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The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random 'start' and 'stop' cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional 'start' and 'stop' cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity. Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) can be divided into postural instability and difficult gait (PIGD) and tremor dominance (TD) subtypes. However, potential neural markers located in the dorsal ventral side of the subthalamic nucleus (STN) for delineating the two subtypes of PIGD and TD have not been demonstrated. Therefore, this study aimed to investigate the spectral characteristics of PD on the dorsal ventral side. The differences in the β oscillation spectrum of the spike signal on the dorsal and ventral sides of the STN during deep brain stimulation (DBS) were investigated in 23 patients with PD, and coherence analysis was performed for both subtypes. Finally, each feature was associated with the Unified Parkinson's Disease Rating Scale (UPDRS). The β power spectral density (PSD) in the dorsal STN was found to be the best predictor of the PD subtype, with 82.6% accuracy. The PSD of dorsal STN β oscillations was greater in the PIGD group than in the TD group (22.17% vs. 18.22%; p < 0.001). Compared with the PIGD group, the TD group showed greater consistency in the β and γ bands. In conclusion, dorsal STN β oscillations could be used as a biomarker to classify PIGD and TD subtypes, guide STN-DBS treatment, and relate to some motor symptoms. [ABSTRACT FROM AUTHOR]

• It described the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. • The burst neurons account for highest (90 %) in NAc. • Among different nuclei, the mean firing rate (MFR) was the highest (1.94 Hz) in NAc. • MFR increased after entering the NAc and decreased after entering the ALIC. • The single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory. The nucleus accumbens (NAc) and the anterior limb of internal capsule (ALIC) are effective targets for treating addiction using deep brain stimulation (DBS). However, there have been no reports on the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. This study aimed to investigate the electrical activity characteristics of neurons in the NAc and ALIC using microelectrode recording (MER) during DBS surgery in patients with addiction, and six patients with addiction were included (five with heroin addiction and one with alcohol addiction). The microelectrode recording trajectories were reconstructed and recording sites at different depths were determined by merging the pre- and post-operative images in the FrameLink system. The results showed that among the 256 neurons, 204 (80 %) were burst neurons. NAc neurons accounted for the majority (57 %), and the mean firing rate (MFR) was the highest (1.94 Hz). ALIC neurons accounted for the least (14 %), and MFR was the lowest (0.44 Hz). MFR increased after entering the NAc and decreased after entering the ALIC. In the patients with addiction treated using DBS, the single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) can be divided into postural instability and difficult gait (PIGD) and tremor dominance (TD) subtypes. However, potential neural markers located in the dorsal ventral side of the subthalamic nucleus (STN) for delineating the two subtypes of PIGD and TD have not been demonstrated. Therefore, this study aimed to investigate the spectral characteristics of PD on the dorsal ventral side. The differences in the β oscillation spectrum of the spike signal on the dorsal and ventral sides of the STN during deep brain stimulation (DBS) were investigated in 23 patients with PD, and coherence analysis was performed for both subtypes. Finally, each feature was associated with the Unified Parkinson’s Disease Rating Scale (UPDRS). The β power spectral density (PSD) in the dorsal STN was found to be the best predictor of the PD subtype, with 82.6% accuracy. The PSD of dorsal STN β oscillations was greater in the PIGD group than in the TD group (22.17% vs. 18.22%; p < 0.001). Compared with the PIGD group, the TD group showed greater consistency in the β and γ bands. In conclusion, dorsal STN β oscillations could be used as a biomarker to classify PIGD and TD subtypes, guide STN-DBS treatment, and relate to some motor symptoms.

Parkinson’s disease (PD) is treated effectively by deep brain stimulation (DBS) of the subthalamic nucleus (STN), using an electrode inserted into the head of a PD patient. The electrode has multiple electrical contacts along its length, so the best may be chosen for selectively stimulating the STN. Neurosurgeons usually determine the optimal stimulated contact via the clinical experience of the neurosurgeon and the motor improvement of PD patients. This is a time-consuming and labor-intensive trial-and-error process. The selection of optimal stimulated contact highly depends on the locations of sweet spots, which are manually identified by the characteristic features of microelectrode recordings (MERs). This paper presents an amplitude-frequency-aware deep fusion network for optimal contact selection on STN-DBS electrodes. The method first obtains the amplitude-frequency fusion features by combining the MERs time sequence features and the amplitude sequence features, and then uses the convolutional neural network (CNN) with convolutional block attention module (CBAM) to identify both the border of the STN and the sweet spots to implant the electrode. The optimal stimulated contact can be selected according to the distribution of the sweet spots. Experimental results indicate that, for successful surgeries, neurosurgeons and the proposed AI solution selected the same optimal contacts. Furthermore, the proposed method outperforms the state-of-the-art methods for STN and sweet spot identification. The proposed method shows great potential for optimal contact selection to improve the efficiency of STN-DBS surgery and reduce the dependence on clinicians’ experience. [ABSTRACT FROM AUTHOR]

