Mapping of subthalamic nucleus using microelectrode recordings during deep brain stimulation

Alongside stereotactic magnetic resonance imaging, microelectrode recording (MER) is frequently used during the deep brain stimulation (DBS) surgery for optimal target localization. The aim of this study is to optimize subthalamic nucleus (STN) mapping using MER analytical patterns. 16 patients underwent bilateral STN-DBS. MER was performed simultaneously for 5 microelectrodes in a setting of Ben's-gun pattern in awake patients. Using spikes and background activity several different parameters and their spectral estimates in various frequency bands including low frequency (2-7 Hz), Alpha (8-12 Hz), Beta (sub-divided as Low_Beta (13-20 Hz) and High_Beta (21-30 Hz)) and Gamma (31 to 49 Hz) were computed. The optimal STN lead placement with the most optimal clinical effect/ side-effect ratio accorded to the maximum spike rate in 85% of the implantation. Mean amplitude of background activity in the low beta frequency range was corresponding to right depth in 85% and right location in 94% of the implantation respectively. MER can be used for STN mapping and intraoperative decisions for the implantation of DBS electrode leads with a high accuracy. Spiking and background activity in the beta range are the most promising independent parameters for the delimitation of the proper anatomical site

An AI-supported diagnostic tool for obstructive sleep apnea patients based on delta-alpha connectivity at the sensorimotor cortex [Abstract]

Background: The modulation of delta-alpha phase-amplitude cross-frequency coupling (PACFC) may influence information processing throughout the human cerebral cortex. We investigated whether this frequency band-specific modulation is impaired in patients with obstructive sleep apnea (OSA). Patients & Methods: In this study, the C3- and C4- electroencephalographic recordings of 170 participants (86 in main dataset: age 27-84 years, 44 subjects had moderate or severe OSA with respiratory disturbance index RDI>15/h; 84 in validation dataset: age 35 -75 years, 42 subjects with RDI>15/h) who underwent full-night polysomnography (PSG) were evaluated. We tested if the delta-alpha PACFC modulation index (MI) at the sensorimotor cortex differs between OSA patients with RDI>15/h and those with RDI≤15/h in distinct sleep stages. Further, by making use of a Support Vector Machine (SVM) algorithm, we tested if the sleep stage – specific MIs could predict RDI values of OSA patients. Results: In both datasets, in OSA patients with RDI >15/h, the delta-alpha CFC-MI was significantly (p< 0.05) reduced at the sensorimotor cortex during REM and NREM1 stages, while increased during NREM2 compared to patients with RDI ≤15/h. In addition, the delta-alpha MI in REM sleep stage could provide with use of an SVM algorithm a quite reliable (82% accuracy) prediction of the RDI in OSA patients. Conclusions: This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep further supports the concept of a cortical sensorimotor dysfunction in OSA patients. Additionally, the delta – alpha MI during REM sleep may provide an objective neurophysiologic surrogate marker of respiratory distress in OSA patients

Covarying patterns of white matter lesions and cortical atrophy predict progression in early MS

Objective We applied longitudinal 3T MRI and advanced computational models in 2 independent cohorts of patients with early MS to investigate how white matter (WM) lesion distribution and cortical atrophy topographically interrelate and affect functional disability. Methods Clinical disability was measured using the Expanded Disability Status Scale Score at baseline and at 1-year follow-up in a cohort of 119 patients with early relapsing-remitting MS and in a replication cohort of 81 patients. Covarying patterns of cortical atrophy and baseline lesion distribution were extracted by parallel independent component analysis. Predictive power of covarying patterns for disability progression was tested by receiver operating characteristic analysis at the group level and support vector machine for individual patient outcome. Results In the study cohort, we identified 3 distinct distribution types of WM lesions (cerebellar, bihemispheric, and left lateralized) that were associated with characteristic cortical atrophy distributions. The cerebellar and left-lateralized patterns were reproducibly detected in the second cohort. Each of the patterns predicted to different extents, short-term disability progression, whereas the cerebellar pattern was associated with the highest risk of clinical worsening, predicting individual disability progression with an accuracy of 88% (study cohort) and 89% (replication cohort), respectively. Conclusion These findings highlight the role of distinct spatial distribution of cortical atrophy and WM lesions predicting disability. The cerebellar involvement is shown as a key determinant of rapid clinical deterioration

Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical Applications in Parkinson's Disease

