Intra-operative recordings of local field potentials can help localize the subthalamic nucleus in Parkinson's disease surgery

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be a highly effective treatment for Parkinson's disease (PD). However, therapeutic efficacy is limited by difficulties in consistently and correctly targeting this nucleus. Increasing evidence suggests that there is abnormal synchronization of beta frequency band activity (approximately 20 Hz) in the STN of PD patients, as reflected in the oscillatory nature of the local field potential (LFP). We hypothesized that an increase in the power of the LFP beta activity may provide intra-operative confirmation of STN targeting in patients undergoing STN implantation for the treatment of advanced PD. Accordingly, we recorded LFPs from the four contacts of DBS electrodes as the latter were advanced in 2 mm steps from a point 4-6 mm above the intended surgical target point in the STN, to a point 4 mm below this. Contacts were configured to give three bipolar recordings of LFPs. These were analyzed on 16 sides in 9 patients. The power in the 13-35 Hz band recorded at the lowest contact pair underwent a steep but focal increase during electrode descent. The depth of the peak beta activity showed excellent agreement with the level of the intra-operative clinical stun effect (k coefficient = 0.792). The depth of peak beta activity also showed 100% specificity and 100% sensitivity for placement within STN in comparison to pre- and Post-operative stereotactic MRI. Functional physiological localization of STN by the on-line spectral analysis of LFPs is quick to perform and may provide information directly relevant to the position of the electrode contact actually used for DBS.     

Subthalamic oscillatory activities at beta or higher frequency do not change after high-frequency DBS in Parkinson's disease

This study aimed to assess whether changes in the patterns of local field potential (LFP) oscillations of the subthalamic nucleus (STN) underlie to the clinical improvement within 60 s after turning off subthalamic DBS. We studied by spectral analysis the STN LFPs recorded in 13 nuclei from 7 patients with Parkinson's disease before and immediately after unilateral high-frequency (130 Hz) stimulation of the same nucleus, when the clinical benefit of DBS was unchanged. The results were compared with LFP data previously reported [A. Priori, G. Foffani, A. Pesenti, F. Tamma, A.M. Bianchi, M. Pellegrini et al., Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease. Exp. Neurol. 189 (2004) 369-379]--namely 13 STN from 9 parkinsonian patients recorded before and after levodopa administration--which were used as a control. Before DBS, in the 'off' clinical state after overnight withdrawal of dopaminergic therapy, the STN spectrum did not significantly differ from the control nuclei, showing prominent activity at beta frequencies (13-20 and 20-35 Hz). After DBS (10-15 min) of the STN, the recorded nuclei significantly differed from the control, failing to show significant changes either in the beta bands or at higher frequencies (60-90 and 250-350 Hz). The patterns of subthalamic LFP oscillations after DBS therefore differ from those after dopaminergic medication. These results suggest (1) that subthalamic LFP modulations are not the epiphenomenon of peripheral motor improvement and (2) that the transitory clinical efficacy maintained after discontinuation of subthalamic DBS is not associated with local modulation of LFP activity at beta or higher frequencies within the STN.     

The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease

Depth recordings in patients with Parkinson's disease (PD) have demonstrated prominent oscillatory activity in the beta frequency (13-35 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesized to contribute to bradykinesia, it is unclear to what extent the LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded both LFPs and multi-neuronal activity from microelectrodes inserted into STN in six PD patients (8 sides) during functional neurosurgery. As microelectrodes passed from above STN into STN, there was a pronounced increase in beta frequency band LFP activity. Furthermore, spike-triggered averages of LFP activity suggested that the discharges of neurons in STN were locked to beta oscillations in the LFP. The LFP is therefore likely to represent synchronous activity in populations of neurons in the STN of patients with PD.     

Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease

Power spectra from local field potentials (LFPs) recorded post-operatively from the deep brain stimulation (DBS) macroelectrode show prominence of the beta rhythm (11-30 Hz) in untreated Parkinson's disease (PD). Dopaminergic medication and movement attenuate this beta band in PD. In this pilot study of six sides in four patients, we recorded LFPs from the DBS electrode in untreated PD patients in the operating room. In all cases, there was a peak in the time-frequency spectrogram in the beta frequency range when the patients were at rest, which was associated with attenuation in the same range with movement. The actual frequency range and the strength of the beta peak varied among cases. In two patients, intra-operative constraints permitted recording of LFPs at rest, before and immediately after subthalamic nucleus (STN) DBS. In both patients we documented that STN DBS caused a significant attenuation in power in the beta band at rest that persisted for 15-25 s after DBS had been turned off (P < 0.01). From one case, our data suggest that the beta rhythm attenuation was most prominent within the STN itself. This study shows for the first time that STN DBS attenuates the power in the prominent beta band recorded in the STN of patients with PD. These pilot findings raise the interesting possibility of using this biomarker for closed loop DBS or neuromodulation.     

The STN beta-band profile in Parkinson's disease is stationary and shows prolonged attenuation after deep brain stimulation

Producing accurate movements may rely on the functional independence of sensorimotor circuits within basal ganglia nuclei. In parkinsonism there is abnormal synchrony of electrical activity within these circuits that results in a loss of independence across motor channels. Local field potential (LFP) recordings reflect the summation of local electrical fields and an increase in LFP power reflects increased synchrony in local neuronal networks. We recorded LFPs from the subthalamic nucleus (STN) deep brain stimulation (DBS) lead in the operating room in 22 cases from 16 subjects with Parkinson's disease (PD) who were off medication. There was elevated LFP power at beta frequencies (13-35 Hz) at rest. The LFP spectral profile was consistent across several periods of rest that were separated by movement and/or DBS, and appeared to be a relatively stationary phenomenon. The spectral profile and frequencies of the beta-band peak(s) varied among subjects but were similar between the right and left STNs within certain individuals. These results suggest that the LFP spectrum at rest may characterize a “signature” rhythm for an individual with PD. Beta-band power was attenuated after intra-operative STN DBS (p < 0.05). The attenuation lasted for 10 s after short periods (30 s) and for up to 50 s after longer periods (5 min) of DBS. The finding that longer periods of DBS attenuated beta power for a longer time suggests that there may be long-acting functional changes to networks in the STN in PD after chronic DBS.     

The effects of levodopa and ongoing deep brain stimulation on subthalamic beta oscillations in Parkinson's disease

Local field potentials (LFPs) recorded through electrodes implanted in the subthalamic nucleus (STN) for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) show that oscillations in the beta frequency range (8-20 Hz) decrease after levodopa intake. Whether and how DBS influences the beta oscillations and whether levodopa- and DBS-induced changes interact remains unclear. We examined the combined effect of levodopa and DBS on subthalamic beta LFP oscillations, recorded in nine patients with PD under four experimental conditions: without levodopa with DBS turned off; without levodopa with DBS turned on; with levodopa with DBS turned on; and with levodopa with DBS turned off. The analysis of STN-LFP oscillations showed that whereas levodopa abolished beta STN oscillations in all the patients (p = 0.026), DBS significantly decreased the beta oscillation only in five of the nine patients studied (p = 0.043). Another difference was that whereas levodopa completely suppressed beta oscillations, DBS merely decreased them. When we combined levodopa and DBS, the levodopa-induced beta disruption prevailed and combining levodopa and DBS induced no significant additive effect (p = 0.500). Our observations suggest that levodopa and DBS both modulate LFP beta oscillations.     

Time dependent subthalamic local field potential changes after DBS surgery in Parkinson's disease

Local field potentials (LFPs) recorded through electrodes implanted in patients with Parkinson's disease (PD) for deep brain stimulation (DBS) provided physiological information about the human basal ganglia. However, LFPs were always recorded 2–7 days after electrode implantation (“acute” condition). Because changes in the tissue surrounding the electrode occur after DBS surgery and could be relevant for LFPs, in this work we assessed whether impedance and LFP pattern are a function of the time interval between the electrode implant and the recordings. LFPs and impedances were recorded from 11 patients with PD immediately after (T-0h), 2 h after (T-2h), 2 days after (T-48h), and 1 month after (T-30d, “chronic” condition) surgery. Impedances at T-0h were significantly higher than at all the other time intervals (T-2h, p = 0.0005; T-48h, p = 0.0002; T-30d, p = 0.003). Correlated with this change (p = 0.005), the low-frequency band (2-7 Hz) decreased at all time intervals (p = 0.0005). Conversely, the low- (8–20 Hz) and the high-beta (21–35 Hz) bands increased in time (low-beta, p = 0.003; high beta, p = 0.022), but did not change between T-48h and T-30d. Our results suggest that DBS electrode impedance and LFP pattern are a function of the time interval between electrode implant and LFP recordings. Impedance decrease could be related to changes in the electrode/tissue interface and in the low-frequency band. Conversely, beta band modulations could raise from the adaptation of the neural circuit. These findings confirm that results from LFP analysis in the acute condition can be extended to the chronic condition and that LFPs can be used in novel closed-loop DBS systems.     

Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease

The subthalamic nucleus (STN) has a key role in the pathophysiology of Parkinson's disease and is the primary target for high-frequency deep brain stimulation (DBS). The STN rest electrical activity in Parkinson's disease, however, is still unclear. Here we tested the hypothesis that pharmacological modulation of STN activity has rhythm-specific effects in the classical range of EEG frequencies, below 50 Hz. We recorded local field potentials (LFPs) through electrodes implanted in the STN of patients with Parkinson's disease (20 nuclei from 13 patients). After overnight withdrawal of antiparkinsonian therapy, LFPs were recorded at rest both before (off) and after (on) acute administration of different antiparkinsonian drugs: levodopa, apomorphine, or orphenadrine. In the off-state, STN LFPs showed clearly defined peaks of oscillatory activity below 50 Hz: at low frequencies (2-7 Hz), in the alpha (7-13 Hz), low-beta (13-20 Hz), and high-beta range (20-30 Hz). In the on-state after levodopa and apomorphine administration, low-beta activity significantly decreased and low-frequency activity increased. In contrast, orphenadrine increased beta activity. Power changes elicited by levodopa and apomorphine at low frequencies and in the beta range were not correlated, whereas changes in the alpha band, which were globally not significant, correlated with the beta rhythm (namely, low beta: 13-20 Hz). In conclusion, in the human STN, there are at least two rhythms below 50 Hz that are separately modulated by antiparkinsonian medication: one at low frequencies and one in the beta range. Multiple rhythms are consistent with the hypothesis of multiple oscillating systems, each possibly correlating with specific aspects of human STN function and dysfunction.     

Subthalamic gamma activity in patients with Parkinson's disease

Depth recordings in patients with Parkinson's disease (PD) have demonstrated oscillatory activity in the gamma frequency (60-100 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesised to contribute to movement preparation, it is unclear to what extent these LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded LFPs and neuronal activity from microelectrodes inserted into the STN in PD patients during functional neurosurgery. Eight sides in seven patients out of 15 sides in 12 patients were identified that had peaks in the gamma band in spectra of LFPs. As microelectrodes descended towards STN, there was a pronounced increase in gamma frequency band LFP activity 1 mm above the line joining the anterior and posterior commissures and 2 mm above the microelectrode defined dorsal border of the STN. Gamma activity dropped again 3 mm below the microelectrode defined dorsal border of the STN. Spike-triggered averages of LFP activity suggested that the discharges of neurons in this region were locked to gamma oscillations in the LFP. Gamma band oscillations in the LFP are therefore likely to represent synchronous activity in populations of neurons in the upper STN and bordering zona incerta of patients with PD.     

Interhemispheric functional interactions between the subthalamic nuclei of patients with Parkinson's disease

Parkinson's disease (PD) is characterized by widespread neural interactions in cortico‐basal‐ganglia networks primarily in beta oscillations (approx. 10–30 Hz), as suggested by previous findings of levodopa‐modulated interhemispheric coherence between the bilateral subthalamic nuclei (STN) in local field potential recordings (LFPs). However, due to confounding effects of volume conduction the existence of ‘genuine’ interhemispheric subcortical coherence remains an open question. To address this issue we utilized the imaginary part of coherency (iCOH) which, in contrast to the standard coherence, is not susceptible to volume conduction. LFPs were recorded from eight patients with PD during wakeful rest before and after levodopa administration. We demonstrated genuine coherence between the bilateral STN in both 10–20 and 21–30 Hz oscillations, as revealed by a non‐zero iCOH. Crucially, increased iCOH in 10–20 Hz oscillations positively correlated with the worsening of motor symptoms in the OFF medication condition across patients, which was not the case for standard coherence. Furthermore, across patients iCOH was increased after levodopa administration in 21–30 Hz oscillations. These results suggest a functional distinction between low and high beta oscillations in STN‐LFP in line with previous studies. Furthermore, the observed functional coupling between the bilateral STN might contribute to the understanding of bilateral effects of unilateral deep brain stimulation. In conclusion, the present results imply a significant contribution of time‐delayed neural interactions to interhemispheric coherence, and the clinical relevance of long‐distance neural interactions between bilateral STN for motor symptoms in PD.     