Precise stereotactic targeting of the dorsolateral motor part of the subthalamic nucleus (STN) is paramount for maximizing clinical effectiveness and preventing side effects of deep brain stimulation (DBS) in patients with advanced Parkinson's disease. With recent developments in magnetic resonance imaging (MRI) techniques, direct targeting of the dorsolateral part of the STN is now feasible, together with visualization of the motor fibers in the nearby internal capsule. However, clinically relevant discrepancies were reported when comparing STN borders on MRI to electrophysiological STN borders during microelectrode recordings (MER). Also, one should take into account the possibility of a 3D inaccuracy of up to 2 mm of the applied stereotactic technique. Pneumocephalus and image fusion errors may further increase implantation inaccuracy. Even when implantation has been successful, suboptimal lead anchoring on the skull may cause lead migration during follow-up. Meticulous pre- and intraoperative imaging is therefore indispensable, and so is postoperative imaging when the effects of DBS deteriorate during follow-up. Thus far, most DBS centers employ MRI targeting, multichannel MER, and awake test stimulation in STN surgery, but randomized trials comparing surgery under local versus general anesthesia and additional studies comparing MER-STN borders to high-field MRI-STN may change this clinical practice. Further developments in imaging protocols and improvements in image fusion processes are needed to optimize placement of DBS leads in the dorsolateral motor part of the STN in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Objective: Asleep deep brain stimulation (DBS) for Parkinson's disease (PD) is being performed more frequently; however, motor outcomes and safety of asleep DBS have never been assessed in a prospective randomized trial. Methods: We conducted a prospective, randomized, noncomparative trial to assess the motor outcomes of asleep DBS. Leads were implanted in the subthalamic nucleus (STN) according to probabilistic stereotactic coordinates with a surgical robot under O-arm© imaging guidance under either general anesthesia without microelectrode recordings (MER) (20 patients, asleep group) or local anesthesia with MER and clinical testing (9 patients, awake group). Results: The mean motor improvement rates on the Unified Parkinson's Disease Rating Scale Part III (UPDRS-3) between OFF and ON stimulation without medication were 52.3% (95% CI: 45.4–59.2%) in the asleep group and 47.0% (95% CI: 23.8–70.2%) in the awake group, 6 months after surgery. Except for a subcutaneous hematoma, we did not observe any complications related to the surgery. Three patients (33%) in the awake group and 8 in the asleep group (40%) had at least one side effect potentially linked with neurostimulation. Conclusions: Owing to its randomized design, our study supports the hypothesis that motor outcomes after asleep STN-DBS in PD may be noninferior to the standard awake procedure. [ABSTRACT FROM AUTHOR]

Background: We obtained microelectrode recordings from four patients with intractable aggressivity who underwent surgery at posteromedial hypothalamus under general anaesthesia. We described two general types of extracellular action potentials (EAPs): typical/canonical and atypical. Methods: We analysed 337 units and 67 traces, which were characterized by the mean action potential (mAP). For the first phase, depolarization and repolarization, we computed amplitudes (VFP, VDep and VRep) and durations (dFP, dDep and dRep), maximum and minimum values of the first derivative (dVmax, dVmin), and amplitude and duration ratios. Results: Most of the canonical mAPs were positive (81.1%). EAPs with atypical mean action potentials (amAPs) were recorded in 42/337 cases. Only 35.6% of mAPs showed 2 phases. We identified the following types: N1P1N2 (38.3%), P1N1 (35.9%), amAP (12.5%), P1P2N1 (12.2%), N1P1 (4.7%), P1N1P2 (4.1%) and N1N2P1 (3.2%). We can define the properties of canonical forms as those units with (i) at least two opposite phases; (ii) VDep∈[1.2,2.7]×|VRep| and strongly related by this function VRep=-0.56⁢(±0.01)⁢VDep-1.83⁢(±0.79); (iii) a very strong relationship between dVmax and dVmin, given by the equation d⁢Vmin=-0.91⁢(±0.03)⁢d⁢Vmax-0.37⁢(±0.12), both of which were included in the depolarization phase; (iv) related with VDep by the equation d⁢Vmax=0.08⁢(±0.001)⁢VDep-0.28⁢(±0.14); and (v) dDep⁢~⁢0.38⁢dRep. However, the first phase does not pertain to the same dynamic process responsible for depolarization and repolarization. Conclusions: Atypical units are described here for the first time and are true EAPs that differ strikingly from canonical forms. To date, they have been observed only in the hypothalamus, but future research is needed to assess their existence in other brain structures.

