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Background Gut microbiota alterations have been found in prodromal and established Parkinson's disease (PD). Antibiotic exposure can have long-term effects on the composition of human intestinal microbiota, but a potential connection between antibiotic exposure and risk of PD has not been studied previously. Objective To evaluate the impact of antibiotic exposure on the risk of PD in a nationwide, register-based, case-control study. Methods We identified all patients who were diagnosed with PD in Finland during the years 1998 to 2014. Information was obtained on individual purchases of orally administered antibiotics during the years 1993 to 2014. We assessed the association between prior antibiotic exposure and PD using conditional logistic regression. Results The study population consisted of 13,976 PD cases and 40,697 controls. The strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416; 95% confidence interval, 1.053-1.904). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10 to 15 years before the index date, sulfonamides and trimethoprim 1 to 5 years before the index date, and antifungal medications 1 to 5 years before the index date were positively associated with PD risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics. Conclusions Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period. The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this. (c) 2019 International Parkinson and Movement Disorder Society

Background Dystonia is a group of chronic diseases, causing considerable physical and psychosocial stress to patients and health care expenses. We studied the prevalence of different dystonia types in Finland in the years 2007–2016. Methods All patients with an ICD-10 code of dystonia were retrieved from the national care register. Average age-adjusted yearly prevalence was assessed for adult-onset isolated idiopathic or hereditary dystonia types from patient records from the Uusimaa and Pirkanmaa provinces. Results 1316 patients were confirmed to have adult-onset isolated idiopathic or hereditary dystonia based on hospital records from two provinces. On average, the age-adjusted prevalence for all adult-onset dystonia was 405 per million and for cervical dystonia 304 per million. For other dystonia types the prevalence ranged from 1–33 per million. Conclusions Adult onset cervical dystonia was the most common type of dystonia with relatively high prevalence in Finland compared with other countries. The prevalence of other types of dystonia was similar compared with other European studies. The higher prevalence of cervical dystonia may be partially explained by the better coverage of patients in public health care, but genetic and exogenous factors might contribute to it.

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.

Levodopa medication is the most efficient treatment for motor symptoms of Parkinson's disease (PD). Levodopa significantly alleviates rigidity, rest tremor, and bradykinesia in PD. The severity of motor symptoms can be graded with UPDRS-III scale. Levodopa challenge test is routinely used to assess patients' eligibility to deep-brain stimulation (DBS) in PD. Feasible and objective measurements to assess motor symptoms of PD during levodopa challenge test would be helpful in unifying the treatment. Twelve patients with advanced PD who were candidates for DBS treatment were recruited to the study. Measurements were done in four phases before and after levodopa challenge test. Rest tremor and rigidity were evaluated using UPDRS-III score. Electromyographic (EMG) signals from biceps brachii and kinematic signals from forearm were recorded with wireless measurement setup. The patients performed two different tasks: arm isometric tension and arm passive flexion-extension. The electromyographic and the kinematic signals were analyzed with parametric, principal component, and spectrum-based approaches. The principal component approach for isometric tension EMG signals showed significant decline in characteristics related to PD during levodopa challenge test. The spectral approach on passive flexion-extension EMG signals showed a significant decrease on involuntary muscle activity during the levodopa challenge test. Both effects were stronger during the levodopa challenge test compared to that of patients' personal medication. There were no significant changes in the parametric approach for EMG and kinematic signals during the measurement. The results show that a wireless and wearable measurement and analysis can be used to study the effect of levodopa medication in advanced Parkinson's disease.

While the etiology and pathogenesis of Parkinson's disease (PD) is still obscure, there is evidence for lifestyle factors influencing disease risk. Best established are the inverse associations with smoking and coffee consumption. In other contexts there is evidence that health effects of lifestyle factors may depend on gut microbiome composition. Considering the gastrointestinal involvement in PD, it was recently speculated, that the associations between smoking, coffee, and PD risk could be mediated by gut microbiota. Here we review such a possible mediatory role of gut microbiota taking into account recent findings on microbiome composition in PD and extending the scope also to urate.

