L.J. Bour

Directional Recording of Subthalamic Spectral Power Densities in Parkinson's Disease and the Effect of Steering Deep Brain Stimulation

BACKGROUNDnA new 32-contacts deep brain stimulation (DBS) lead, capable of directionally steering stimulation, was tested intraoperatively.nnnOBJECTIVEnThe aim of this pilot study was to perform recordings from the multidirectional contacts and to investigate the effect of directional current steering on the local field potentials (LFPs).nnnMETHODSnIn eight patients with Parkinsons disease, after standard microelectrode recording and clinical testing, the new lead was temporarily implanted. The 32-channel LFP recordings were measured simultaneously at different depths and directions before and after directional stimulation.nnnRESULTSnThe spatial distribution of LFPs power spectral densities across the contact array at baseline marked the borders of the subthalamic nucleus (STN) with a significant increase in beta power and with a mean accuracy of approximately 0.6xa0mm in four patients.The power in the 18.5-30xa0Hz frequency band varied across different directions in all patients. In the three cases that showed improvement of rigidity, this was higher when current was steered toward the direction with the highest LFP power in the beta band. Subthalamic LFPs in six patients showed a differential frequency-dependent suppression/enhancement of the oscillatory activity in the 10-45xa0Hz frequency band after four different steering modes as compared to ring mode, suggesting a higher specificity.nnnCONCLUSIONSnThrough a new 32-contact DBS lead it is possible to record simultaneous subthalamic LFPs at different depths and directions, providing confirmation of adequate lead placement and multidirectional spatial-temporal information potentially related to pathological subthalamic electrical activity and to the effect of stimulation. Although further research is needed, this may improve the efficiency of steering stimulation.

Functional neuronal activity and connectivity within the subthalamic nucleus in Parkinson’s disease

OBJECTIVEnCharacterization of the functional neuronal activity and connectivity within the subthalamic nucleus (STN) in patients with Parkinsons disease (PD).nnnMETHODSnSingle units were extracted from micro-electrode recording (MER) of 18 PD patients who underwent STN deep brain stimulation (DBS) surgery. The firing rate and pattern of simultaneously recorded spike trains and their coherence were analyzed. To provide a precise functional assignment of position to the observed activities, for each patient we mapped its classified multichannel STN MERs to a generic atlas representation with a sensorimotor part and a remaining part.nnnRESULTSnWithin the sensorimotor part we found significantly higher mean firing rate (P < 0.05) and significantly more burst-like activity (P < 0.05) than within the remaining part. The proportion of significant coherence in the beta band (13-30 Hz) is significantly higher in the sensorimotor part of the STN than elsewhere (P = 0.015).nnnCONCLUSIONSnThe STN sensorimotor part distinguishes itself from the remaining part with respect to beta coherence, firing rate and burst-like activity and postoperatively was found as the preferred target area.nnnSIGNIFICANCEnOur firing behavior analysis may help to discriminate the STN sensorimotor part for the placement of the DBS electrode.

From Parkinsonian thalamic activity to restoring thalamic relay using deep brain stimulation: new insights from computational modeling.

We present a computational model of a thalamocortical relay neuron for exploring basal ganglia thalamocortical loop behavior in relation to Parkinsons disease and deep brain stimulation (DBS). Previous microelectrode, single-unit recording studies demonstrated that oscillatory interaction within and between basal ganglia nuclei is very often accompanied by synchronization at Parkinsonian rest tremor frequencies (3-10 Hz). These oscillations have a profound influence on thalamic projections and impair the thalamic relaying of cortical input by generating rebound action potentials. Our model describes convergent inhibitory input received from basal ganglia by the thalamocortical cells based on characteristics of normal activity, and/or low-frequency oscillations (activity associated with Parkinsons disease). In addition to simulated input, we also used microelectrode recordings as inputs for the model. In the resting state, and without additional sensorimotor input, pathological rebound activity is generated for even mild Parkinsonian input. We have found a specific stimulation window of amplitudes and frequencies for periodic input, which corresponds to high-frequency DBS, and which also suppresses rebound activity for mild and even more prominent Parkinsonian input. When low-frequency pathological rebound activity disables the thalamocortical cells ability to relay excitatory cortical input, a stimulation signal with parameter settings corresponding to our stimulation window can restore the thalamocortical cells relay functionality.