Between seizures the brain of patients with epilepsy generates pathological patterns of synchronous activity, designated as interictal epileptiform discharges (ID). Using microelectrodes in the hippocampal formations of 8 patients with drug-resistant temporal lobe epilepsy, we studied ID by simultaneously analyzing action potentials from individual neurons and the local field potentials (LFPs) generated by the surrounding neuronal network. We found that ~30% of the units increased their firing rate during ID and 40% showed a decrease during the post-ID period. Surprisingly, 30% of units showed either an increase or decrease in firing rates several hundred of milliseconds before the ID. In 4 patients, this pre-ID neuronal firing was correlated with field high-frequency oscillations at 40-120 Hz. Finally, we observed that only a very small subset of cells showed significant coincident firing before or during ID. Taken together, we suggested that, in contrast to traditional views, ID are generated by a sparse neuronal network and followed a heterogeneous synchronization process initiated over several hundreds of milliseconds before the paroxysmal discharges.

Objective: Deep brain stimulation (DBS) is an effective treatment for medically refractory movement disorders and other neurological conditions. To comprehensively characterize the prevalence, locations, timing of detection, clinical effects, and risk factors of DBS-related intracranial hemorrhage (ICH), the authors performed a systematic review of the published literature., Methods: PubMed, EMBASE, and Web of Science were searched using 2 concepts: cerebral hemorrhage and brain stimulation, with filters for English, human studies, and publication dates 1980-2023. The inclusion criteria were the use of DBS intervention for any human neurological condition, with documentation of hemorrhagic complications by location and clinical effect. Studies with non-DBS interventions, no documentation of hemorrhage outcome, patient cohorts of ≤ 10, and pediatric patients were excluded. The risk of bias was assessed using Centre for Evidence-Based Medicine Levels of Evidence. The authors performed proportional meta-analysis for ICH prevalence., Results: A total of 63 studies, with 13,056 patients, met the inclusion criteria. The prevalence of ICH was 2.9% (fixed-effects model, 95% CI 2.62%-3.2%) per patient and 1.6% (random-effects model, 95% CI 1.34%-1.87%) per DBS lead, with 49.6% being symptomatic. The ICH rates did not change with time. ICH most commonly occurred around the DBS lead, with 16% at the entry point, 31% along the track, and 7% at the target. Microelectrode recording (MER) during DBS was associated with increased ICH rate compared to DBS without MER (3.5 ± 2.2 vs 2.1 ± 1.4; p[T ≤ t] 1-tail = 0.038). Other reported ICH risk factors include intraoperative systolic blood pressure > 140 mm Hg, sulcal DBS trajectories, and multiple microelectrode insertions. Sixty percent of ICH was detected at 24 hours postoperatively and 27% intraoperatively. The all-cause mortality rate of DBS was 0.4%, with ICH accounting for 22% of deaths. Single-surgeon DBS experience showed a weak inverse correlation (r = -0.27, p = 0.2189) between the rate of ICH per lead and the number of leads implanted per year., Conclusions: This study provides level III evidence that MER during DBS is a risk factor for ICH. Other risk factors include intraoperative systolic blood pressure > 140 mm Hg, sulcal trajectories, and multiple microelectrode insertions. Avoidance of these risk factors may decrease the rate of ICH.