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.

In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker.

Objectives: To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. Methods: We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. Results: At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. Conclusions: STN-DBS improves motor function and enables the reduction in anti-parkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted.

Sudden memory loss, with prolonged cognitive deterioration, clinically initially resembling a transitory global amnesia (TGA)-like episode, might be caused by ischemic stroke in the hippocampal regions. We report a patient with TGA-type sudden anterograde amnesia and normal head CT. Examinations revealed that the patient had several vascular risk factors and 3 tesla (T) head MRI showed ischemic lesions in diffusion-weighted images (DWI) in both hippocampi. Neuropsychological assessment revealed sustained moderate verbal memory deterioration and abnormal executive functions. We suggest that small ischemic strokes in hippocampal regions might remain unrecognized and underdiagnosed if follow-up of TGA-type episodes is not adequate and if head CT remains the only method of brain imaging.

The treatment of Parkinson's disease may be initiated with dopamine agonist or MAO-B-inhibitor for people under 60-65 years of age. For older patients, the treatment may also be started with levodopa. If there are motor complications, such as on-off-symptoms, apomorphin injections can be beneficial in addition to other medications. In the case of difficult on-off-symptoms and dyskinesias in spite of optimal treatment, deep brain stimulation, duodenal levodopa infusion and apomorphine infusion should be considered. Rehabilitation can improve gait speed and balance, decrease falls and improve speech. However, with advancing disease the results are not maintained if trainino is discontinued.

Levodopa is the main treatment method for reducing the symptoms of Parkinson's disease. Whereas it reduces the motor symptoms efficiently, its effect on autonomous nervous system is not clear. The information about effect of levodopa on heart rate variability is not coherent between the studies. In this study, ECG of 11 patients with Parkinson's disease was measured during levodopa challenge with pronounced dose of fast release levodopa to ensure the positive drug effect for deep brain stimulation treatment. Heart rate variability analysis was done at three time points, before administration of levodopa, 30 and 60 minutes after administration. After 30 minutes of administration, the HRV parameters show that parasympathetic nervous system activity is decreased and the sympatho-vagal balance is shifted towards sympathetic control. At 60 minutes after administration the parasympathetic nervous system activates slightly and causes a decrease in heart rate.

Tremor is a common motor disorder, in many diseases. Healthy persons may have low-amplitude physiological action tremor without any functional handicap, contrary to the disabling pathologic tremor. There are numerous types of tremor, and their etiology is poorly known. Tremor can at best be alleviated by drug therapy, but the response may abate with time. Deep brain stimulation has recently been increasingly utilized in the treatment of drug-resistant tremor in various neurologic diseases.

Background Non-motor symptoms are a major contributor to quality of life in patients with advanced Parkinson's disease (PD). Duodenal levodopa infusion (DLI) has been shown to alleviate motor fluctuations, but data on its possible effect on non-motor symptoms are scarce. The aim of the study was to assess the effect of DLI on blood pressure (BP), sweating, and non-motor symptoms. Methods We evaluated prospectively and open-label nine male patients with advanced PD (age 68.5 ± 6.2 years) treated with DLI because of daily motor fluctuations. Patients were evaluated using orthostatic test, sweating and skin temperature measurements, Unified Parkinson's Disease Rating Scale (UPDRS), Non-motor Symptom Scale (NMSS), and PDQ-39 before and after 2 months of treatment. Results Orthostatic BP drop worsened after 1 week of DLI compared with oral medication (24.1 vs 11.9 mmHg, P = 0.011) and remained significant after 2 months of treatment. UPDRS motor scores improved significantly in 2 months compared with baseline (25 vs 19, P

