Abnormal Oscillatory Activity Research Articles

Failure to suppress low-frequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for the motor symptoms of Parkinson's disease (PD). However, the mechanisms of action of DBS are unknown. Random temporal patterns of DBS are less effective than regular DBS, but the neuronal basis for this dependence on temporal pattern of stimulation is unclear. Using a rat model of PD, we quantified the changes in behavior and single-unit activity in globus pallidus externa and substantia nigra pars reticulata during high-frequency STN DBS with different degrees of irregularity. Although all stimulus trains had the same average rate, 130-Hz regular DBS more effectively reversed motor symptoms, including circling and akinesia, than 130-Hz irregular DBS. A mixture of excitatory and inhibitory neuronal responses was present during all stimulation patterns, and mean firing rate did not change during DBS. Low-frequency (7-10 Hz) oscillations of single-unit firing times present in hemiparkinsonian rats were suppressed by regular DBS, and neuronal firing patterns were entrained to 130 Hz. Irregular patterns of DBS less effectively suppressed 7- to 10-Hz oscillations and did not regularize firing patterns. Random DBS resulted in a larger proportion of neuron pairs with increased coherence at 7-10 Hz compared with regular 130-Hz DBS, which suggested that long pauses (interpulse interval >50 ms) during random DBS facilitated abnormal low-frequency oscillations in the basal ganglia. These results suggest that the efficacy of high-frequency DBS stems from its ability to regularize patterns of neuronal firing and thereby suppress abnormal oscillatory neural activity within the basal ganglia.

Intraoperative electrocorticography for physiological research in movement disorders: principles and experience in 200 cases.

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via "broadband gamma" (50-200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board-approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.

Effects of NMDA receptor antagonists and antipsychotics on high frequency oscillations recorded in the nucleus accumbens of freely moving mice.

RationaleAbnormal oscillatory activity associated with N-methyl-D-aspartate (NMDA) receptor hypofunction is widely considered to contribute to the symptoms of schizophrenia.ObjectiveThis study aims to characterise the changes produced by NMDA receptor antagonists and antipsychotics on accumbal high-frequency oscillations (HFO; 130–180 Hz) in mice.MethodsLocal field potentials were recorded from the nucleus accumbens of freely moving mice.ResultsSystemic injection of ketamine and MK801 both dose-dependently increased the power of HFO and produced small increases in HFO frequency. The atypical antipsychotic drug, clozapine, produced a robust dose-dependent reduction in the frequency of MK801-enhanced HFO, whilst haloperidol, a typical antipsychotic drug, had little effect. Stimulation of NMDA receptors (directly or through the glycine site) as well as activation of 5-HT1A receptors, reduced the frequency of MK801-enhanced HFO, but other receptors known to be targets for clozapine, namely 5-HT2A, 5-HT7 and histamine H3 receptors had no effect.ConclusionsNMDA receptor antagonists and antipsychotics produce broadly similar fundamental effects on HFO, as reported previously for rats, but we did observe several notable differences. In mice, HFO at baseline were weak or not detectable unlike rats. Post-injection of NMDA receptor antagonists HFO was also weaker but significantly faster. Additionally, we found that atypical antipsychotic drugs may reduce the frequency of HFO by interacting with NMDA and/or 5-HT1A receptors.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-015-4073-0) contains supplementary material, which is available to authorized users.

Periodic oscillatory myoelectrical activity in the gut

Introduction: Myoelectrical (ME) activity, including slow waves and spikes, modulate a variety of patterns of intestinal motility. Any abnormality in the generation and propagation of migrating ME complexes leads to uncoordinated contractions of smooth muscle syncytia, responsible for a clinical condition classified as intestinal dysrhythmia. Objectives: To investigate the dynamics of myoelectrical patterns in the wall of the small bowel under normal and pathological conditions. Materials and methods: The study applied a computer model to analyse electromechanical wave phenomena in a functional unit of the gut. The computer model was based on anatomical and physiological data obtained from in vivo and in vitro experiments. During the numerical experiments the spatial distribution and the dynamics of ME patterns, frequencies, velocities and active forces were recorded. Results: Results of numerical experiments revealed periodic oscillatory activity in the longitudinal smooth muscle layer of the organ. This depended on pacemaker settings and intrinsic electrical properties of muscle syncytia. The observed self-sustained ME activity might underlie the pathogenesis of intestinal dysrhythmia. Conclusions: A detailed explanation for the observed event cannot be provided at present. We suggest that the abnormal oscillatory activity of interstitial cells of Cajal and histomorphological arrangements among muscle cells contribute to the outcome. Acknowledgements: Arabian Gulf University for sponsoring the research.