P300 deficits are present in young first-episode patients with schizophrenia and not in their healthy young siblings

OBJECTIVEnTo evaluated P300 (P3b) abnormalities in young first episode patients with schizophrenia and their healthy young siblings.nnnMETHODSnAn auditory oddball paradigm was used to assess P300 in 53 patients, 27 unaffected siblings and 28 healthy controls. Amplitude and latency of the three midline sites (Fz, Cz, and Pz) were compared between patients, siblings, and controls by a mixed-effects regression model.nnnRESULTSnP300 amplitude was significantly reduced in patients with schizophrenia but not in healthy siblings, when compared to healthy controls. P300 latency did not significantly differ between the three groups.nnnCONCLUSIONSnP300 amplitude but not latency was found to be affected in young patients with recent onset schizophrenia. However, P300 amplitude and latency were found not to be affected in healthy unaffected young siblings and, therefore, did not qualify as an endophenotype for schizophrenia.nnnSIGNIFICANCEnThe failure to find the P300 (P3b) abnormality in healthy siblings of patients with schizophrenia is an important finding and should be added to P300 literature.

Automatic subthalamic nucleus detection from microelectrode recordings based on noise level and neuronal activity.

Microelectrode recording (MER) along surgical trajectories is commonly applied for refinement of the target location during deep brain stimulation (DBS) surgery. In this study, we utilize automatically detected MER features in order to locate the subthalamic nucleus (STN) employing an unsupervised algorithm. The automated algorithm makes use of background noise level, compound firing rate and power spectral density along the trajectory and applies a threshold-based method to detect the dorsal and the ventral borders of the STN. Depending on the combination of measures used for detection of the borders, the algorithm allocates confidence levels for the annotation made (i.e. high, medium and low). The algorithm has been applied to 258 trajectories obtained from 84 STN DBS implantations. MERs used in this study have not been pre-selected or pre-processed and include all the viable measurements made. Out of 258 trajectories, 239 trajectories were annotated by the surgical team as containing the STN versus 238 trajectories by the automated algorithm. The agreement level between the automatic annotations and the surgical annotations is 88%. Taking the surgical annotations as the golden standard, across all trajectories, the algorithm made true positive annotations in 231 trajectories, true negative annotations in 12 trajectories, false positive annotations in 7 trajectories and false negative annotations in 8 trajectories. We conclude that our algorithm is accurate and reliable in automatically identifying the STN and locating the dorsal and ventral borders of the nucleus, and in a near future could be implemented for on-line intra-operative use.

Automatic noise-level detection for extra-cellular micro-electrode recordings

Extra-cellular neuro-recording signals used for functional mapping in deep brain stimulation (DBS) surgery and invasive brain computer interfaces, may suffer from poor signal to noise ratio. Therefore, a reliable automatic noise estimate is essential to extract spikes from recordings. We show that current methods are biased toward overestimation of noise-levels with increasing neuronal activity or artifacts. An improved and novel method is proposed that is based on an estimate of the mode of the distribution of the signal envelope. Our method makes use of the inherent characteristics of the noise distribution. For band-limited Gaussian noise the envelope of the signal is known to follow the Rayleigh distribution. The location of the peak of this distribution provides a reliable noise-level estimate. It is demonstrated that this new ‘envelope’ method gives superior performance both on simulated data, and on actual micro-electrode recordings made during the implantation surgery of DBS electrodes for the treatment of Parkinson’s disease.

Robust EMG-fMRI artifact reduction for motion (FARM)

OBJECTIVEnCurrent template-based artifact reduction methods are inadequate to reduce irregular volume- and slice-artifacts induced by limb motion in combined (surface) EMG-fMRI (electromyography-functional magnetic resonance imaging) studies. In addition, artifacts are not removed adequately for EMG frequencies above 50 Hz. We present a new fMRI artifact reduction algorithm for motion (FARM) and compare it with standard artifact correction as implemented in fMRI artifact slice-template removal (FASTR).nnnMETHODSnOne control subject generated motion artifacts during EMG-fMRI. Low-frequency motion artifacts and volume-artifacts were removed prior to slice-artifact correction. Slice-artifacts were phase-shifted and removed with motion adaptive templates (FARM). EMG data were also corrected applying FASTR.nnnRESULTSnTime traces demonstrate that artifacts related to sudden changes in wire position are contained to shorter time periods. EMG power spectra from neck and arm muscles show that FARM has improved performance at higher frequencies.nnnCONCLUSIONSnHigh-pass filtering, volume-artifact removal, phase-shifting and adaptation of slice-templates to motion improve the quality of artifact-corrected EMG recorded during limb motion.nnnSIGNIFICANCEnThe improved accuracy at which EMG-fMRI data can be obtained opens up new ways to directly relate self-paced movements to brain activations and to study patients suffering from movement disorders.