Introduction: For deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) in Parkinson's disease (PD), many centers employ visualization of the nucleus on magnetic resonance imaging (MRI), intraoperative microelectrode recordings (MER), and test stimulation in awake patients. The value of these steps is a subject for ongoing debate. In the current study, we determined the relative contribution of MRI targeting, multitrack MER, and awake test stimulation in final lead placement during STN DBS surgery for PD. Methods: Data on PD patients undergoing MRI-targeted STN DBS surgery with three-channel MER and awake test stimulation between February 2010 and January 2014 were analyzed to determine in which MER trajectory final leads were implanted and why this tract was chosen. Results: Seventy-six patients underwent implantation of 146 DBS leads. In 92% of the STN, the final leads were implanted in one of the three planned channels. In 6%, additional channels were needed. In 2%, surgery was aborted before final lead implantation due to anxiety or fatigue. The final leads were implanted in the channels with the longest STN MER signal trajectory in 60% of the STN (38% of the bilaterally implanted patients). This was the central channel containing the MRI target in 39% of the STN (18% bilaterally). The most frequently noted reasons why another channel than the central channel was chosen for final lead placement were (1) a lower threshold for side effects (54%) and (2) no or a too short trajectory of the STN MER signal (40%) in the central channel. The latter reason correlated with larger 2D (x and y) errors in our stereotactic method. Conclusions: STN DBS leads were often not implanted in the MRI-planned trajectory or in the trajectory with the longest STN MER signal. Thresholds for side effects during awake test stimulation were decisive for final target selection in the majority of patients. [ABSTRACT FROM AUTHOR]

• Very high frequency oscillations in the thalamus are not produced in the ventral caudate nucleus only. • High frequency oscillations in the ventral caudate nucleus reflect the synapses of thalamic neurons. • High frequency oscillations can be a specific landmark for sensory thalamus in anaesthetized patients. During deep brain stimulation (DBS) surgery, we analysed somatosensory evoked potentials (SSEPs) using microelectrode recordings (MERs) in patients under general anaesthesia. We obtained MERs from 5 patients with refractory epilepsy. Off-line analysis isolated local field potentials (LFPs, 2–200 Hz) and high frequency components (HFCs, 0.5–5 kHz). Trajectories were reconstructed off-line. The ventral caudate (V.c.) nucleus was most frequently recorded from (171 mm). Very high frequency oscillations (VHFOs) were recorded up to 8 mm in length from all 4 electrodes but were most frequently recorded from the V.c. The properties of VHFOs were similar among all nuclei (frequency >1500 Hz, amplitude ∼3 µV, starting time ∼14 ms, duration 8–9 ms). Consecutive recordings did not show any synchronization or propagation, but a new kind of potential (high frequency oscillation, HFO) appeared abruptly inside the V.c. (frequency = 848 ± 66 Hz, amplitude = 5.2 ± 1.8 µV starting at 17.7 ± 0.5 ms, spanning 3.4 ± 0.3 ms). VHFOs are widely extending and cannot be ascribed to the V.c. HFOs in patients under general anaesthesia can serve as a landmark to identify the V.c. in thalamic DBS surgery. Thalamic processing involves nuclei other than the V.c, and HFO can be used to improve DBS surgery. [ABSTRACT FROM AUTHOR]

The pedunculopontine nucleus (PPN) is engaged in posture and gait control, and neuronal degeneration in the PPN has been associated with Parkinsonian disorders. Clinical outcomes of deep brain stimulation of the PPN in idiopathic Parkinson's disease (IPD) and progressive supranuclear palsy (PSP) differ, and we investigated whether the PPN is differentially affected in these conditions. We had the rare opportunity to record continuous electrophysiological data intraoperatively in 30 s blocks from single microelectrode contacts implanted in the PPN in six PSP patients and three IPD patients during rest, passive movement, and active movement. Neuronal spikes were sorted according to shape using a wavelet-based clustering approach to enable comparisons between individual neuronal firing rates in the two disease states. The action potential widths showed a bimodal distribution consistent with previous findings, suggesting spikes from noncholinergic (likely glutamatergic) and cholinergic neurons. A higher PPN spiking rate of narrow action potentials was observed in the PSP than in the IPD patients when pooled across all three conditions (Wilcoxon rank sum test: p = 0.0141). No correlation was found between firing rate and disease severity or duration. The firing rates were higher during passive movement than rest and active movement in both groups, but the differences between conditions were not significant. PSP and IPD are believed to represent distinct disease processes, and our findings that the neuronal firing rates differ according to disease state support the proposal that pathological processes directly involving the PPN may be more pronounced in PSP than IPD. [ABSTRACT FROM AUTHOR]