Compensating for thalamocortical synaptic loss in Alzheimer's disease.

The study presents a thalamocortical network model which oscillates within the alpha frequency band (8–13 Hz) as recorded in the wakeful relaxed state with closed eyes to study the neural causes of abnormal oscillatory activity in Alzheimer's disease (AD). Incorporated within the model are various types of cortical excitatory and inhibitory neurons, recurrently connected to thalamic and reticular thalamic regions with the ratios and distances derived from the mammalian thalamocortical system. The model is utilized to study the impacts of four types of connectivity loss on the model's spectral dynamics. The study focuses on investigating degeneration of corticocortical, thalamocortical, corticothalamic, and corticoreticular couplings, with an emphasis on the influence of each modeled case on the spectral output of the model. Synaptic compensation has been included in each model to examine the interplay between synaptic deletion and compensation mechanisms, and the oscillatory activity of the network. The results of power spectra and event related desynchronization/synchronization (ERD/S) analyses show that the dynamics of the thalamic and cortical oscillations are significantly influenced by corticocortical synaptic loss. Interestingly, the patterns of changes in thalamic spectral activity are correlated with those in the cortical model. Similarly, the thalamic oscillatory activity is diminished after partial corticothalamic denervation. The results suggest that thalamic atrophy is a secondary pathology to cortical shrinkage in Alzheimer's disease. In addition, this study finds that the inhibition from neurons in the thalamic reticular nucleus (RTN) to thalamic relay (TCR) neurons plays a key role in regulating thalamic oscillations; disinhibition disrupts thalamic oscillatory activity even though TCR neurons are more depolarized after being released from RTN inhibition. This study provides information that can be explored experimentally to further our understanding on the neurodegeneration associated with AD pathology.

Cerebellar influence on motor cortex plasticity: behavioral implications for Parkinson's disease.

Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other’s plastic responses and functions. The defective striatal signaling in Parkinson’s disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD.

Abnormal patterns of theta frequency oscillations during the temporal evolution of freezing of gait in Parkinson’s disease

ObjectiveWe sought to characterize the electrophysiological signature of Freezing of gait in Parkinson’s disease. MethodsWe examined 24 patients with idiopathic Parkinson’s disease and significant freezing of gait as they performed a series of timed up-and-go tasks in their ‘off’ state while electroencephalographic data was collected from four scalp leads. Fast Fourier Transformation was utilized to explore the power spectral density between periods of normal walking and periods of freezing, as well as during the transition between the two states. In addition, Cross Spectrum and Cross Frequency analyses were used to explore the role of impaired temporal and spatial connectivity. ResultsWhen compared to walking, episodes of freezing were associated with a significant increase in theta band power within the central and frontal leads. The transition from normal walking to freezing of gait was also associated with increased theta frequency coupling between the central and frontal leads, along with an increase in cross-frequency coupling in the central lead. ConclusionsEpisodes of freezing of gait in Parkinson’s disease are associated with abnormal oscillatory activity in the brain. SignificanceThese results provide novel insights into the pattern of spatiotemporal dynamics underlying freezing of gait and may provide a potential means for therapeutic prediction and alleviation of freezing episodes in susceptible patients.

P 252. A double blind, placebo controlled exploration of the effect of repeated sessions of transcranial alternating current stimulation on tinnitus loudness and distress

A number of recent studies have assessed a neurological basis for tinnitus in the form of abnormal oscillatory activity in the auditory cortex a network of limbic and other brain areas. We sought to modify such activity using alternating current stimulation at different rates in a double blind placebo controlled investigation. The data show a chronic effect of alpha range stimulation (but not low gamma) at temporal lobe electrode sites on both tinnitus intensity and distress. The data can be interpreted in terms of a disruption of the balance between alpha and high gamma activity.

Abnormal MEG oscillatory activity during visual processing in the prefrontal cortices and frontal eye-fields of the aging HIV brain.

Shortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation. High-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming. Uninfected controls had increased neuronal synchronization in the 6-12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions. MEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health.

