Modulation of neuronal activity in human centromedian nucleus during an auditory attention and working memory task.

Centromedian nucleus (CM) is one of several intralaminar nuclei of the thalamus and is thought to be involved in consciousness, arousal, and attention. CM has been suggested to play a key role in the control of attention, by regulating the flow of information to different brain regions such as the ascending reticular system, basal ganglia, and cortex. While the neurophysiology of attention in visual and auditory systems has been studied in animal models, combined single unit and LFP recordings in human have not, to our knowledge, been reported. Here, we recorded neuronal activity in the CM nucleus in 11 patients prior to insertion of deep brain stimulation electrodes for the treatment of epilepsy while subjects performed an auditory attention task. Patients were requested to attend and count the infrequent (p = 0.2) odd or "deviant" tones, ignore the frequent standard tones and report the total number of deviant tones at trial completion. Spikes were discriminated, and LFPs were band pass filtered (5-45 Hz). Average peri­stimulus time histograms and spectra were constructed by aligning on tone onsets and statistically compared. The firing rate of CM neurons showed selective, multi-phasic responses to deviant tones in 81% of the tested neurons. Local field potential analysis showed selective beta and low gamma (13-45 Hz) modulations in response to deviant tones, also in a multi-phasic pattern. The current study demonstrates that CM neurons are under top-down control and participate in the selective processing during auditory attention and working memory. These results, taken together, implicate the CM in selective auditory attention and working memory and support a role of beta and low gamma oscillatory activity in cognitive processes. It also has potential implications for DBS therapy for epilepsy and non-motor symptoms of PD, such as apathy and other disorders of attention.

Persistence of Basal Ganglia Oscillatory Activity During Tremor Attenuation by Movement in Parkinson's Disease Patients.

BACKGROUND: One of the characteristics of parkinsonian tremor is that its amplitude decreases with movement. Current models suggest an interaction between basal ganglia (BG) and cerebello-thalamo-cortical circuits in parkinsonian tremor pathophysiology. OBJECTIVE: We aimed to correlate central oscillation in the BG with electromyographic activity during re-emergent tremor in order to detect changes in BG oscillatory activity when tremor is attenuated by movement. METHODS: We performed a prospective, observational study on consecutive parkinsonian patients who underwent deep brain stimulation surgery and presented re-emergent tremor. Coherence analysis between subthalamic nucleus/globus pallidus internus (STN/GPi) tremorous activity measured by microrecording (MER) and electromyogram (EMG) from flexor and extensor wrist muscles during rest, posture, and re-emergent tremor pause was performed during surgery. The statistical significance level of the MER-EMG coherence was determined using surrogate data analysis, and the directionality of information transfer between BG and muscle was performed using entropy transfer analysis. RESULTS: We analyzed 148 MERs with tremor-like activity from 6 patients which were evaluated against the simultaneous EMGs, resulting in 296 correlations. Of these, 26 presented a significant level of coherence at tremor frequency, throughout rest and posture, with a complete EMG stop in between. During the pause, all recordings showed sustained MER peaks at tremor frequency (±1.5 Hz). Information flows preferentially from BG to muscle during rest and posture, with a loss of directionality during the pause. CONCLUSIONS: Our results suggest that oscillatory activity in STN/GPi functionally linked to tremor sustains firing frequency during re-emergent tremor pause, thus suggesting no direct role of the BG circuit on tremor attenuation due to voluntary movements. © 2024 International Parkinson and Movement Disorder Society.

Beta band oscillations in the motor thalamus are modulated by visuomotor coordination in essential tremor patients.