Effects of Contralateral Deep Brain Stimulation and Levodopa on Subthalamic Nucleus Oscillatory Activity and Phase-Amplitude Coupling

BackgroundThe modulatory effects of medication and deep brain stimulation (DBS) on subthalamic nucleus (STN) neural activity in Parkinson's disease have been widely studied. However, effects on the contralateral side to the stimulated STN, in particular, changes in local field potential (LFP) oscillatory activity and phase-amplitude coupling (PAC), have not yet been reported.ObjectiveThe aim of this study was to examine changes in STN LFP activity across a range of frequency bands and STN PAC for different combinations of DBS and medication on/off on the side contralateral to the applied stimulation.Materials and MethodsWe examined STN LFPs that were recorded using externalized leads from eight parkinsonian patients during unilateral DBS from the side contralateral to the stimulation. LFP spectral power in alpha (5 to ～13 Hz), low beta (13 to ～20 Hz), high beta (20–30 Hz), and high gamma plus high-frequency oscillation (high gamma+HFO) (100–400 Hz) bands were estimated for different combinations of medication and unilateral stimulation (off/on). PAC between beta and high gamma+HFO in the STN LFPs was also investigated. The effect of the condition was examined using linear mixed models.ResultsPAC in the STN LFP was reduced by DBS when compared to the baseline condition (no medication and stimulation). Medication had no significant effect on PAC. Alpha power decreased with DBS, both alone and when combined with medication. Beta power decreased with DBS, medication, and DBS and medication combined. High gamma+HFO power increased during the application of contralateral DBS and was unaltered by medication.ConclusionsThe results provide new insights into the effects of DBS and levodopa on STN LFP PAC and oscillatory activity on the side contralateral to stimulation. These may have important implications in understanding mechanisms underlying motor improvements with DBS, including changes on both contralateral and ipsilateral sides, while suggesting a possible role for contralateral sensing during unilateral DBS.     

Thalamic single‐unit and local field potential activity in Tourette syndrome

Deep brain stimulation (DBS) of the ventralis oralis (VO) complex of the thalamus improves tics in patients with Tourette syndrome (TS). To neurophysiologically describe the VO complex we recorded, in seven patients with TS undergoing DBS electrode implantation, single‐unit activity during surgery and local field potentials (LFPs) a few days after surgery. Single unit recordings showed that the VO complex is characterized by a localized pattern of bursting neuronal activity. LFP spectra demonstrated that VO of TS patients has a prominent oscillatory activity at low frequencies (2–7 Hz) and in the α‐band (8–13 Hz), and a virtually absent beta activity. In each patient, the main LFP frequency significantly correlated with single‐unit interburst frequency. In conclusion, we observed an oscillatory bursting activity in the VO as target region in patients with severe TS undergoing DBS surgery. © 2010 Movement Disorder Society     

Altered Local Field Potential Relationship Between the Parafascicular Thalamic Nucleus and Dorsal Striatum in Hemiparkinsonian Rats