Background: We present here a case of haemorrhagic brain infarction in a middle-aged and physically active male, who had never smoked. This case report aims to remind the internist and neurologist to bear in mind unusual aetiologies of brain infarcts in patients without classical cardiovascular risk factors. Case Description: A 49-year-old male with pulmonary asthma and a prior history of nasal polyps had a wake-up stroke with left-sided symptoms and speech disturbance. A head MRI and MR angiography revealed a recent haemorrhagic infarct in the right putamen and corona radiata. The left hemiparesis progressed to sensory-motor hemiplegia on the 4th day. In the head CT, it was shown that the haemorrhagic infarct had progressed to a large haematoma. A pansinusitis was also diagnosed. The aetiological investigations revealed a minor atrial septal defect (ASD) with shunting and a heterozygotic clotting factor V R506Q mutation. A remarkable blood eosinophilia of 9.80 E9/l (42%) together with fever, sinusitis, wide-spread bilateral nodular pulmonary infiltrates that did not respond to wide-spectrum antimicrobial treatment, positive anti-neutrophilic cytoplasmic antibodies, a high myeloperoxidase antibody level and slightly positive anti-proteinase 3 antibodies suggested the diagnosis of Churg-Strauss syndrome. These inflammatory symptoms and findings promptly responded to treatment with corticosteroids and cyclophosphamide. Conclusions: Even after the concomitant findings of the low risk factors, i.e. small ASD and heterozygotic clotting factor mutation, continued search for the final aetiology of stroke revealed Churg-Strauss syndrome, which was the key to the treatment.

Motor symptoms of Parkinson's disease (PD) can be relieved by deep brain stimulation (DBS). The mechanism of action of DBS is largely unclear. Magnetoencephalography (MEG) studies on DBS patients have been unfeasible because of strong magnetic artifacts. An artifact suppression method known as spatiotemporal signal space separation (tSSS) has mainly overcome these difficulties. We wanted to clarify whether tSSS enables noninvasive measurement of the modulation of cortical activity caused by DBS. We have studied auditory and somatosensory-evoked fields (AEFs and SEFs) of advanced PD patients with bilateral subthalamic nucleus (STN) DBS using MEG. AEFs were elicited by 1-kHz tones and SEFs by electrical pulses to the median nerve with DBS on and off. Data could be successfully acquired and analyzed from 12 out of 16 measured patients. The motor symptoms were significantly relieved by DBS, which clearly enhanced the ipsilateral auditory N100m responses in the right hemisphere. Contralateral N100m responses and somatosensory P60m responses also had a tendency to increase when bilateral DBS was on. MEG with tSSS offers a novel and powerful tool to investigate DBS modulation of the evoked cortical activity in PD with high temporal and spatial resolution. The results suggest that STN-DBS modulates auditory processing in advanced PD. Hum Brain Mapp, 2011. © 2010 Wiley-Liss, Inc.

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.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease with no effective therapy available. We recorded spontaneous magnetoencephalography and auditory evoked fields (AEFs) from a male patient with a rapidly progressive memory disorder, ataxia and myoclonus. Post-mortem examination confirmed sporadic CJD. Sources of the abnormal slow wave activity were localized with a beamformer software. Sources of sharp transients and AEFs were modeled with equivalent current dipoles. The estimated sources of spontaneous activity abnormalities were more dominant in the left hemisphere, in line with left-dominant abnormalities in diffusion-weighted MRI. Sources of AEFs were found in both temporal lobes. Magnetoencephalography measurements on CJD patients are feasible, and provide efficient means for localizing abnormal cortical activity in CJD.

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.

Scopolamine administration may be considered as a psychopharmacological model of Alzheimer’s disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD.

Corticokinematic coherence (CKC), i.e., coherence calculated between MEG and an accelerometer signal, recording movement kinematics, can be used for functional mapping of the sensorimotor cortex. Cortical sources of CKC, induced by both voluntary and passive movements, localize at the proximity of sensorimotor cortex. We tested the CKC during a static muscle contraction to compare it with simultaneously measured cortico-muscular coherence (CMC) estimated between MEG and surface EMG to study the role of postural tremor in CMC in ten healthy volunteers. CKC was detectable also during this static task. CKC and CMC spectra had similar power distributions, and sources of CMC and CKC colocalized at the cortex in close proximity of the central sulcus. During the static hold task, the accelerometer signal originates from the postural tremor. The similarities between CMC and CKC indicate that postural tremor is related to CMC in healthy subjects.