Introduction: Beta oscillations in sensorimotor structures contribute to the planning, sequencing, and stopping of movements, functions that are typically associated with the role of the basal ganglia. The presence of beta oscillations (13-30 Hz) in the cerebellar zone of the thalamus (the ventral intermediate nucleus - Vim) indicates that this rhythm may also be involved in cerebellar functions such as motor learning and visuomotor adaptation. Methods: To investigate the possible role of Vim beta oscillations in visuomotor coordination, we recorded local field potential (LFP) and multiunit activity from the Vim of essential tremor (ET) patients during neurosurgery for the implantation of deep brain stimulation (DBS) electrodes. Using a computer, patients performed a visuomotor adaptation task that required coordinating center-out movements with incongruent visual feedback imposed by inversion of the computer display. Results: The results show that, in ET, Vim beta oscillations of the LFP were lower during the incongruent center-out task than during the congruent orientation. Vim firing rates increased significantly during periods of low beta power, particularly on approach to the peripheral target. In contrast, beta power in the subthalamic nucleus of Parkinson's disease (PD) patients did not differ significantly between the incongruent and the congruent orientation of the center-out task. Discussion: The findings support the hypothesis that beta oscillations of the Vim are modulated by novel visuomotor tasks. The inverse relationship between the power of Vim-LFP beta oscillations and Vim firing rates suggest that the suppression of beta oscillations may facilitate information throughput to the thalamocortical circuit by modulation of Vim firing rates.

Long-term follow-up of Parkinsonian patients operated on with deep brain electromodulation without intraoperative microrecording.

Background: Deep brain electromodulation (DBEM), also known as deep brain stimulation in different intracerebral targets, is the most widely used surgical treatment due to its effects in reducing motor symptoms of Parkinson's disease. The intracerebral microelectrode recording has been considered for decades as a necessary tool for the success of Parkinson's surgery. However, some publications give more importance to intracerebral stimulation as a better predictive test. Since 2002, we initiated a technique of brain implant of electrodes without micro recording and based solely on image-guided stereotaxis followed by intraoperative macrostimulation. In this work, we analyze our long-term results, taking into account motor skills and quality of life (QL) before and after surgery, and we also establish the patient's time of clinical improvement. Methods: This is a descriptive clinical study in which the motor state of the patients was evaluated with the unified Parkinson's disease scale (UPDRS) and the QL using the Parkinson's disease QL questionnaire 39 questionnaires before surgery, in the "on" state of the medication; and after surgery, under active stimulation and in the "on" state. Results: Twenty-four patients with ages ranging from 37 to 78 years undergoing surgery DBEM on the subthalamic nucleus were studied. An improvement of 41.4% in motor skills and 41.7% in QL was obtained. Conclusion: When microrecording is not available, the results that can be obtained, based on preoperative imaging and clinical intraoperative findings, are optimal and beneficial for patients.

Placement accuracy of the second electrode in bilateral deep brain stimulation surgery.

PURPOSE: Due to brain shift during bilateral deep brain stimulation (DBS) surgery, placement of the second electrode may be subjected to more error than that of the first electrode. The authors aimed to investigate the accuracy of second electrode placement in this setting. MATERIALS AND METHODS: Fifty-five patients with Parkinson's disease who underwent bilateral DBS surgery (110 electrodes) were retrospectively evaluated. The targets were subthalamic nucleus (STN) and globus pallidus interna (GPi) in 40 and 15 cases, respectively. Preoperative planning and postoperative electrode images were co-registered to compare the error margin between the two sides. RESULTS: There is a statistically significant difference in the directional axis error along the y axis only when comparing each laterality (posterior 0.04 ± 1.21 mm vs anterior 0.41 ± 1.07 mm, p = 0.006). There is no significant difference of other error parameters, final track location, and number of microelectrode recording passes between the two sides. In a subgroup analysis, there is a significant difference in directional axis error along the y axis only in the STN subgroup (posterior 0.40 ± 1.05 mm vs anterior 0.18 ± 1.04 mm, p = 0.003). CONCLUSION: Although a statistically significant difference in directional axis error along the y axis was found between first and second electrode placements in the STN group but not in the GPi group, its magnitude is well below the clinically significant threshold.

