alpha oscillations and an anterior shift of a source of alpha activity (8–13 Hz) have been consistently reported in the EEG studies of Alzheimer's disease (AD). It is unknown whether these changes are associated with a gradual shift in location and frequency of existing sources or rather with the involvement of a new set of oscillators. We addressed this question by applying source modeling (minimum current estimates, MCE) to spontaneous alpha activity recorded with a 306-channel MEG system from eleven non-medicated AD patients with mild to moderate cognitive impairment and twelve age-matched controls during the eyes-closed session. AD patients had predominant lower alpha band sources in the temporal regions, whereas in the controls, robust alpha sources were found near the parieto-occipital sulcus. Activation within the parieto-occipital region was significantly weaker, and activation in the right temporal area was significantly enhanced in the AD patients. These results suggest an increased temporal-lobe contribution coinciding with parieto-occipital deficits. We propose that MCE, which provides simultaneous mapping of several oscillatory sources, might be useful for detecting neurophysiological abnormalities associated with AD in combination with other neuropsychological and neurological measures.

Auditory event-related potential (ERP) components P50 and N100 are thought to index preattentive auditory processing underlying stimulus detection, whereas a subsequent component termed mismatch negativity (MMN) has been proposed to reflect comparison of incoming stimuli to a short-lived sensory memory trace of preceding sounds. Existing evidence suggests impairment of preattentive auditory processing in aging, which appears to be accompanied by decline of cholinergic activity. Previous studies indicate that scopolamine, which is a centrally acting muscarinic receptor antagonist, modulates preattentive auditory processing in young subjects. It has remained elusive, however, to which extent scopolamine affects preattentive auditory processing in aged subjects. We measured auditory responses simultaneously with electroencephalogram (EEG) and magnetoencephalogram (MEG) from nine non-demented elderly subjects after intravenous injection of scopolamine or glycopyrrolate, the latter being a peripherally acting cholinergic antagonist, using a double blind protocol. Scopolamine significantly delayed electric P50, both electric and magnetic N100 responses, whereas subsequent MMN and P200 responses were not altered by scopolamine. Our results indicate that the cholinergic system modulates auditory processing underlying stimulus detection in aging. In addition, auditory evoked responses appear to have different age-related sensitivity to cholinergic modulation. The combined MEG/EEG measurements using particularly auditory N100 response might offer an objective tool to monitor cholinergic activity in aging and Alzheimer's disease (AD).

Objective : The effects on cortical rhythms of a single-dose (30 μg/kg) administration of the GABA A agonist lorazepam were examined in a randomized, double-blind, cross-over, placebo-controlled study with 8 healthy volunteers using simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Methods : The oscillations were assessed by means of adaptive classification of short-term spectral patterns. Results : Lorazepam (a) decreased the percentage of EEG/MEG segments with fast-theta, delta-alpha, fast-theta–alpha and alpha activity and increased percentage of EEG/MEG segments with delta, delta–slow-theta, delta–beta, slow-theta and polyrhythmic activity; (b) decreased diversity of EEG/MEG signals (in terms of spectral patterns) and increased the general instability of the signal; (c) increased stabilization periods of the spectral patterns (reduced brain information processing); (d) maintained larger maximum periods of temporal stabilization for delta, slow-theta, delta–slow-theta, delta–beta and polyrhythmic activity (in terms of spectral patterns); (e) did not increase power in the independent beta rhythm. Conclusions : Lorazepam caused significant reorganization of the EEG/MEG microstructure. These results suggest also that adaptive classification analysis of single short-term spectral patterns may provide additional information to conventional spectral analyses.

Objective : Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron damage that gives rise to muscle denervation. Besides motor neuron damage, conscious auditory processing appears to be impaired in ALS, whereas it has remained ambiguous whether preceding automatic auditory processing is abnormal in ALS and specifically in ALS with bulbar signs. Methods : Auditory evoked fields (AEFs) to monaurally presented frequent and infrequent tones with stimulus intervals of 500 and 2500 ms were recorded with magnetoencephalography (MEG) from 10 ALS patients having bulbar signs and from 10 age-matched healthy subjects. Results : The amplitudes of the P50m and N100m responses, which index automatic auditory processing underlying stimulus detection, were significantly increased and P50m latency was shortened in ALS patients. MMNm, which reflects memory-based auditory comparison process, was increased in amplitude in the patient group, whereas the MMNm latency was similar in both groups. AEF latency and amplitude values failed to correlate with the severity of ALS as measured by ALS Functional Rating Scale (ALSFRS). Conclusions : The present results suggest that auditory processing underlying stimulus detection, and subsequent memory-based comparison processes are abnormal in ALS patients with severe bulbar signs. This might be due to cortical overactivity of excitatory neurotransmitter glutamate observed in ALS.

Cognitive processes including selective attention may depend on synchronous activity of neurons at the gamma-band (around 40 Hz). To determine the effect of neuroleptic challenge on transient auditory evoked 40-Hz response, simultaneous measurement of 122-channel magnetoencephalogram (MEG) and 64-channel electroencephalogram (EEG) was used. Either 2 mg of dopamine D2-receptor antagonist haloperidol or a placebo was administered orally to 11 healthy subjects in a double-blind randomized crossover design in two separate sessions. The subjects attended to tones presented to one ear and ignored those presented to the other ear. Haloperidol significantly suppressed the transient 40-Hz electric response to the attended stimuli, while no significant effect was observed in the electric responses to the unattended tones or in the magnetic responses. The present result suggests that dopamine D2 receptors modulate selective attention.