Antipsychotic compounds differentially modulate high-frequency oscillations in the rat nucleus accumbens: a comparison of first- and second-generation drugs

Improved understanding of the actions of antipsychotic compounds is critical for a better treatment of schizophrenia. Abnormal oscillatory activity has been found in schizophrenia and in rat models of the disease. N-Methyl-D-aspartic acid receptor (NMDAR) antagonists, used to model certain features of schizophrenia, increase the frequency and power of high-frequency oscillations (HFO, 130-180 Hz) in the rat nucleus accumbens, a brain region implicated in schizophrenia pathology. Antipsychotics can be classified as first- and second-generation drugs, the latter often reported to have wider benefit in humans and experimental models. This prompted the authors to examine the pre- and post-treatment effects of clozapine, risperidone (second-generation drugs) and sulpiride and haloperidol (first-generation drugs) on ketamine and MK801-enhanced accumbal HFO. Both NMDAR antagonists increased HFO frequency. In contrast, clozapine and risperidone markedly and dose-dependently reduced the frequency of spontaneous and NMDAR-antagonist-enhanced HFO, whilst a moderate effect was found for sulpiride and a much weaker effect for haloperidol. Unexpectedly, we found reductions in HFO frequency were associated with an increase in its power. These findings indicate that modulation of accumbal HFO frequency may be a fundamental effect produced by antipsychotic compounds. Of the drugs investigated, first- and second-generation compounds could be dissociated by their potency on this measure. This effect may partially explain the differences in the clinical profile of these drugs.

Beta band stability over time correlates with Parkinsonian rigidity and bradykinesia

Abnormal oscillatory activity in the basal ganglia is increasingly implicated in the pathophysiology of Parkinson's disease. Such activity is recorded in patients in the form of oscillations in the local field potential (LFP) picked up in the subthalamic nucleus. Previous studies have focused on correlations between features of the time averaged power or amplitude spectrum of the LFP and the clinical state, either off medication or in response to levodopa. However, average spectral densities do not take account of time variant spectral properties and we hypothesised that these dynamic properties of the spectrum of the LFP would contain additional information about clinical state. Here we assess the variability in LFP amplitude over time using the coefficient of variation (CV), evaluating this with regard to clinical state off medication and in response to levodopa in two datasets. The CV of activity in the high beta frequency band was found to be correlated with clinical state off levodopa (rho=−0.59, p<0.001) and this was shown to be complementary, rather than redundant, to spectral amplitude in a multiple regression analysis, selective for rigidity–bradykinesia and highly focal. Similarly, a strong correlation was found between change in clinical scores and change in high beta CV following levodopa (rho=−0.66, p=0.004). This too was selective for rigidity–bradykinesia and non-redundant to spectral power in a multiple regression model. Our results indicate that temporal stability in the beta band is correlated with rigidity–bradykinesia. It is suggested that loss of beta reactivity is deleterious to basal ganglia function over and above any concomitant change in absolute level of beta synchrony. The CV of LFP beta band amplitude may potentially provide an additional index of clinical state suitable for feedback control in closed loop stimulation therapy.

Somatomotor mu rhythm amplitude correlates with rigidity during deep brain stimulation in Parkinsonian patients

ObjectiveParkinsonian 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. MethodsWe 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. ResultsDuring DBS, UPDRS (Unified Parkinson’s Disease Rating Scale) rigidity scores correlated with 6–10Hz and 12–20Hz somatomotor source strengths when eyes were open. When DBS was off UPDRS action tremor scores correlated with pericentral 6–10Hz and 21–30Hz 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. ConclusionSTN DBS modulates brain oscillations both in alpha and beta bands and these oscillations reflect the clinical condition during DBS. SignificanceMEG 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.

Maturation of EEG oscillations in children with sodium channel mutations

Dravet syndrome (DS) is a severe epileptic encephalopathy beginning in infancy in which children have difficult to control seizures and cognitive impairment. The majority of children with DS carry mutations of the gene Scn1a, which codes for the alpha subunit of the type 1 voltage-gated sodium channel and is important for the function of interneurons. Interneurons have a critical role in the generation of brain rhythms involved in cognitive processing. We hypothesized that children with DS with Scn1a mutations would have abnormal oscillatory activity. To address this hypothesis, we used EEG power spectral analysis during the wakening to determine if frequency and power are altered in 23 EEGs from 12 children with DS compared to 18 age-matched controls. While there were few differences between the EEG power spectra in DS and controls in children under 2years, in older children group differences were apparent. In DS children between 3 and 5years there were significant decreases in percentage of alpha power compared to controls and in DS children over age 6years there was a marked increase of theta and decrease of alpha compared to controls. Developmental status paralleled the power spectral analysis with an increasing likelihood of having severe cognitive problems with increasing age. These results demonstrate that Scn1a mutations result in an age-dependent alteration in oscillatory process. Such abnormalities in developmental progression of oscillations may play an important role in poor cognitive development in children with DS.