Thalamic anterior part of the ventral posterolateral nucleus and central lateral nucleus in the genesis of central post-stroke pain.

BACKGROUND: The genesis of central post-stroke pain (CPSP) is important but difficult to understand. We evaluated the involvement of the thalamic anterior part of the ventral posterolateral nucleus (VPLa) and central lateral nucleus (CL) in the occurrence of CPSP. METHOD: Stereotactic thalamotomy was performed on the posterior part of the ventral lateral nucleus (VLp)-VPLa and CL in 9 patients with CPSP caused by deep-seated intracerebral hemorrhage. Computed tomography (CT) did not reveal definite thalamic lesion in 5 patients but did in 4 patients. Electrophysiological studies of these thalamic nuclei were carried out during the surgery. Anatomical studies using CT were performed in another 20 patients with thalamic hemorrhage who had clear consciousness but had sensory disturbance at onset. RESULTS: Neural activities were preserved and hyperactive and unstable discharges (HUDs) were often recognized along the trajectory in the thalamic VLp-VPLa in 5 patients without thalamic lesion. Surgical modification of this area ameliorated pain, particularly movement-related pain. Neural activities were hypoactive in the other 4 patients with thalamic lesion. However, neural activities were preserved and HUDs were sometimes recognized in the CL. Sensory responses were seen, but at low rate, in the sensory thalamus. Anatomical study showed that the thalamic lesion was obviously smaller in the patients with developing pain in the chronic stage. CONCLUSIONS: Change in neural activities around the cerebrovascular disease lesion in the thalamic VPLa or CL might affect the perception of sensory impulses or sensory processing in those thalamic nuclei, resulting in the genesis of CPSP.

Electrical Thalamic Stimulation in the Anterior Part of the Ventral Posterolateral Nucleus for the Treatment of Patients With Central Poststroke Pain.

OBJECTIVES: The effects of thalamic stimulation of the anterior part of the ventral posterolateral nucleus (VPLa) for central poststroke pain (CPSP) and the pain-related electrophysiological characteristics of this structure were investigated. MATERIALS AND METHODS: Nine patients with CPSP manifesting as hemibody pain were enrolled. Stereotactic thalamic VPLa stimulation was implemented, and intraoperative electrophysiological studies on hyperactive and unstable discharges (HUDs) and responses to sensory and electrical stimulation were performed in the sensory thalamus. A preoperative somatosensory-evoked potential (SEP) study was carried out in all nine patients and in eight other patients with localized pain. RESULTS: The patients were classified into two groups: a HUD-dominant group (group H, n = 5) and a sensory response-dominant group (group R, n = 4). HUDs were frequently encountered in the thalamic VPLa in the former group. The total number of HUDs and the number along the trajectory to the VPLa in group H were significantly larger than those in group R. The improvements on the pain numeric rating scale in group H were significantly higher than those in group R two years after surgery. The amplitude ratio of the SEP N20s in the ipsilateral to the contralateral side of CVD lesion in the study group was significantly lower than in the localized pain group. CONCLUSIONS: Adequate and stable pain relief with thalamic VPLa stimulation is obtainable in patients with CPSP who exhibit hyperactivity and electrical instability along the trajectory to this nucleus. Both responders and nonresponders were found to have severe dysfunction of the lemniscal system.

A Case Report of Multitrack Recording of Posterior Subthalamic Nucleus, Caudal Zona Incerta, and Prelemniscal Radiation: Which Is Most Effective for Bradykinesia?

