Marek Baláž

Participation of the subthalamic nucleus in executive functions: An intracerebral recording study

The objective of our work was to find whether the subthalamic nucleus (STN) is directly involved in cognitive activities, specifically in executive functions. Ten patients with idiopathic Parkinsons disease had P3 potentials recorded by externalized deep brain electrodes that were implanted in the STN or in its immediate vicinity. Two contacts of each electrode were positioned inside the STN according to clinical effect, perioperative microrecording, and stimulation. The P3 waves were recorded following the auditory stimulus in a standard oddball paradigm. They were compared with the P3 waves elicited from a protocol modified by a dual task with an increased demand on executive functions. The P3 potentials with a steep amplitude gradient evoked by the modified protocol were detected by the contacts in 8 of the 14 available electrodes, located either inside the STN or in its immediate vicinity. The modified protocol led to an increased latency of the P3 potential in 8 of 14 electrodes. No local field potentials of the standard P3 potentials were recorded. The P3 potentials related to the increased demand on executive functions were detected by the STN contacts known to have the best effect on Parkinsonian motor signs. This could suggest that the STN takes part in the executive function processing.

Cognitive event-related potentials and oscillations in the subthalamic nucleus.

Background: The cognitive role of the subthalamic nucleus (STN) remains largely unknown. Methods/Results: A modified protocol with a dual task elicited local field event-related potentials (ERPs) within the STN. No generators of ERPs were elicited by the standard oddball protocol in the STN (at variance with recordings from the putamen, caudate and pallidum). Repetitive transcranial magnetic stimulation (rTMS) over the right inferior frontal cortex caused a shortening of latencies of ERPs in standard and dual protocols. No changes were observable after the rTMS over the dorsolateral prefrontal cortex and sham stimulation. In the STN, only the tasks with an increased demand on executive functions produced the α-/β-event-related desynchronization/synchronization in visuomotor tasks with single letters writing. Conclusion: Our results indicate a specific, task-related involvement of the STN in the cognitive activities. Cognitive processing in the STN is possibly processed via hyperdirect cortico-STN pathway. Certain effects of deep brain stimulation surgery on cognitive performance could be explained by a direct effect on ‘cognitive’ parts of the STN.

Involvement of the subthalamic nucleus in cognitive functions — A concept ☆

The involvement of the subthalamic nucleus (STN) in a broad spectrum of various non-motor functions - attention, executive functions, verbal learning and memory, verbal abstract reasoning, conflict resolution, and emotions - has been reported. The STN has an anatomically central position within the basal ganglia(BG)-thalamocortical motor, associative and limbic circuits. The STN might interfere with non-motor functions as an indirect modulator rather than a regulator. Mechanisms modulating the motor and non-motor functions might differ. The STN has been implicated in control of non-motor behaviors via the tuning of specific circuits depending on the task. The STN might modulate selected non-motor functions via contextual modulation of certain cortical areas. Based on intracerebral recordings, we proposed that the non-motor activities in the BG are organized in some way other than the well-known organization of the cortico-BG-thalamocortical circuits. These findings support the hypothesis of a cortico-STN bypass of the BG-thalamocortical circuitry under some circumstances. The exact role of the STN and the BG in non-motor functions remains an important and interesting challenge for future research.

The role of brain shift, patient age, and Parkinson's disease duration in the difference between anatomical and electrophysiological targets for subthalamic stimulation