L-DOPA is still the most effective pharmacological therapy for the treatment of motor symptoms in Parkinson's disease (PD) almost four decades after it was first used. Deep brain stimulation (DBS) is a safe and highly effective treatment option in patients with PD. Even though a clear understanding of the mechanisms of both treatment methods is yet to be obtained, the combination of both treatments is the most effective standard evidenced-based therapy to date. Recent studies have demonstrated that DBS is a therapy option even in the early course of the disease, when first complications arise despite a rigorous adjustment of the pharmacological treatment. The unique feature of this therapeutic approach is the ability to preferentially modulate specific brain networks through the choice of stimulation site. The clinical effects have been unequivocally confirmed in recent studies; however, the impact of DBS and the supplementary effect of L-DOPA on the neuronal network are not yet fully understood. In this review, we present emerging data on the presumable mechanisms of DBS in patients with PD and discuss the pathophysiological similarities and differences in the effects of DBS in comparison to dopaminergic medication. Targeted, selective modulation of brain networks by DBS and pharmacodynamic effects of L-DOPA therapy on the central nervous system are presented. Moreover, we outline the perioperative algorithms for PD patients before and directly after the implantation of DBS electrodes and strategies for the reduction of side effects and optimization of motor and non-motor symptoms

KI-gestützte Diagnostik der obstruktiven Schlafapnoe mittels delta – alpha Konnektivität am sensorimotorischen Cortex [Abstract]

Fragestellung: Die Modulation der delta-alpha Phasenamplituden-Kreuzfrequenzkopplung (PAKFK) kann die cerebro-corticale Informationsverarbeitung beeinflussen. Wir haben untersucht, ob diese frequenzband-spezifische Modulation bei Patienten mit obstruktiver Schlafapnoe (OSA) beeinträchtigt wird. Patienten und Methoden: Es wurden die C3- und C4- elektroencephalographischen Aufnahmen der Polysomnographien von 170 Teilnehmern (86 im Hauptdatensatz, 27 - 84 Jahre alt, 44 Teilnehmer mit Respiratorischen Disturbance Index RDI>15/h und 84 im Validierungsdatensatz, 35 - 75 Jahre alt, 42 davon mit RDI>15/h) ausgewertet. Der delta-alpha KFK-Modulationsindex (MI) wurde bei Patienten mit unterschiedlichem OSA-Schweregrad in den unterschiedlichen Schlafstadien am sensorimotorischen Cortex berechnet. Auch die Möglichkeit der Vorhersage des RDI mit Hilfe der Schlafstadien-spezifischen MIs unter Verwendung eines Support Vector Machine (SVM) - Algorithmus wurde getestet. Ergebnisse: In beiden Datensätzen wurde der delta-alpha KFK-MI an den kortikalen sensorimotorischen Bereichen bei Patienten mit RDI>15/h im Vergleich zu Patienten mit RDI≤15/h im Stadium NREM1 und REM signifikant (p15/h signifikant erhöht im Vergleich zu Patienten mit RDI≤15/h. Delta-alpha MI im REM-Stadium konnte mittels SVM zuverlässig (82% Genauigkeit) den RDI vorhersagen. Schlussfolgerungen: Diese Frequenzband- und Schlafstadien-spezifische sensorimotorische Diskonnektion unterstützt das Konzept einer kortikalen sensorimotorischen Dysfunktion bei OSA-Patienten. Zudem, bietet der delta-alpha MI im REM–Schlaf einen potenziellen objektiven neurophysiologischen Ersatzmarker der respiratorischen Störung bei OSA-Patienten an

Myelination- and immune-mediated MR-based brain network correlates

Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammatory and neurodegenerative processes. Despite demyelination being a hallmark of the disease, how it relates to neurodegeneration has still not been completely unraveled, and research is still ongoing into how these processes can be tracked non-invasively. Magnetic resonance imaging (MRI) derived brain network characteristics, which closely mirror disease processes and relate to functional impairment, recently became important variables for characterizing immune-mediated neurodegeneration; however, their histopathological basis remains unclear. Methods In order to determine the MRI-derived correlates of myelin dynamics and to test if brain network characteristics derived from diffusion tensor imaging reflect microstructural tissue reorganization, we took advantage of the cuprizone model of general demyelination in mice and performed longitudinal histological and imaging analyses with behavioral tests. By introducing cuprizone into the diet, we induced targeted and consistent demyelination of oligodendrocytes, over a period of 5 weeks. Subsequent myelin synthesis was enabled by reintroduction of normal food. Results Using specific immune-histological markers, we demonstrated that 2 weeks of cuprizone diet induced a 52% reduction of myelin content in the corpus callosum (CC) and a 35% reduction in the neocortex. An extended cuprizone diet increased myelin loss in the CC, while remyelination commenced in the neocortex. These histologically determined dynamics were reflected by MRI measurements from diffusion tensor imaging. Demyelination was associated with decreased fractional anisotropy (FA) values and increased modularity and clustering at the network level. MRI-derived modularization of the brain network and FA reduction in key anatomical regions, including the hippocampus, thalamus, and analyzed cortical areas, were closely related to impaired memory function and anxiety-like behavior. Conclusion Network-specific remyelination, shown by histology and MRI metrics, determined amelioration of functional performance and neuropsychiatric symptoms. Taken together, we illustrate the histological basis for the MRI-driven network responses to demyelination, where increased modularity leads to evolving damage and abnormal behavior in MS. Quantitative information about in vivo myelination processes is mirrored by diffusion-based imaging of microstructural integrity and network characteristics