• Propofol increased bursting and decreased firing rate in STN single units. • Propofol influenced the interplay of parameters of neuronal activity in STN. • Random forest algorithm fits better to predict the state of neuronal activity. The analysis of neuronal activity in human brain is a complicated task as it meets several limitations, including small sample sizes, dependent variables in the dataset and the short duration of recordings that entangles the analysis procedure. Here, we present the comparative research of neuronal activity in subthalamic nucleus (STN) of 8 Parkinsonian patients undergoing DBS surgery in awake state and under propofol anaesthesia using different statistical approaches. We studied 25 parameters of single unit activity and performed a direct comparison of the parameters between the groups to characterise the changes in STN activity under anaesthesia. We found a significant decrease in firing rate and a prominent increase in bursting of neurons in the anaesthetised state. Also, these data were used to determine the most important parameters for classification. We revealed the differences between parametric and nonparametric approaches regarding the identification of the most important spike train features. The random forest trees algorithm showed a greater accuracy of classification (91.7 ± 1.8%) compared to generalised linear models (82.4 ± 3.8%). The lists of the features important for classification according to F-scores and random forest trees also differed markedly. Our results indicate that feature interactions play a key role in neuronal activity analysis and must be taken into account. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) is an accepted treatment for patients with medication-resistant Tourette syndrome (TS). Sedation is commonly required during electrode implantation to attenuate anxiety, pain, and severe tics. Anesthetic agents potentially impair the quality of microelectrode recordings (MER). Little is known about the effect of these anesthetics on MER in patients with TS. We describe our experience with different sedative regimens on MER and tic severity in patients with TS. Methods: The clinical records of all TS patients who underwent DBS surgery between 2010 and 2018 were reviewed. Demographic data, stimulation targets, anesthetic agents, perioperative complications, and MER from each hemisphere were collected and analyzed. Single-unit activity was identified by filtering spiking activity from broadband MER data and principal component analysis with K-means clustering. Vocal and motor tics which caused artifacts in the MER data were manually selected using visual and auditory inspection. Results: Six patients underwent bilateral DBS electrode implantation. In all patients, the target was the anterior internal globus pallidus. Patient comfort and hemodynamic and respiratory stability were maintained with conscious sedation with one or more of the following anesthetic drugs: propofol, midazolam, remifentanil, clonidine, and dexmedetomidine. Good quality MER and clinical testing were obtained in 9 hemispheres of 6 patients. In 3 patients, MER quality was poor on one side. Conclusion: Cautiously applied sedative drugs can provide patient comfort, hemodynamic and respiratory stability, and suppress severe tics, with minimal interference with MER. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising treatment for patients with refractory epilepsy. However, therapy response varies and precise positioning of the DBS lead is potentially essential for maximizing therapeutic efficacy. We investigate if single-cell recordings acquired by microelectrode recordings can aid targeting of the ANT during surgery and hypothesize that the neuronal firing properties of the target region relate to clinical outcome. We prospectively included 10 refractory epilepsy patients and performed microelectrode recordings under general anesthesia to identify the change in neuronal signals when approaching and transecting the ANT. The neuronal firing properties of the target region, anatomical locations of microelectrode recordings and active contact positions of the DBS lead along the recorded trajectory were compared between responders and nonresponders to DBS. We obtained 19 sets of recordings from 10 patients (five responders and five nonresponders). Amongst the 403 neurons detected, 365 (90.6%) were classified as bursty. Entry into the ANT was characterized by an increase in firing rate while exit of the ANT was characterized by a decrease in firing rate. Comparing the trajectories of responders to nonresponders, we found differences neither in the neuronal firing properties themselves nor in their locations relative to the position of the active contact. Single-cell firing rate acquired by microelectrode recordings under general anesthesia can thus aid targeting of the ANT during surgery, but is not related to clinical outcome in DBS for patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]

Background: 7.0-T T2-weighted MRI offers excellent visibility of the subthalamic nucleus (STN), which is used as a target for deep brain stimulation (DBS) in Parkinson's disease (PD). A comparison of 7.0-T MRI to microelectrode recordings (MER) for STN border identification has not been performed. Objective: To compare representation of STN borders on 7.0-T T2 MRI with the borders identified during MER in patients undergoing DBS for PD and to evaluate whether STN identification on 7.0-T T2 MRI leads to alterations in stereotactic target planning. Design/Methods: STN border identification was done using volumetric 7.0-T T2 MRI acquisitions. This was compared to the STN borders identified by MER. STN target planning was independently performed by 3 DBS surgeons on T2 imaging using 1.5-, 3.0-, and 7.0-T MRI. Results: A total of 102 microelectrode tracks were evaluated in 19 patients. Identification of the dorsal STN border was well feasible on 7-T T2, whereas the ventral STN was un-distinguishable from the substantia nigra. The dorsal STN border on MRI was located more dorsal than MER in 73% of trajectories. The average distance from MRI to MER border was 0.9 mm (range –4.4 to +3.5 mm). STN target planning showed high correspondence between the 3 field strengths. Conclusion: 7.0-T T2 MRI offers the possibility of easy identification of the dorsal border of the STN. However, higher field strength MRI does not change the planning of the target. Compared to MER, the dorsal border on MRI was located more dorsal in the majority of cases, situating MER activity within STN representation. [ABSTRACT FROM AUTHOR]