Deep brain stimulation (DBS) is an effective treatment method for motor symptoms of advanced Parkinson's disease. DBS-electrode is implanted to subthalamic nucleus to give precisely allocated electrical stimuli to brain. The optimal stimulus type has to be adjusted individually. Disease severity, main symptoms and biological factors play a role in correctly setting up the device. Currently there are no objective methods to assess the efficacy of DBS, hence the adjustment is based solely on clinical assessment. In optimal case an objectively measurable feature would point the right settings of DBS. Surface electromyographic and kinematic measurements have been used in Parkinson's disease research. As Parkinson's disease symptoms are known to change the EMG signal properties, these methods could be helpful aid in the clinical adjustment of DBS. In this study, 13 patients with advanced Parkinson's disease who received DBS treatment were measured. The patients were measured with seven different settings of the DBS in clinical range including changes in stimulation amplitude, frequency and pulse width. The EMG analysis was based on parameters that characterize EMG signal morphology. Correlation dimension and recurrence rate made the most significant difference in relation to optimal settings. In conclusion, EMG analysis is able to detect differences between the DBS setups, and can help in finding the correct parameters.

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.

Structural or operational synchrony analysis with EEG was conducted in order to detect functional interaction between cortical areas during an enhanced inhibition induced by the GABAergic agonist lorazepam in a double-blind, randomized, placebo-controlled, cross-over study in eight healthy human subjects. Specifically, we investigated whether a neuronal inhibitory system in the brain mediates functional decoupling of cortical areas. Single-dose lorazepam administration resulted in a widespread increase in the inter-area functional connectivity and an increase in the strength of functional long-range and interhemispheric connections. These results suggest that inhibition can be an efficient mechanism for synchronization of large neuronal populations.

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.

Background and Purpose— We sought to determine the recovery of cortical auditory discrimination in aphasic, left-hemisphere-stroke patients by using an electrophysiological response called mismatch negativity (MMN) and speech-comprehension tests. Methods— MMN in 8 left-hemisphere stroke patients was recorded in response to duration and frequency changes in a repetitive, harmonically rich tone 4 and 10 days and again 3 and 6 months after their first unilateral stroke. Eight age-matched, healthy persons served as control subjects. Results— At 4 days after stroke onset, patients’ sound discrimination was impaired in their left hemisphere, as suggested by attenuated MMNs, especially to right-ear stimuli. At 3 months after stroke, however, MMN to the right-ear duration change had significantly increased and was of normal size. A significant change for the frequency MMN was found for left-ear stimuli between 3 and 6 months after stroke. During the follow-up period, progressive improvement in speech-comprehension tests was also observed. Furthermore, there was a significant correlation between the change in the duration MMN amplitude and the Boston Diagnostic Aphasia Examination speech-comprehension test from 10 days to 3 months after stroke. Conclusions— These results suggest that the MMN can be used as an index of the recovery of auditory discrimination.

Auditory P50 and N100 responses reflect preattentive processing, whereas subsequent mismatch negativity (MMN) response indexes memory-based comparison process. Divergent ERP responses have been found in schizophrenia and in Parkinson's disease (PD), which have abnormalities in cerebral dopamine activity. We used simultaneously magnetoencephalography and electroencephalography to investigate, whether a single dose of haloperidol, a dopamine D2-receptor antagonist, modulates preattentive auditory processing using a randomized, double-blind, placebo-controlled crossover design. Our results showed that haloperidol did not alter MMN to frequency and duration changes, whereas the magnetic MMN to frequency change was significantly accelerated. The amplitude and latency changes of the electric and magnetic P50 and N100 were insignificant. Our results indicate that memory-based sound comparison and preceding cortical processing underlying stimulus detection are not attenuated by haloperidol, whereas haloperidol appears to accelerate preattentive sound comparison.