First weeks after alcohol withdrawal, associated with profound changes in neural transmission, constitute the critical period for relapse prevention and pharmacological intervention in alcoholism. Here, 20 male alcoholics with 1-6 weeks of abstinence and 20 age-matched healthy controls were studied using auditory event-related potentials (ERP), measured with a 32-channel electroencephalogram, and neuropsychological tests of auditory-verbal memory. Global field power maximum of ERP during 80-150 ms period after presentation of unattended tones (binaural 700 Hz pure tones, inter-stimulus interval 2.5 s) was significantly (P

Auditory electric and magnetic P50(m), N1(m) and MMN(m) responses to standard, deviant and novel sounds were studied by recording brain electrical activity with 25 EEG electrodes simultaneously with the corresponding magnetic signals measured with 122 MEG gradiometer coils. The sources of these responses were located on the basis of the MEG responses; all were found to be in the supratemporal plane. The goal of the present paper was to investigate to what degree the source locations and orientations determined from the magnetic data account for the measured EEG signals. It was found that the electric P50, N1 and MMN responses can to a considerable degree be explained by the sources of the corresponding magnetic responses. In addition, source-current components not detectable by MEG were shown to contribute to the measured EEG signals.

It has been suggested that schizophrenic patients fail to develop left-hemisphere dominance because of an early disturbance in neuronal development. This hypothesis has been supported by some post-mortem. CT and magnetic resonance imaging (MRI) studies, while other in-vivo studies have given contradicting results. We used 122-channel whole-head magnetoencephalography and MRI to locate the sources of auditory evoked responses in 19 schizophrenic patients and in 20 healthy controls. Auditory evoked responses were detected in all subjects. The left-right hemisphere asymmetry of cerebral sources for auditory evoked responses was markedly dispersed among patients when compared with controls. The source locations for left auditory cortex were clearly anterior with respect to the right hemisphere in 32% of the patients, while the corresponding prevalence of this abnormal asymmetry was 0% in controls (p = 0.008. Fisher's exact test). The reversed asymmetry appeared to be associated with a shorter anterior-posterior distance between the auditory cortex and the anterior tip of the temporal lobe in the left side when compared with the right side. The reversed asymmetry was associated with higher PANSS general psychopathological score, and especially with higher guilt feelings and motor retardation scores. The large 2.5-fold standard deviation in the inter-hemispheric anterior posterior difference in the location of the auditory cortex among patients (p 0.001 for the difference in the magnitude of variance between controls and patients) clearly reflects the dispersion of the left right asymmetry into both direction, and three of the patients with 'normal asymmetry' had a greater left-right asymmetry than any of the controls. Markedly greater reversal of hemispheric asymmetry among patients implies that regulation of the development of brain asymmetry is disturbed among schizophrenic patients. Abnormality in the cerebral asymmetry may be a crucial factor in the development of schizophrenic disorder in a substantial proportion of patients. The results suggest that the reversed asymmetry is associated with the higher severity of general psychopathological symptoms.

Effects of ethanol (0.55 and 0.85 g/kg) on event-related potentials were investigated by presenting 50-ms standard and 25-ms deviant pure tones to 9 social drinkers during a reading task, in a single-blind, placebo-controlled paradigm. Whereas the lower ethanol dose had no impact on ERPs with an 0.8-s inter-stimulus interval (ISI), it attenuated the N1, P2, and mismatch negativity (MMN) amplitudes with a longer ISI of 2.4 s. The higher alcohol dose increased the N1 peak latency with both ISIs. It also suppressed the N1 and MMN amplitudes with the longer ISI. The MMN suppression did not, however, occur at scalp sites below the Sylvian fissure, thus suggesting that ethanol affected only the frontal MMN subgenerator. Moreover, the different dose responses of the N1, P2, and MMN (subcomponents) to ethanol may indicate that the neurotransmitter systems underlying their generation are, to some extent, different.

The deviant tones embedded in a sequence of standard tones elicit an event-related potential (ERP) component called mismatch negativity (MMN). Because MMN is partly overlapped by other ERP components at 100–200 msec latency (N1 and P2) and its shape varies, MMN peak latency and amplitude may be ambiguous. We used the difference area between the deviant and standard ERP to evaluate the age and interstimulus interval (ISI) dependence of MMN. Sequences of standard (85%) and deviant (15%) tones were presented to 27 normal subjects (age 18–85 years) using 1 sec and 3 sec ISIs and to 6 young subjects using an additional ISI of 5 sec. With this method MMN was clearly seen in 26 out of 27 healthy subjects (96.3%). MMN area was quite stable regardless of age with 1 sec ISI. With 3 sec ISI MMN area was significantly smaller in the old than in the young subjects. This may reflect the shortening of the sensory auditory memory trace with increasing age.

To discern the role of the GABA A receptors in the generation and attentive modulation of the transient auditory 40-Hz response, the effects of the benzodiazepine temazepam (10 mg) were studied in 10 healthy social drinkers, using a double-blind placebo-controlled design. Three hundred Hertz standard and 330 Hz rare deviant tones were presented to the left, and 1000 Hz standards and 1100 Hz deviants to the right ear of the subjects. Subjects attended to a designated ear and were to detect deviants therein while ignoring tones to the other. Temazepam significantly suppressed the amplitude of the 40-Hz response, the effect being equal for attended and non-attended tone responses. This suggests involvement of GABA A receptors in transient auditory 40-Hz response generation, however, not in the attentive modulation of the 40-Hz response.