Abstract Introduction. Although microrecording is common in subthalamic stimulation, microelectrode monitoring prolongs surgical time and may increase the risk of haemorrhagic complications. The main reason for electrophysiological mapping is the discrepancy between the calculated anatomical and final electrophysiological targets. The aim of this paper is to describe the relationship between anatomical and electrophysiological targets defined as the best electrophysiological recordings from multiple parallel electrode tracts, explaining the target discrepancy with attention paid to the role of brain shift and patient- and disease-related factors. Materials and methods. Subthalamic electrodes were stereotactically implanted in 58 patients using microrecording by means of parallel electrodes at defined distances. The relationship between the final electrode placement to its anatomical trajectory and the relationship between the definitive electrodes implanted on the right and left sides were analysed, as was the influence of patient age, Parkinsons disease duration, and late motor complications duration. Results. Final electrode placement matched the anatomical trajectory in 53.4% of patients on the right side and 43.1% of patients on the left side. Electrode positions were symmetrical in 38.3% of patients. The analysis of left and right electrode positions does not prove a statistically significant prevalence of lateral and posterior final electrode trajectories as could be expected from lateral and posterior movements of the brain caused by brain shift, although there was some tendency for a larger percentage of lateral electrodes on the left side. Age, Parkinsons disease duration, and L-DOPA effect duration were not confirmed as responsible factors. Conclusions. The difference between anatomical trajectory and final electrode placement supports the use of functional microelectrode monitoring in subthalamic deep brain stimulation. Brain shift is not the only causative factor of the difference. The possible roles of age, Parkinsons disease duration, and late motor complications duration were also not confirmed by study results.

High-Frequency Oscillations in the Human Anterior Nucleus of the Thalamus

Deep brain stimulation of the anterior nucleus of the thalamus (ANT- DBS) has recently been introduced in therapy for refractory epilepsy and is approved for clinical use in Europe. ANT is a part of the Papez circuitry and is a key structure in the intrathalamic pathways; it also projects to the cingulate gyrus and further to the limbic structures and wide regions of the neocortex, and via the mammillary circuit to the brain stem. ANT stimulation produces EEG changes in the frontal and temporal areas and inhibits seizures. The role played by the ANT in human epileptic seizures and the mechanisms leading to the anti- seizure effects of ANT-DBS have not yet been fully elucidated. Knowledge of processes occurring in the ANT in human epilepsy might improve the understanding of its role. Here we report the first description of interictal and ictal EEG recording in the human ANT.

Complex motor-cognitive factors processed in the anterior nucleus of the thalamus: an intracerebral recording study.

Abstract Cognitive adverse effects were reported after the deep brain stimulation (DBS) of the anterior nucleus of the thalamus (AN) in epilepsy. As the AN may have an influence on widespread neocortical networks, we hypothesized that the AN, in addition to its participation in memory processing, may also participate in cognitive activities linked with the frontal neocortical structures. The aim of this study was to investigate whether the AN might participate in complex motor–cognitive activities. Three pharmacoresistant epilepsy patients implanted with AN–DBS electrodes performed two tasks involving the writing of single letters: (1) copying letters from a monitor; and (2) writing of any letter other than that appearing on the monitor. The cognitive load of the second task was increased. The task-related oscillatory changes and evoked potentials were assessed. Local event-related alpha and beta desynchronization were more expressed during the second task while the lower gamma synchronization decreased. The local field event-related potentials were elicited by the two tasks without any specific differences. The AN participates in cognitive networks processing complex motor–cognitive tasks. Attention should be paid to executive functions in subjects undergoing AN–DBS.

Factors responsible for early postoperative mental alterations after bilateral implantation of subthalamic electrodes.

Abstract Introduction: Early postoperative mental changes are the most frequent problem after bilateral subthalamic electrode implantation. The study aims to find an association between them and factors related to patient, disease and surgery, including the size of the third ventricle as brain atrophy marker. Material and methods: The study included 80 patients with bilateral subthalamic electrodes implanted for motor complications of Parkinson’s disease (PD). Patients’ age, disease and motor complications duration, medication, neuropsychological tests, surgical reports, third ventricle length (intercommissural distance) and width (intermammillary distance) were analysed. Results: Early mental alterations requiring treatment were observed in 25.0% of patients with higher age being significant predictor. The duration of PD motor complications, L DOPA equivalent dose, DSR Mattis, third ventricle length and width were not statistically significant predictors. The incidence of postoperative mental alteration with intermammillary distance > 8 mm was 60%. The percentage of left sided electrodes implanted in anterior trajectory is significantly higher in patients with early mental changes. Conclusions: Higher age is a risk factor for early postoperative mental changes, but not disease, late motor complications duration and parameters describing third ventricular size except the excessive intermammillary distance. Left sided electrode implanted in anterior position is a risk factor.