Background Continuous levodopa-carbidopa intestinal gel (LCIG) diminishes daily “off” time and dyskinesia in patients with advanced Parkinson′s disease (PD). Complications are common with percutaneous endoscopic gastrostomy with a jejunal extension tube (PEG-J). Aim of the Study To report the clinical outcome of LCIG in patients with advanced PD in the years 2006–2014 at Helsinki University Hospital. Patients and Methods Levodopa-carbidopa intestinal gel treatment started following PEG-J placement in patients with advanced PD after successful in-hospital LCIG trial with a nasojejunal tube. Demographics, PEG-J procedures, discontinuation of LCIG, complications and mortality were retrospectively analyzed. Results [mean (SD)] Sixty patients with advanced PD [age 68(7) years; duration of PD: 11(4) years] had LCIG treatment for 26(23) months. The majority of patients with advanced PD were satisfied with the LCIG treatment. For 51 patients (85%), the pump was on for 16 hr a day, and for nine patients (15%) it was on for 24 hr a day. After 6 months, the levodopa-equivalent daily dose (LEDD) had increased by 30% compared to pre-LCIG LEDD. Sixty patients underwent a total of 156 PEG-J procedures, and 48 patients (80%) had a total of 143 complications. Forty-six patients (77%) had 119 PEG-J or peristomal complications, and 22 patients (37%) had a total of 25 other complications. The most common complications were accidental removal of the J-tube in 23 patients (38%) and ≥5% weight loss in 18 patients (30%). Fifteen patients discontinued the LCIG after 21 (21) months. At the end of the follow-up period of 33(27) months, 38 patients were still on LCIG and nine (15%) had died. Conclusion Most patients were satisfied with LCIG treatment. A few patients lost weight whereas the majority had complications with PEG-J. When LCIG treatment is carried out, neurological and endoscopic units must be prepared for multiple endoscopic procedures.

Syphilis is an infectious disease caused by Treponema pallidum. We describe two patients with chronic syphilis causing neurosyphilis. The first had had several brain infarctions due to the presence of meningovascular syphilis. Second patient suffered from motor and psychiatric symptoms caused by syphilis. The symptoms of our patients were alleviated by antibiotic therapy. Recognition of the multifaceted symptom picture of syphilis is increasingly important, because the occurrence of the disease has increased in our country over the last few decades. An early enough treatment can prevent permanent disability of the patient.

We used 122-channel magnetoencephalography (MEG) and 64-channel electroencephalogrphy (EEG) simultaneously to study the effects of dopaminergic transmission on human selective attention in a randomized, double-blind placebo-controlled cross-over design. A single dose of dopamine D2 receptor antagonist haloperidol (2 mg) or placebo was given orally to 12 right-handed healthy volunteers 3 hours before measurement. In a dichotic selective attention task, subjects were presented with two trains of standard (700 Hz to the left ear, 1,100 Hz to the right ear) and deviant (770 and 1,210 Hz, respectively) tones. Subjects were instructed to count the tones presented to one ear; whereas, the tones presented to the other ear were to be ignored. Haloperidol significantly attenuated processing negativity (PN), an event-related potential (ERP) component elicited by selectively attended standard tones at 300-500 ms after stimulus presentation. These results, indicating impaired selective attention by a blockade of dopamine D2 receptors, were further accompanied with increased mismatch negativity (MMN), elicited by involuntary detection of task-irrelevant deviants. Taken together, haloperidol seemed to induce functional changes in neural networks accounting for both selective and involuntary attention, suggesting modulation of these functions by dopamine D2 receptors.