Deep brain stimulation (DBS) of the posterior subthalamic nucleus (pSTN), caudal zona incerta (cZI), and prelemniscal radiation (Raprl) has been shown to improve Parkinsonian motor symptoms. We herein report neurophysiological and functional differences among the cZI, Raprl, and pSTN in a 68-year-old male patient with Parkinson's disease (PD). The stereotactic implantation of DBS electrodes in the right STN was performed. Thereafter, a transfrontal trajectory for the left cZI was planned for left side implantation, with the expectation that the electrode entered the pSTN in the case of a posterior brain shift. In the implantation of the DBS lead in the cZI, three microelectrodes were simultaneously placed in an array with the central, medial, and anterior positions placed 2 mm apart to delineate the cZI, Raprl, and pSTN, respectively. A maximal reduction in bradykinesia was obtained from the stimulation of the pSTN at the lowest voltage thresholds, and the voltage threshold for abolishing tremors was lower in the Raprl and cZI than in the pSTN. The left DBS lead was implanted in the pSTN because right-sided bradykinesia was more severe than tremor. The multitrack recording of cZI, Raprl, and pSTN might broaden target selection depending on patients' symptoms.

Stereotactic Selective Thalamotomy for Focal Dystonia with Aid of Depth Microrecording.

OBJECTIVE: Long-term effectiveness of selective ventralis intermedius nucleus (VIM)-ventralis oralis nucleus (VO) thalamotomy with depth microrecording for the treatment of focal dystonia was evaluated. The optimal thalamic areas for controlling focal dystonia were studied based on the electrophysiologic and anatomic data. METHODS: Stereotactic selective VIM-VO thalamotomy with depth microrecording was carried out in 8 patients with focal arm and hand dystonia and in 1 patient with cervical dystonia. Electrophysiologic data on the lateral part of thalamic VIM were studied in patients with focal dystonia. A very small and narrow therapeutic lesion was formed in the shape of a square on the sagittal plane and of an I, rotated V, Y, or inverse Y on the axial plane in the VIM-VO, which covered the kinesthetic response area topographically related to focal dystonia. Patients with arm and hand dystonia were followed up for 4.7 ± 3.0 years and 1 patient with cervical dystonia was followed up for 18.2 years. RESULTS: Marked improvement of focal dystonia was shown by functional assessment using the Unified Dystonia Rating Scale. Transient dysarthria was recognized in 1 patient. The sequence of body localization of kinesthetic response in the VIM was clearly shown in patients with focal dystonia. Decreases in the amplitude and amplitude ratio of electromyography on the forearm muscles were markedly significant after VIM thalamotomy, but insignificant after VO thalamotomy immediately after VIM thalamotomy. CONCLUSIONS: Marked reduction of electromyographic tonic discharges of focal dystonia was shown after VIM lesioning. Selective VIM-VO thalamotomy showed good and long-term stable effects for focal dystonia.

Superselective Thalamotomy in the Most Lateral Part of the Ventralis Intermedius Nucleus for Controlling Essential and Parkinsonian Tremor.

OBJECTIVE: The minimum and essential thalamic areas for reducing tremor were investigated in cases treated by superselective thalamotomy in the most lateral part of the ventralis intermedius nucleus (mlp-VIM). METHODS: Stereotactic superselective VIM thalamotomy with depth microrecording was performed in 21 patients with essential tremor (ET) and 15 patients with tremor-dominant Parkinson disease (PD). A very small and narrow (axial plane) therapeutic lesion was formed as a square on the sagittal plane and inverse V on the axial plane in the mlp-VIM, which covered the kinesthetic response area topographically related to tremor. Patients with ET were followed up for 4.7 ± 3.0 years and patients with PD for 7.9 ± 3.9 years. RESULTS: Almost complete tremor control was achieved in all patients immediately after surgery and continued for up to 8 years. A few adverse events were recognized but disappeared within 1 month without 1 patient with thalamic hemorrhage. The medial border of the therapeutic lesion was significantly more lateral in both patients with ET and patients with PD than the calculated standard target point and was in patients with PD than in patients with ET. The mean width was only about 2.4 mm. The individual differences of the adequate location of the therapeutic lesion were significantly greater in the ET than in the PD group. CONCLUSIONS: The important area for reducing tremor was small and narrow and was located in the mlp-VIM, where the proprioceptive ascending signals from the tremor-dominant body part are conducted. Superselective thalamotomy in the mlp-VIM was safe and effective for the long-term in patients with ET and PD.