Our objective was to describe the electrophysiological properties of the extracellular action potential (AP) picked up through microelectrode recordings (MERs). Five patients were operated under general anesthesia for centromedian deep brain stimulation (DBS). APs from the same cell were pooled to obtain a mean AP (mAP). The amplitudes and durations for all 2/3 phases were computed from the mAP, together with the maximum (dVmax) and minimum (dVmin) values of the first derivative, as well as the slopes of different phases during repolarization. The mAPs are denominated according to the phase polarity (P/N for positive/negative). We obtained a total of 1109 mAPs, most of the positive (98.47%) and triphasic (93.69%) with a small P/N deflection (Vphase1) before depolarization. The percentage of the different types of mAPs was different for the nuclei addressed. The relationship between dVmax and the depolarizing phase is specific. The descending phase of the first derivative identified different phases during the repolarizing period. We observed a high correlation between Vphase1 and the amplitudes of either depolarization or repolarization phases. Human thalamic nuclei differ in their electrophysiological properties of APs, even under general anesthesia. Capacitive current, which is probably responsible for Vphase1, is very common in thalamic APs. Moreover, subtle differences during repolarization are neuron-specific.

Although motor subtypes of Parkinson's disease (PD), such as tremor dominant (TD) and postural instability and gait difficulty (PIGD), have been defined based on symptoms since the mid- 1990s, no underlying neural correlates of these clinical subtypes have yet been identified. Very limited data exist regarding the electrophysiological abnormalities within the subthalamic nucleus (STN) that likely accompany the symptom severity or the phenotype of PD. Here, we show that activity in subbands of local field potentials (LFPs) recorded with multiple microelectrodes from subterritories of STN provide distinguishing neurophysiological information about the motor subtypes of PD. We studied 24 patients with PD and found distinct patterns between TD (n = 13) and PIGD (n = 11) groups in high-frequency oscillations (HFOs) and their nonlinear interactions with beta band in the superior and inferior regions of the STN. Particularly, in the superior region of STN, the power of the slow HFO (sHFO) (200-260 Hz) and the coupling of its amplitude with beta-band phase were significantly stronger in the TD group. The inferior region of STN exhibited fast HFOs (fHFOs) (260-450 Hz), which have a significantly higher center frequency in the PIGD group. The cross-frequency coupling between fHFOs and beta band in the inferior region of STN was significantly stronger in the PIGD group. Our results indicate that the spatiospectral dynamics of STN-LFPs can be used as an objective method to distinguish these two motor subtypes of PD. These observations might lead to the development of sensing and stimulation strategies targeting the subterritories of STN for the personalization of deep-brain stimulation (DBS). [ABSTRACT FROM AUTHOR]

Background Extracellular microelectrode recording (MER) is a prominent technique for studies of extracellular single-unit neuronal activity. In order to achieve robust results in more complex analysis pipelines, it is necessary to have high quality input data with a low amount of artifacts. We show that noise (mainly electromagnetic interference and motion artifacts) may affect more than 25% of the recording length in a clinical MER database. New method We present several methods for automatic detection of noise in MER signals, based on (i) unsupervised detection of stationary segments, (ii) large peaks in the power spectral density, and (iii) a classifier based on multiple time- and frequency-domain features. We evaluate the proposed methods on a manually annotated database of 5735 ten-second MER signals from 58 Parkinson's disease patients. Comparison with existing methods The existing methods for artifact detection in single-channel MER that have been rigorously tested, are based on unsupervised change-point detection. We show on an extensive real MER database that the presented techniques are better suited for the task of artifact identification and achieve much better results. Results The best-performing classifiers (bagging and decision tree) achieved artifact classification accuracy of up to 89% on an unseen test set and outperformed the unsupervised techniques by 5–10%. This was close to the level of agreement among raters using manual annotation (93.5%). Conclusion We conclude that the proposed methods are suitable for automatic MER denoising and may help in the efficient elimination of undesirable signal artifacts. [ABSTRACT FROM AUTHOR]