Learning curve in anatomo-electrophysiological correlations in subthalamic nucleus stimulation.

AIM Advances in neuroradiological planning techniques in deep brain stimulation have put the need for intraoperative electrophysiological monitoring into doubt. Moreover intraoperative monitoring prolongs surgical time and there is potential association between the use of microelectrodes and increased incidence of hemorrhagic complications. The aim of this study was to analyze the correlation between the anatomically planned trajectory and the final subthalamic electrode placement after electrophysiological monitoring in patients with Parkinsons disease and its change with the increasing experience of the surgical team. MATERIAL AND METHODS The trajectories of right (first implanted) and left electrodes were compared in the first 50 patients operated on (Group 1) and the next 50 patients (Group 2). RESULTS In Group 1, 52% of central trajectories were on the right and 38% on the left; in Group 2, the percentage of central trajectories was 76% on the right and 78% on the left; the difference was statistically significant (p=0.021 and 0.001). The difference in the percentage of posterior trajectories reflecting brain shift between the right and left sides was statistically insignificant in Groups 1 (26% and 28%, p=0.999) and 2 (18% and 12%, p=0.549). The percentage of bilateral central electrodes was 14% and 62% in Groups 1 and 2, respectively. CONCLUSION The correlation between anatomically planned trajectory and final electrode placement markedly improves with the number of patients. However the significant percentage of patients with final electrode trajectory differing from anatomically planned target supports the use of intraoperative monitoring.

Preoperative Visual Memory Performance as a Predictive Factor of Cognitive Changes after Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease

Aim: Deep brain stimulation of subthalamic nucleus (DBS STN) is considered to be a clinically established treatment method to manage the symptoms of advanced stage Parkinson’s disease. Despite the strict inclusion criteria, it may have negative impact on the quality of cognitive functions. Our research aimed to identify predictive neuropsychological factors that signal risk of postoperative deterioration of cognitive functions before the DBS STN. Patients and methods: Forty-six patients with idiopathic Parkinson’s disease were included in the study (mean age at the time of operation 59.61 years; SD = 7.06). The patients were examined by a neuropsychologist before and after the DBS STN implantation. The neuropsychological test battery included Wechsler Adult Intelligence Scale short form, Mattis Dementia Rating Scale, Word list, Rey-Osterrieth Complex Figure Test, Stroop Colour Word Test and verbal fluency tests. Results: The quality of visual memory proved to be a sensitive predictive factor related to risk of cognitive changes after DBS STN implantation, as before the implantation the level of visual memory statistically negatively corresponded to impairment of cognitive performance in neuropsychological tests after the implantation. Conclusion: Low performance in the area of visual memory before the implantation may predict an increased risk of cognitive deterioration after the implantation of DBS STN in Parkinson’s disease. We assume that the changes in visual memory reflect progression of degenerative process in Parkinson’s disease into other brain areas away from the frontostriatal circuit, mainly to posterior temporoparietal areas.

Long-Term Treatment of Focal Dystonias (Cervical and Writer’s Cramp): Clinical and Quality of Life Impact

Dystonias are a group of disorders with many different clinical manifestations but with certain common features. Affected patients share involuntary sustained or intermittent muscle contractions that cause abnormal postures and/or repetitive movements. The most common forms of adult-onset focal dystonias are cervical dystonia, blepharospasm, oromandibular dystonia, laryngeal dystonia, and limb dystonias such as writer’s cramp. In this chapter, we were interested in certain aspects of the long-term treatment of two focal dystonias, cervical dystonia and limb dystonia (writer’s cramp), with botulinum toxin A (BoNT-A).