The advances of Deep Brain Stimulation (DBS) for treatment of Parkinson's disease (PD)

Advanced Parkinson's disease (PD) is characterized by the presence of motor fluctuations, various degrees of dyskinesia, and disability with functional impact on daily living and independence. Therapeutic management aims to extend levodopa (L-DOPA) benefit while minimizing motor complications and includes, in selected cases, the implementation of drug infusion and surgical techniques. The concept of deep brain stimulation (DBS) for PD was introduced over 20 years ago, but our understanding of the nuances of this procedure continues to improve. This review aims to demonstrate the advances of DBS in the treatment of PD patients. (AU)

Microrecording and image-guided stereotactic biopsy of deep-seated brain tumors.

OBJECT: Image-guided stereotactic brain tumor biopsy cannot easily obtain samples of small deep-seated tumor or selectively sample the most viable region of malignant tumor. Image-guided stereotactic biopsy in combination with depth microrecording was evaluated to solve such problems. METHODS: Operative records, MRI findings, and pathological specimens were evaluated in 12 patients with small deep-seated brain tumor, in which image-guided stereotactic biopsy was performed with the aid of depth microrecording. The tumors were located in the caudate nucleus (1 patient), thalamus (7 patients), midbrain (2 patients), and cortex (2 patients). Surgery was performed with a frameless stereotactic system in 3 patients and with a frame-based stereotactic system in 9 patients. Microrecording was performed to study the electrical activities along the trajectory in the deep brain structures and the tumor. The correlations were studied between the electrophysiological, MRI, and pathological findings. Thirty-two patients with surface or large brain tumor were also studied, in whom image-guided stereotactic biopsy without microrecording was performed. RESULTS: The diagnostic yield in the group with microrecording was 100% (low-grade glioma 4, high-grade glioma 4, diffuse large B-cell lymphoma 3, and germinoma 1), which was comparable to 93.8% in the group without microrecording. The postoperative complication rate was as low as that of the conventional image-guided method without using microelectrode recording, and the mortality rate was 0%, although the target lesions were small and deep-seated in all cases. Depth microrecording revealed disappearance of neural activity in the tumor regardless of the tumor type. Neural activity began to decrease from 6.3 ± 4.5 mm (mean ± SD) above the point of complete disappearance along the trajectory. Burst discharges were observed in 6 of the 12 cases, from 3 ± 1.4 mm above the point of decrease of neural activity. Injury discharges were often found at 0.5-1 mm along the trajectory between the area of decreased and disappeared neural activity. Close correlations between electrophysiological, MRI, and histological findings could be found in some cases. CONCLUSIONS: Image-guided stereotactic biopsy performed using depth microrecording was safe, it provided accurate positional information in real time, and it could distinguish the tumor from brain structures during surgery. Moreover, this technique has potential for studying the epileptogenicity of the brain tumor.

Subtalamotomía bilateral diferida guiada por microrregistros. Resultados motores a un año / Bilateral delayed subtalamotomy guided by micro-records. One-year motor results

Introducción: diferentes técnicas quirúrgicas representan una alternativa para el tratamiento de la enfermedad de Parkinson avanzada (EP). El gran desarrollo en las últimas décadas de modernas técnicas de imágenes sumado a los avances del registro neurofisiológico nos permiten localizar y generar lesiones en forma precisa, con bajo número de complicaciones y excelentes resultados funcionales. Objetivo: Describir los resultados motores obtenidos a los 12 meses post-operatorios de pacientes con diagnóstico de EP avanzada sometidos a subtalamotomía bilateral diferida guiada por microrregistro. Material y Métodos: Se seleccionaron 9 pacientes con diagnóstico de EP avanzada de acuerdo a los criterios de la United Kingdom Parkinson´s Disease Brain Bank, evaluando los efectos de la subtalamotomía bilateral en dos tiempos quirúrgicos. Resultados: Una marcada mejoría de los síntomas cardinales como rigidez, bradicinesia y temblor se observó en todos los pacientes, fundamentalmente en la condición de “off”, y en menor medida también en condición “on”. Se destaca un significativo control de las fluctuaciones motoras y discinesias. Conclusión: La subtalamotomía bilateral diferida guiada por microregistro es un método útil y efectivo en el tratamiento de los síntomas motores de la Enfermedad de Parkinson.