The thalamostriatal pathway is implicated in Parkinson's disease(PD); however, PD-related changes in the relationship between oscillatory activity in the centromedian-parafascicular complex(CM/Pf, or the Pf in rodents) and the dorsal striatum(DS) remain unclear.Therefore, we simultaneously recorded local field potentials(LFPs) in both the Pf and DS of hemiparkinsonian and control rats during epochs of rest or treadmill walking. The dopamine-lesioned rats showed increased LFP power in the beta band(12 Hz–35 Hz) in the Pf and DS during both epochs, but decreased LFP power in the delta(0.5 Hz–3 Hz) band in the Pf during rest epochs and in the DS during both epochs, compared to control rats. In addition,exaggerated low gamma(35 Hz–70 Hz) oscillations after dopamine loss were restricted to the Pf regardless of the behavioral state. Furthermore, enhanced synchronization of LFP oscillations was found between the Pf and DS after the dopamine lesion. Significant increases occurred in the mean coherence in both theta(3 Hz–7 Hz) and beta bands,and a significant increase was also noted in the phase coherence in the beta band between the Pf and DS during rest epochs. During the treadmill walking epochs, significant increases were found in both the alpha(7 Hz–12 Hz)and beta bands for two coherence measures. Collectively,dramatic changes in the relative LFP power and coherence in the thalamostriatal pathway may underlie the dysfunction of the basal ganglia-thalamocortical network circuits in PD, contributing to some of the motor and non-motor symptoms of the disease.     

Conflict-dependent dynamic of subthalamic nucleus oscillations during moral decisions

Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the neural mechanisms of judgement and decision-making, all these works focused on the cerebral cortex, without investigating the role of subcortical structures such as the basal ganglia. Besides being an effective therapeutic tool, deep brain stimulation (DBS) allows local field potential (LFP) recordings through the stimulation electrodes thus providing a physiological “window” on human subcortical structures. In this study we assessed whether subthalamic nucleus LFP oscillations are modulated by processing of moral conflictual, moral nonconflictual, and neutral statements. To do so, in 16 patients with Parkinson's disease (8 men) bilaterally implanted with subthalamic nucleus (STN) electrodes for DBS, we recorded STN LFPs 4 days after surgery during a moral decision task. During the task, recordings from the STN showed changes in LFP oscillations. Whereas the 14–30 Hz band (beta) changed during the movement executed to perform the task, the 5–13 Hz band (low-frequency) changed when subjects evaluated the content of statements. Low-frequency band power increased significantly more during conflictual than during nonconflictual or neutral sentences. We conclude that STN responds specifically to conflictual moral stimuli, and could be involved in conflictual decisions of all kinds, not only those for moral judgment. LFP oscillations provide novel direct evidence that the neural processing of conflictual decision-making spreads beyond the cortex to the basal ganglia and encompasses a specific subcortical conflict-dependent component.     

Conflict-dependent dynamic of subthalamic nucleus oscillations during moral decisions

Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the neural mechanisms of judgement and decision-making, all these works focused on the cerebral cortex, without investigating the role of subcortical structures such as the basal ganglia. Besides being an effective therapeutic tool, deep brain stimulation (DBS) allows local field potential (LFP) recordings through the stimulation electrodes thus providing a physiological "window" on human subcortical structures. In this study we assessed whether subthalamic nucleus LFP oscillations are modulated by processing of moral conflictual, moral nonconflictual, and neutral statements. To do so, in 16 patients with Parkinson's disease (8 men) bilaterally implanted with subthalamic nucleus (STN) electrodes for DBS, we recorded STN LFPs 4 days after surgery during a moral decision task. During the task, recordings from the STN showed changes in LFP oscillations. Whereas the 14--30 Hz band (beta) changed during the movement executed to perform the task, the 5--13 Hz band (low-frequency) changed when subjects evaluated the content of statements. Low-frequency band power increased significantly more during conflictual than during nonconflictual or neutral sentences. We conclude that STN responds specifically to conflictual moral stimuli, and could be involved in conflictual decisions of all kinds, not only those for moral judgment. LFP oscillations provide novel direct evidence that the neural processing of conflictual decision-making spreads beyond the cortex to the basal ganglia and encompasses a specific subcortical conflict-dependent component.     

Combining Multimodal Biomarkers to Guide Deep Brain Stimulation Programming in Parkinson Disease

BackgroundDeep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease.ObjectiveIn this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold).Materials and MethodsSTN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature.ResultsBoth resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction.ConclusionLFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.     