Modern functional neurosurgery for movement disorders such as Parkinson's disease, tremor, and dystonia involves the placement of focal lesions or the application of deep brain stimulation (DBS) within circuits that modulate motor function. Precise targeting of these motor structures can be further refined by the use of electrophysiological approaches. In particular, microelectrode recordings enable the delineation of neuroanatomic structures. In the course of these operations, there is an opportunity not only to map basal ganglia structures but also to gain insights into how disturbances in neural activity produce movement disorders. In this review, we aim to highlight what the field has uncovered thus far about movement disorders through DBS. The work to date lays the foundation for future studies that will shed further light on dysfunctional circuits mediating diseases of the nervous system and how we might modulate these circuits therapeutically. [ABSTRACT FROM AUTHOR]

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300-9,000 Hz) and field potentials (3-100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson's disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms. NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms. [ABSTRACT FROM AUTHOR]

We describe a method for computing a pair of spike detection thresholds, called 'truncation thresholds', using truncated probability distributions, for extracellular recordings. In existing methods the threshold is usually set to a multiple of an estimate of the standard deviation of the noise in the recording, with the multiplication factor being chosen between 3 and 5 according to the researcher's preferences. Our method has the following advantages over these methods. First, because the standard deviation is usually estimated from the entire recording, which includes the spikes, it increases with firing rate. By contrast, truncation thresholds decrease in absolute value with increasing firing rate, thereby capturing more of the signal. Second, the parameters of the selected noise distribution are estimated more accurately by maximum likelihood fitting of the truncated distribution to the data delimited by the truncation thresholds. Third, the computation of the truncation thresholds is completely data-driven. It does not involve a userdefined multiplication factor. Fourth, methods that use a threshold that is proportional to the estimated standard deviation of the noise assume that the noise distribution is symmetrical around the mean. By contrast, truncation thresholds are not linked to each other by an assumption of symmetry about some axis. Fifth, existing methods do not verify that subthreshold data obey a noise distribution. Truncation thresholds, however, are defined by the fact that the distribution of the data they delimit is statistically indistinguishable, according to the Kolmogorov-Smirnov test, from a selected distribution, truncated at those thresholds. Application of the method is illustrated using recordings from cortical area M1 in awake behaving rats, as well as in simulated recordings. Source code and executables of a software suite that computes the truncation thresholds are provided for the case when the noise distribution is modeled as truncated normal. [ABSTRACT FROM AUTHOR]

Background: This report presents a case of medically refractory dystonia in a pediatric patient successfully treated with bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) while under general anesthesia by using microelectrode recordings (MERs) with intraoperative computed tomography (CT)., Observations: The patient was an 18-year-old female with primary dystonia secondary to mitochondrial Leigh syndrome. Her past medical history was significant for complex partial epilepsy and hearing loss treated with cochlear implants. Her cochlear implants precluded anatomical targeting via magnetic resonance imaging. Additionally, the patient could not tolerate awake surgery with MER. The decision was made to proceed with bilateral STN DBS with intraoperative CT with the patient under general anesthesia. The patient's cochlear implants made standard frame placement difficult, so navigation was performed with the Nexframe system. Recordings were obtained with the patient under general anesthesia with ketamine, dexmedetomidine, and remifentanil. At the 3- and 6-month follow-ups, the patient demonstrated marked improvement in dystonia without neurological complications., Lessons: This is the first case of dystonia secondary to Leigh syndrome treated with DBS. Additionally, the authors describe the novel use of the Nexframe for DBS lead placement in a pediatric patient. This demonstrates that STN DBS with the use of MER and intraoperative CT can be a safe and effective method of treating dystonia in certain pediatric patients.

Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains the most common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs), owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS) algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11-32Hz) and high frequency range (200-450Hz) were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA) method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square error of 1.22 mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11-32Hz) and the range of high frequency oscillations (200-450Hz) provided prediction accuracies of 72% and 68% respectively. The best prediction result obtained with monopolar LFP data was 68%. These results establish the initial evidence that LFPs can be strategically fused with computational intelligence in the operating room for STN localization and the selection of the track for chronic DBS electrode implantation.