Introduction: in the treatment of advanced Parkinson´s disease (PD) there are different surgical techniques that represent a valid alternative. The development of modern images techniques and neurofisiological recording allow us to generate accurate lesions, with low complications and excellent functional results. Objective: Describe motor results 12 months post-surgical of patients with advanced PD submitted to bilateral and deferred subthalamotomy guided by microrecording. Material and Methods: We selected 9 patients with advanced PD diagnosis in concordance with United Kingdom Parkinson`s Disease Brain Bank criteria, evaluating the effects of bilateral subthalamotomy in two different surgical steps. Results: A marked improvement of cardinal symptoms such as rigidity, bradykinesia and tremor was observed in all patients, fundamentally in “off” condition, and lesser extent in “on” condition. We highlighted a significant control of motor fluctuations and dyskinesias. Conclusion: Bilateral and deferred suthalamotomy guided by microrecording is an effective and useful method in treatment of cardinal motor symptoms of PD.

Pallidotomy Guided by MRI and Microrecording for Parkinson's Disease

OBJECTIVE: The exact position of the lesion during the pallidotomy is critical to obtain the clinical improvement of parkinson's disease without damage to surrounding structure. Ventriculogrphy, CT(computed tomograpy) or MRI(magnetic resonance imaging) have been used to determine the initial coordinates of stereotactic target for pallidotomy. The goal of this study was to determine whether microelectrode recording significantly improves the neurophysiologic localization of the target obtained from MRI. METHODS: Twenty patients were studied. They underwent a unilateral pallidotomy. Leksell frame was applied and T1 axial images parallel to the AC-PC(anterior commissure-posterior commissure) plane using a 1.5 Tesla MRI with 3mm slice thickness were obtained. Anteroposterior coordinate of target was chosen at 2mm in front of the midcommissural point and lateral coordinate between 19 and 22mm from the midline. The vertical coordinate was calculated on coronal slice using a fast spin echo inversion recovery sequence(FSEIR) related to the position of the choroidal fissure and ranged over 4-5mm below the AC-PC plane. Confirmation of the anatomical target was done on axial slices using the same FSEIR sequence. Microrecording was done at the pallidum contralateral to the symptomatic side using an electrode with a tip diameter of 1nm diameter tip and 1.1-1.4 mOhm impedance at 1000Hz. Electrophysiologic localization of the target was also confirmed intraoperatively by macrostimulation. RESULTS: Microrecording techniques were reliable to define the transition from the base of the pallidum which was characterized by the disappearance of spike activity and by the change of the audible background activity. Signals from high amplitude neurons firing at 200-400Hz were recorded in the pallidal base. X, Y and Z coordinates of target obtained from the MRI were within 1mm from the X, Y, Z coordinates obtained with microrecording in 16 patients (80%), 15 patients(75%), 10 patients(50%) respectively. The difference of Y coordinate between on MRI and on microrecording was 4mm in only one patient. CONCLUSION: The MRI was accurate to localize the target within 1mm of the error from microrecording target in 70% of the patients. 4mm discrepancy was observed only once. We conclude that MRI alone can be used to determine the target for pallidotomy in most patients. However, microrecording technique can still be extremely valuable in patents with aberrant anatomy or unusual MRI coordinates. We also consider physiologic confirmation of the target using macrostimulation to be mandatory in all cases.