Differential distribution of coherence between beta-band subthalamic oscillations and forearm muscles in Parkinson’s disease during isometric contraction

ObjectiveUnder rest condition, beta-band (13–30 Hz) activity in patients with Parkinson’s disease (PD) is prominent in the subthalamic nucleus (STN). However, the beta-band coupling between STN and muscle activity, its distribution and relation to motor symptoms remains unclear.MethodsUsing up to five electrodes, we recorded local field potentials (LFPs) above (zona incerta, ZI) and within the STN at different recording heights in 20 PD patients during isometric contraction. Simultaneously, we registered activity of the contralateral flexor and extensor muscle. We analysed LFP–EMG coherence to estimate coupling in the frequency domain.ResultsCoherence analysis showed beta–associated coupling in the ZI and STN with more significant LFP–EMG coherences in the STN. Coherence varied depending on the localisation of the LFP and muscles. We found significant difference between coherence of the extensor and the flexor muscle to the same LFP (p = 0.045).ConclusionsWe demonstrated that coherence between beta-band oscillations and forearm muscles are differentially distributed in the subthalamic region and between the forearm muscles in Parkinson’s disease during isometric contraction. However, the significant LFP–EMG coupling did not associate with motor deficits in PD patients.SignificanceThe differential distribution of beta-band activity in the STN highlights the importance of a topographically distinct therapeutic modulation.     

Gender-related differences in the human subthalamic area: a local field potential study

The objective of this study was to investigate the possible existence of gender-related neurophysiological differences in the oscillatory activity of the human subthalamic area. To this end, we recorded local field potentials (LFPs) after neurosurgical procedures for deep brain stimulation (DBS) in 24 patients (12 males and 12 females) with Parkinson's disease. LFP recordings at rest before levodopa medication (19 nuclei from 11 female patients and 16 nuclei from ten male patients) showed significantly higher power in the alpha/low-beta band (8-12 Hz, P<0.01; 13-20 Hz, P=0.03) in females than in males. After levodopa medication (ten nuclei from six female patients and 11 nuclei from seven male patients), the power in the high-gamma band (60-90 Hz) and of the 300 Hz rhythm was significantly higher in females than in males (high-gamma, P=0.007; 300 Hz, P=0.002). These findings show that functional gender-related differences in the central nervous system involve the human subthalamic area (STN) and its response to levodopa in Parkinson's disease. Gender-related neurophysiological differences may be important for understanding gender-specific features of neurodegenerative disorders and should be considered when interpreting LFP data from the human basal ganglia.     

Low-frequency subthalamic oscillations increase after deep brain stimulation in Parkinson's disease

This work is the second of a series of papers in which we investigated the neurophysiological basis of deep brain stimulation (DBS) clinical efficacy using post-operative local field potential (LFP) recordings from DBS electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease. We found that low-frequency (1-1.5Hz) oscillations in LFP recordings from the STN of patients with Parkinson's disease dramatically increase after DBS of the STN itself (log power change=0.93+/-0.62; Wilcoxon: p=0.0002, n=13), slowly decaying to baseline levels after turning DBS off. The DBS-induced increase of low-frequency LFP oscillations is highly reproducible and appears only after the delivery of DBS for a time long enough to induce clinical improvement. This increase of low-frequency LFP oscillations could reflect stimulation-induced modulation of network activity or could represent changes of the electrochemical properties at the brain-electrode interface.     

An electronic device for artefact suppression in human local field potential recordings during deep brain stimulation

The clinical efficacy of high-frequency deep brain stimulation (DBS) for Parkinson's disease and other neuropsychiatric disorders likely depends on the modulation of neuronal rhythms in the target nuclei. This modulation could be effectively measured with local field potential (LFP) recordings during DBS. However, a technical drawback that prevents LFPs from being recorded from the DBS target nuclei during stimulation is the stimulus artefact. To solve this problem, we designed and developed 'FilterDBS', an electronic amplification system for artefact-free LFP recordings (in the frequency range 2-40 Hz) during DBS. After defining the estimated system requirements for LFP amplification and DBS artefact suppression, we tested the FilterDBS system by conducting experiments in vitro and in vivo in patients with advanced Parkinson's disease undergoing DBS of the subthalamic nucleus (STN). Under both experimental conditions, in vitro and in vivo, the FilterDBS system completely suppressed the DBS artefact without inducing significant spectral distortion. The FilterDBS device pioneers the development of an adaptive DBS system retroacted by LFPs and can be used in novel closed-loop brain-machine interface applications in patients with neurological disorders.