Objective: To explore neurons with β oscillatory activity in the subthalamic nucleus (STN) in relation to parkinsonian motor signs.Methods: We studied 27 patients with Parkinson's disease (PD) who underwent electrode implantation for STN deep brain stimulation. Thirteen patients were classified as akinetic-rigid (AR) type and 14 patients were classified as mixed type. Microelectrode recording was performed in the STN and the electromyogram (EMG) was simultaneously recorded. Single-unit and spectral analyses were performed. Coherence analysis was used to explore the relationship between β oscillatory activity and EMG activity. Unpairedt-test and chi-square were used to compare the differences between the two PD types.Results: Of 130 neurons identified in the AR type, 43.8% were β oscillatory neurons (mean: 21.3 ± 6.87 Hz, βFB) and 0.8% were tremor frequency oscillatory neurons (4–6 Hz, TFB). Of 102 neurons identified in the mixed type, 19.6% were β oscillatory neurons and 26.5% were TFB oscillatory neurons. There was a significant difference in proportion of neurons with βFB and TFB oscillations between the two PD groups. Additionally, 12% of the βFB oscillatory neurons were coherent with limb EMG of the AR type, but there was no coherence in the mixed type. Most oscillatory neurons were localized in the dorsal portion of the STN.Conclusion: The STN βFB oscillatory neurons correlate with parkinsonian rigidity-bradykinesia. The high proportion of βFB oscillatory neurons found in the AR type of PD is indirect evidence for their importance in generating motor impairment. [ABSTRACT FROM AUTHOR]

Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains themost common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs), owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS) algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11-32Hz) and high frequency range (200-450Hz) were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA) method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square (RMS) error of 1.22mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11-32Hz) and the range of high frequency oscillations (200-450Hz) provided prediction accuracies of 72 and 68% respectively. The best prediction result obtained with monopolar LFP data was 68%. These results establish the initial evidence that LFPs can be strategically fused with computational intelligence in the operating room for STN localization and the selection of the track for chronic DBS electrode implantation. [ABSTRACT FROM AUTHOR]

Today, localization of the seizure focus heavily relies on EEG monitoring (scalp or intracranial). However, current technology enables much finer resolutions. The activity of hundreds of single neurons in the human brain can now be simultaneously explored before, during, and after a seizure or in association with an interictal discharge. This technology opens up new horizons to understanding epilepsy at a completely new level. This review therefore begins with a brief description of the basis of the technology, the microelectrodes, and the setup for their implantation in patients with epilepsy. Using these electrodes, recent studies provide novel insights into both the time domain and firing patterns of epileptic activity of single neurons. In the time domain, seizure-related activity may occur even minutes before seizure onset (in its current, EEG-based definition). Seizure-related neuronal interactions exhibit complex heterogeneous dynamics. In the seizure-onset zone, changes in firing patterns correlate with cell loss; in the penumbra, neurons maintain their spike stereotypy during a seizure. Hence, investigation of the extracellular electrical activity is expected to provide a better understanding of the mechanisms underlying the disease; it may, in the future, serve for a more accurate localization of the seizure focus; and it may also be employed to predict the occurrence of seizures prior to their behavioral manifestation in order to administer automatic therapeutic interventions. [ABSTRACT FROM AUTHOR]

Zusammenfassung Intraoperative Mikroelektrodenableitungen werden eingesetzt, um die Präzision funktionell-neurochirurgischer Eingriffe zu erhöhen. Ihr Haupteinsatzgebiet sind die gezielten Hirnoperationen im Rahmen der Tiefen Hirnstimulation zur Behandlung schwerer Bewegungsstörungen wie Morbus Parkinson, Dystonie oder therapierefraktärer Tremorformen. Dieser Artikel beschreibt die typischen elektrophysiologischen Befunde in den drei wichtigsten subkortikalen Zielgebieten in der funktionellen Neurochirurgie bei Bewegungsstörungen: Nucleus subthalamicus, Globus pallidus internus und Nucleus ventro-intermedius thalami. Intraoperative microelectrode recordings serve as an exploratory guide for many stereotactic neurosurgeons in order to objectively localize deep brain sites to be operated for the control of movement disorders. In this context, microelectrode recordings are used to (i) map structural boundaries, (ii) provide a physiologic delineation of the sensorimotor territory within the surgical target and (iii) to identify and localize neuronal activities related to pathologic brain function such as tremor or dystonia. This article provides an overview of discharge characteristics of single cell activity in the three most common targets for movement disorder surgery: subthalamic nucleus (STN), pars interna of the globus pallidus (GPi) and thalamic nucleus ventro-intermedius (Vim). [ABSTRACT FROM AUTHOR]