The ability of left-hemisphere stroke patients (n = 8) and healthy control subjects (n = 8) to process sounds preattentively and attentively was studied by recording auditory event-related potentials (ERPs) and behavioral responses. For the right-ear stimulation, the mismatch negativity (MMN) was significantly smaller in the patients than control subjects over both hemispheres. For the left-ear stimuli, the MMN was significantly smaller in the patient group than in the control group over the left hemisphere, whereas no group differences were obtained over the right hemisphere. In addition, the N1 amplitude was reduced bilaterally for the right-ear stimulation (with the reduction being larger over the left hemisphere), whereas no significant effects on the N1 amplitude were found for the left-ear stimulation. Behaviorally, the patients detected significantly fewer deviant tones than did the control subjects irrespective of the stimulated ear. The present results thus suggest that the long-latency ERPs can be used to probe such auditory processing deficits that are difficult to define with behavioral measures. Especially by recording MMN to monaural stimuli, the discrimination accuracy can be separately determined for the left and right temporal lobes.

Aging attenuates automatic auditory discrimination to duration change, whereas frequency change detection is relatively unimpaired in aging and in Alzheimer's disease (AD). Here we studied with a whole-head magnetometer whether cortical auditory discrimination to duration change as shown by magnetic mismatch negativity (MMNm) response is impaired in AD. Twenty AD patients with mild to moderate cognitive impairment and 18 age-matched healthy subjects were monaurally presented a sequence of frequent standard tones embedded with occasional deviants with shorter duration. MMNm was significantly delayed in the left hemisphere ipsilaterally to the ear stimulated in the patient group, whereas the MMNm amplitudes over both hemispheres were quite similar in both groups. This suggests that although MMNm is delayed in the left hemisphere, the automatic discrimination to duration change in the auditory cortex is not attenuated in the early stages of AD.

Acetylcholine (ACh) is a potent neuromodulator in the brain with multiple, complex effects on neuronal function, most of which are mediated by muscarinic receptors. Generally, the most significant effect is excitation of pyramidal neurones and facilitation of responses to afferent stimulation. Much of the information on the ACh effects comes from studies utilizing in vitro or anesthetized in vivo preparations, while fewer data are available from awake animals or humans. We studied human somatosensory evoked magnetic fields (SEFs), which reflect summated postsynaptic currents in pyramidal neurones in area 3b, and in the opercular somatosensory cortex, when cholinergic transmission was modulated either by a central (scopolamine, 0.3 mg, i.v.) or peripheral (glycopyrrolate, 0.2 mg, i.v.) muscarinic antagonist. A randomized, double-blind, cross-over design was employed. SEFs were elicited by right median nerve stimulation at the wrist with constant-current pulses above motor threshold. The first excitatory cortical response from area 3b (N20m) was not affected by the central muscarinic blockade, while later P35m and P60m deflections were significantly reduced. The responses from the opercular somatosensory cortex showed some tendency toward reduction, but no significant alterations. The results show that somatosensory cortical processing can be modulated by muscarinic transmission at a relatively early stage. Relative membrane hyperpolarization of pyramidal neurons due to scopolamine (caused by blocking an ACh-induced tonic depolarization) is discussed as a possible mechanism underlying the observed effects.

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.

Simultaneous auditory processing between the hemispheres was studied with a whole-head magnetometer in 13 abstinent chronic alcoholics and 10 healthy control subjects. Auditory stimuli were presented monaurally with interstimulus intervals of 0.5 and 2.5 sec in different blocks. The N100m response, which contributes to stimulus detection, was significantly accelerated in the hemisphere ipsilateral to the ear stimulated in abstinent alcoholics. The MMNm response reflecting automatic stimulus-change detection peaked earlier in alcoholics, and the ipsilateral N100m latency correlated significantly with the abstinence duration. These results suggest that auditory processing is accelerated in the auditory cortex ipsilateral to the stimulated ear in chronic abstinent alcoholics and that the accelerated processing is at least partly reversible. This may be caused by the hyperexcitation in the brain related to the ethanol withdrawal.

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.