Altered directional connectivity in Parkinson's disease during performance of a visually guided task

Recent animal studies have suggested that cortical areas may play a greater role in the modulation of abnormal oscillatory activity in Parkinson's disease (PD) than previously recognized. We investigated task and medication-dependent, EEG-based directional cortical connectivity in the θ (4–7Hz), α (8–12Hz), β (13–30Hz) and low γ (31–50Hz) frequency bands in 10 PD subjects and 10 age-matched controls. All subjects performed a visually guided task previously shown to modulate abnormal oscillatory activity in PD subjects. We examined the connectivity in the simultaneously-recorded EEG between 5 electrode regions of interest (fronto-central, left and right sensorimotor, central and occipital) using a sparse, multivariate, autoregressive-based partial directed coherence method. For comparison, we utilized traditional Fourier analysis to evaluate task-dependent frequency spectra modulation in these same regions. While the spectral analysis revealed some overall differences between PD and control subjects, it demonstrated relatively modest changes between regions. In contrast, the partial directed coherence-based analysis revealed multifaceted, regionally and directionally-dependent alterations of connectivity in PD subjects during both movement preparation and execution. Connectivity was particularly altered posteriorly, suggesting abnormalities in visual and visuo-motor processing in PD. Moreover, connectivity measures in the α, β and low γ frequency ranges correlated with motor Unified Parkinson's Disease Rating Scores in PD subjects withdrawn from medication. Levodopa administration only partially restored connectivity, and in some cases resulted in further exacerbation of abnormalities. Our results support the notion that PD is associated with significant alterations in connectivity between brain regions, and that these changes can be non-invasively detected in the EEG using partial directed coherence methods. Thus, the role of EEG to monitor PD may need to be further expanded.

High frequency oscillations in the subthalamic nucleus: A neurophysiological marker of the motor state in Parkinson's disease

Increasing evidence suggests that abnormal oscillatory activity in basal ganglia and cortex plays a pivotal role in the pathophysiology of Parkinson's disease. Recordings of local field potentials from subthalamic nucleus of patients undergoing deep brain stimulation have focused on oscillations occurring at frequencies below 100 Hz in the alpha, beta and gamma range and suggested that, in particular, an increase of beta band oscillations underlies slowing of movement in Parkinson's disease. Recent findings showing that the amplitude of high frequency oscillations (> 200 Hz) couples with the phase of beta activity have raised the important question about the role of subthalamic high frequency oscillations in Parkinson's disease. To investigate functional characteristics and clinical relevance of high frequency oscillations, we recorded local field potentials from 18 subthalamic nuclei of 9 akinetic-rigid Parkinsonian patients with implanted deep brain stimulation electrodes and still externalised leads before and after intake of levodopa. We identified two distinct bands of high frequency oscillations, one centred around 250 Hz and another one around 350 Hz that show characteristic levodopa dependent amplitude and coupling behaviours. Administration of levodopa changed the power ratio between the two high frequency bands towards the component centred around 350 Hz in all 18 nuclei under study (p < 10 − 4 ). Moreover, this power ratio correlated significantly with the Unified Parkinson's Disease Rating Scale hemibody akinesia/rigidity subscore (r = 0.3618, p = 0.015), but interestingly not with beta peak power (p = 0.1) suggesting that levodopa induced changes in high frequency and beta oscillations are at least potentially independent of each other. Accordingly, a combined parameter composed of power ratio of high frequency oscillations and beta peak power significantly increased the correlation with the motor state (r = 0.45, p = 0.004). These results indicate that a shift from slower to faster frequencies of the spectrum greater than 200 Hz represents a prokinetic neurophysiological marker underlying levodopa induced motor improvement in Parkinson's disease.

P16-2 Abnormal cortical oscillatory activity in schizophrenia-like psychosis of epilepsy after resection of meningioma

P16-2 Abnormal cortical oscillatory activity in schizophrenia-like psychosis of epilepsy after resection of meningioma

Use of magnetoencephalography (MEG) to study functional brain networks in neurodegenerative disorders

The pathophysiological mechanisms underlying clinical symptoms in neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD) are incompletely understood. Magnetoencephalography (MEG) is a relatively new functional neuroimaging technique, which allows the simultaneous recording of the brain's magnetic activity from large arrays of sensors covering the whole head. MEG studies in PD and AD have identified characteristic patterns of abnormal oscillatory activity in different frequency bands. Furthermore, MEG studies aimed at the characterization of distributed functional networks have demonstrated distinct patterns of abnormal connectivity in demented and non-demented PD, as well as in AD. In PD abnormal oscillatory activity and disturbed connectivity may respond differently to dopaminergic treatment. Further studies in this field could benefit from new technological developments such as ultra low field MRI and from the application of a well-defined theoretical framework such as graph theory to the study of disturbed brain networks.