Antisaccade deficit is present in young first-episode patients with schizophrenia but not in their healthy young siblings

BACKGROUNDnResults of studies on antisaccade (AS) deficit in relatives of patients with schizophrenia are inconclusive. We hypothesized that AS performance in siblings of patients with schizophrenia is worse than in healthy controls and better than in patients with schizophrenia.nnnMETHODnWe included 55 first-episode patients with schizophrenia, 28 healthy siblings and 36 healthy controls to evaluate AS performance. Eye movements were measured electromagnetically by the double magnetic induction (DMI) method.nnnRESULTSnPatients with schizophrenia had a significantly higher error rate than siblings (d=0.86, p<0.0001) and controls (d=1.35, p<0.0001). Siblings had a higher mean error rate than healthy controls but this did not reach significance (d=0.56, p=0.29). The intra-class correlation (ICC) was 0.33 for the error rate. Mean AS gain was higher in siblings than in patients (d=0.75, p=0.004) and controls (d=0.6, p=0.05). The ICC was 0.08.nnnCONCLUSIONnAs parameters in strictly screened healthy young siblings of young first-episode patients with schizophrenia are comparable to results found in studies investigating older relatives. However, the statistical results (i.e. the ICCs) suggest that there is little evidence of shared environmental or genetic factors on error rate variation.

Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome : Report of three cases

OBJECTIVEnThree patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded.nnnMETHODSnEvent related potentials and event related spectral perturbations of EEG and LFP, event related cross-coherences between EEG/LFP and LFP/LFP were analyzed. As time locking events, the tic onsets were used. Spontaneous tics were compared to voluntary tic mimicking. The effect of tic suppression and DBS on thalamic LFPs was evaluated.nnnRESULTSnAll three patients showed time-locked and prior to onset of spontaneous motor tics thalamic synchronization and thalamo-cortical cross-coherence. Also in three patients, not time-locked to motor tics, increased intra-thalamic coherences in the 1-8Hz frequency band were found. In one patient it was demonstrated that voluntary mimicked tics were preceded by premotor cortical and thalamic potentials. In this patient unilateral thalamic DBS contralaterally decreased the background thalamic activity.nnnCONCLUSIONSnThe present study in three cases with TS shows that spontaneous tics in TS are preceded by repetitive coherent thalamo-cortical discharges, indicating that preceding a tic the basal ganglia circuits are charged up, ultimately leading to a motor tic.nnnSIGNIFICANCEnThalamic LFP recording may lead to more insight in underlying pathophysiological mechanisms in TS.

Advanced target identification in STN-DBS with beta power of combined local field potentials and spiking activity

BACKGROUNDnIn deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinsons Disease (PD), often microelectrode recordings (MER) are used for STN identification. However, for advanced target identification of the sensorimotor STN, it may be relevant to use local field potential (LFP) recordings. Then, it is important to assure that the measured oscillations are coming from the close proximity of the electrode.nnnNEW METHODnThrough multiple simultaneous recordings of LFP and neuronal spiking, we investigated the temporal relationship between local neuronal spiking and more global LFP. We analyzed the local oscillations in the LFP by calculating power only over specific frequencies that show a significant coherence between LFP and neuronal spiking. Using this coherence method, we investigated how well measurements in the sensorimotor STN could be discriminated from measurements elsewhere in the STN.nnnRESULTS/COMPARISON WITH EXISTING METHODSnThe sensorimotor power index (SMPI) of beta frequencies, representing the ability to discriminate sensorimotor STN measurements based on the beta power, was significantly larger using the coherence method for LFP spectral analysis compared to other methods where either the complete LFP beta spectrum or only the prominent peaks in the LFP beta spectrum were used to calculate beta power.nnnCONCLUSIONSnThe results suggest that due to volume conduction of beta frequency oscillations, proper localization of the sensorimotor STN with only LFP recordings is difficult. However, combining recordings of LFP and neuronal spiking and calculating beta power over the coherent parts of the LFP spectrum can be beneficial in discriminating the sensorimotor STN.