Whole-head magnetoencephalographic (MEG) responses to repeating standard tones and to infrequent slightly higher deviant tones and complex novel sounds were recorded together with event-related brain potentials (ERPs). Deviant tones and novel sounds elicited the mismatch negativity (MMN) component of the ERP and its MEG counterpart (MMNm) both when the auditory stimuli were attended to and when they were ignored. MMNm generators were located bilateral to the superior planes of the temporal lobes where preattentive auditory discrimination appears to occur. A subsequent positive P3a component was elicited by deviant tones and with a larger amplitude by novel sounds even when the sounds were to be ignored. Source localization for the MEG counterpart of P3a (P3am) suggested that the auditory cortex in the superior temporal plane is involved in the neural network of involuntary attention switching to changes in the acoustic environment.

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.

Deep brain stimulation (DBS) has been used for treatment of advanced Parkinson's disease (PD) since 1990's. Duodenal levodopa infusion (DLI) has been available since 2006.Patient records of DLI patients and clinical data of DBS patients from 2006-2010 were requested from all university and central hospitals in Finland.DLI was tested on 105 patients. 84 had a favourable response and were on long-term treatment. 85 patients underwent DBS operation. Technical problems and complications were common in DLI treated patients.DLI has become as popular as DBS in the treatment of advanced PD, but has a quite high complication rate.

Objective Parkinsonian patients have abnormal oscillatory activity within the basal ganglia-thalamocortical circuitry. Particularly, excessive beta band oscillations are thought to be associated with akinesia. We studied whether cortical spontaneous activity is modified by deep brain stimulation (DBS) in advanced Parkinson’s disease and if the modifications are related to the clinical symptoms. Methods We studied the effects of bilateral electrical stimulation of subthalamic nucleus (STN) on cortical spontaneous activity by magnetoencephalography (MEG) in 11 Parkinsonian patients. The artifacts produced by DBS were suppressed by tSSS algorithm. Results During DBS, UPDRS (Unified Parkinson’s Disease Rating Scale) rigidity scores correlated with 6–10 Hz and 12–20 Hz somatomotor source strengths when eyes were open. When DBS was off UPDRS action tremor scores correlated with pericentral 6–10 Hz and 21–30 Hz and occipital alpha source strengths when eyes open. Occipital alpha strength decreased during DBS when eyes closed. The peak frequency of occipital alpha rhythm correlated negatively with total UPDRS motor scores and with rigidity subscores, when eyes closed. Conclusion STN DBS modulates brain oscillations both in alpha and beta bands and these oscillations reflect the clinical condition during DBS. Significance MEG combined with an appropriate artifact rejection method enables studies of DBS effects in Parkinson’s disease and presumably also in the other emerging DBS indications.

Alzheimer's Disease (AD) is the most common dementia in the elderly and is estimated to affect tens of millions of people worldwide. AD is believed to have a prodromal stage lasting ten or more years. While amyloid deposits, tau filaments, and loss of brain cells are characteristics of the disease, the loss of dendritic spines and of synapses predate such changes. Popular preclinical detection strategies mainly involve cerebrospinal fluid biomarkers, magnetic resonance imaging, metabolic PET scans, and amyloid imaging. One strategy missing from this list involves neurophysiological measures, which might be more sensitive to detect alterations in brain function. The Magnetoencephalography International Consortium of Alzheimer's Disease arose out of the need to advance the use of Magnetoencephalography (MEG), as a tool in AD and pre-AD research. This paper presents a framework for using MEG in dementia research, and for short-term research priorities. Copyright © 2011 Edward Zamrini et al.

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.

Following the diagnosis of Parkinson's disease, treatment may be initiated with MAO-B-inhibitor, even prior to the development of any functional deficit. For patients with a functional deficit who are younger (usually under 75 years of age) and otherwise in good condition, treatment should be started with a dopamine agonist or MAO-B-inhibitor. In other patients, initial treatment with levodopa is recommended. In the case of difficult on-off-symptoms and dyskinesias in spite of optimal treatment, surgical procedures and duodenal levodopa infusion should be considered. Rehabilitation should be targeted at specific problems associated with functional skills.

Creutzfeldt-Jakob Disease (CJD) is a rare neurodegenerative disease, which belongs to a group of spongiform encephalopathies termed prion diseases.