Local injection of MK801 modifies oscillatory activity in the nucleus accumbens in awake rats

Pharmacological blockade of NMDA receptors is used to model certain aspects of schizophrenia. It had been shown previously that ketamine dose dependently enhances high-frequency oscillations in the rodent nucleus accumbens, a structure implicated in schizophrenia. Here, the authors examined the effect of intra-accumbal and systemic administration of MK801 on delta, gamma and high-frequency oscillatory activity recorded in the nucleus accumbens of freely moving rats. In this study, rats were implanted with electrodes in the nucleus accumbens for chronic local field potential recording. Rats received either bilateral injections of MK801 (1 and 4 microg) or intraperitoneal injections of the drug (0.1 and 0.5 mg/kg). Saline was used as control in each instance. Both local and systemic injections significantly enhanced the power and frequency of high-frequency oscillations and caused an increase in the occurrence, duration and amplitude of high-frequency oscillatory bursts. In contrast, no effect or a decrease in the power of delta and gamma bands was observed following local or systemic administration of MK801, respectively. These findings suggest that the dominant change in oscillatory activity after administration of NMDA receptor antagonists affect high frequencies. Moreover, direct NMDA blockade in the accumbal circuitry is sufficient to generate increases in high-frequency oscillations. The presence of abnormal oscillatory activity in the accumbens may be associated with the psychomimetic effects of NMDA receptor antagonists.

Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: Preliminary observations

Orthostatic tremor (OT) is a disabling movement disorder associated with postural and gait impairment in the elderly. Medical therapy often yields insufficient benefit. We report the clinical and electrophysiological data on two patients with medication-refractory OT treated with deep brain stimulation of the ventral intermediate thalamic nucleus (Vim DBS). Patient 1 underwent bilateral deep brain stimulation (DBS) and Patient 2 unilateral Vim DBS following 28 and 30 years of disease duration, respectively. Both patients showed increased latency to symptom onset after rising from a seated position, improved tolerance for prolonged standing, and slower crescendo of tremor severity when remaining upright. Postoperative evaluation demonstrated decreased amplitude of electromyographic activity with persistence of well-defined oscillatory behavior showing strong coherence at 15 Hz between all muscles tested in the upper and lower limbs. Postural sway was unchanged. Clinical benefits have been sustained for over 18 months in Patient 1, and receded after 3 months in Patient 2. These findings support the consideration of bilateral Vim DBS implantation as a therapeutic option in patients with medically refractory OT. Further efficacy studies on chronic stimulation to disrupt the abnormal oscillatory activity in this disorder are warranted.

P1-388: Resting-state oscillatory brain dynamics in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia, nevertheless it lacks a definitive antemortem diagnostic test. Altered resting-state oscillatory brain activity may reflect underlying neuropathological changes, and its characterization may lead to new diagnostic possibilities. Due to its superior temporal and spatial resolution compared to EEG, magnetoencephalography (MEG) is a promising technique for this purpose. The present study using MEG and spectral analysis was set up to study differences in relative power of oscillatory brain activity in ten distinct cortical regions. Whole-head 151-channel MEG was recorded in 18 AD patients (mean age 72.1 years, SD 5.6; 7 females; mean MMSE 19.2, range: 13–25) and 18 healthy controls (mean age 69.1, SD 6.8, 11 females; mean MMSE 29, range: 27–30) during a no-task eyes-closed resting state. MEG channels were grouped in ten distinct cerebral regions (central, frontal, occipital, parietal and temporal; both left and right), and relative power was calculated using the Fast Fourier Transformation. The analysis was done both globally and for the specific regions separately, for the delta (0.5–4 Hz), theta (4–8 Hz), alpha1 (8–10 Hz), alpha2 (10–13 Hz), beta (13–30 Hz), and the gamma (30–50 Hz) frequency band. Relative power analysis showed a widespread slowing of oscillatory brain activity, with significant differences in the delta, alpha1, alpha2 and beta frequency bands, particularly in the temporo-parietal regions. Greatest diagnostic accuracy was found in the beta band, especially in the right occipital area (sensitivity 94%, specificity 78%). Correlations of relative power and MMSE scores were generally weak, but with a positive trend in the alfa1 band (R=0.53). Resting-state oscillatory brain activity is different in Alzheimer's disease. Our findings confirm the well-known slowing of brain activity, and show that widespread regional differences between AD and healthy controls can be found using MEG and standard spectral analysis techniques. By analyzing specific cortical regions, this study gives a more detailed topographical view of abnormal oscillatory activity in AD, which may eventually contribute to a more definitive diagnosis in AD.