Longitudinal cortical network reorganization in early relapsing-remitting multiple sclerosis

BACKGROUND: Network science provides powerful access to essential organizational principles of the brain. The aim of this study was to investigate longitudinal evolution of gray matter networks in early relapsing-remitting MS (RRMS) compared with healthy controls (HCs) and contrast network dynamics with conventional atrophy measurements. METHODS: For our longitudinal study, we investigated structural cortical networks over 1 year derived from 3T MRI in 203 individuals (92 early RRMS patients with mean disease duration of 12.1 ± 14.5 months and 101 HCs). Brain networks were computed based on cortical thickness inter-regional correlations and fed into graph theoretical analysis. Network connectivity measures (modularity, clustering coefficient, local efficiency, and transitivity) were compared between patients and HCs, and between patients with and without disease activity. Moreover, we calculated longitudinal brain volume changes and cortical atrophy patterns. RESULTS: Our analyses revealed strengthening of local network properties shown by increased modularity, clustering coefficient, local efficiency, and transitivity over time. These network dynamics were not detectable in the cortex of HCs over the same period and occurred independently of patients&#039; disease activity. Most notably, the described network reorganization was evident beyond detectable atrophy as characterized by conventional morphometric methods. CONCLUSION: In conclusion, our findings provide evidence for gray matter network reorganization subsequent to clinical disease manifestation in patients with early RRMS. An adaptive cortical response with increased local network characteristics favoring network segregation could play a primordial role for maintaining brain function in response to neuroinflammation

Sensorimotor Cortical Activity during Respiratory Arousals in Obstructive Sleep Apnea

Intensity of respiratory cortical arousals (RCA) is a pathophysiologic trait in obstructive sleep apnea (OSA) patients. We investigated the brain oscillatory features related to respiratory arousals in moderate and severe OSA. Raw electroencephalography (EEG) data recorded during polysomnography (PSG) of 102 OSA patients (32 females, mean age 51.6 ± 12 years) were retrospectively analyzed. Among all patients, 47 had moderate (respiratory distress index, RDI = 15–30/h) and 55 had severe (RDI > 30/h) OSA. Twenty RCA per sleep stage in each patient were randomly selected and a total of 10131 RCAs were analyzed. EEG signals obtained during, five seconds before and after the occurrence of each arousal were analyzed. The entropy (approximate (ApEn) and spectral (SpEn)) during each sleep stage (N1, N2 and REM) and area under the curve (AUC) of the EEG signal during the RCA was computed. Severe OSA compared to moderate OSA patients showed a significant decrease (p < 0.0001) in the AUC of the EEG signal during the RCA. Similarly, a significant decrease in spectral entropy, both before and after the RCA was observed, was observed in severe OSA patients when compared to moderate OSA patients. Contrarily, the approximate entropy showed an inverse pattern. The highest increase in approximate entropy was found in sleep stage N1. In conclusion, the dynamic range of sensorimotor cortical activity during respiratory arousals is sleep-stage specific, dependent on the frequency of respiratory events and uncoupled from autonomic activation. These findings could be useful for differential diagnosis of severe OSA from moderate OSA

Cross-frequency coupling between gamma oscillations and deep brain stimulation frequency in Parkinson's disease.

The disruption of pathologically enhanced beta oscillations is considered one of the key mechanisms mediating the clinical effects of deep brain stimulation on motor symptoms in Parkinson's disease. However, a specific modulation of other distinct physiological or pathological oscillatory activities could also play an important role in symptom control and motor function recovery during deep brain stimulation. Finely tuned gamma oscillations have been suggested to be prokinetic in nature, facilitating the preferential processing of physiological neural activity. In this study, we postulate that clinically effective high-frequency stimulation of the subthalamic nucleus imposes cross-frequency interactions with gamma oscillations in a cortico-subcortical network of interconnected regions and normalizes the balance between beta and gamma oscillations. To this end we acquired resting state high-density (256 channels) EEG from 31 patients with Parkinson's disease who underwent deep brain stimulation to compare spectral power and power-to-power cross-frequency coupling using a beamformer algorithm for coherent sources. To show that modulations exclusively relate to stimulation frequencies that alleviate motor symptoms, two clinically ineffective frequencies were tested as control conditions. We observed a robust reduction of beta and increase of gamma power, attested in the regions of a cortical (motor cortex, supplementary motor area, premotor cortex) and subcortical network (subthalamic nucleus and cerebellum). Additionally, we found a clear cross-frequency coupling of narrowband gamma frequencies to the stimulation frequency in all of these nodes, which negatively correlated with motor impairment. No such dynamics were revealed within the control posterior parietal cortex region. Furthermore, deep brain stimulation at clinically ineffective frequencies did not alter the source power spectra or cross-frequency coupling in any region. These findings demonstrate that clinically effective deep brain stimulation of the subthalamic nucleus differentially modifies different oscillatory activities in a widespread network of cortical and subcortical regions. Particularly the cross-frequency interactions between finely tuned gamma oscillations and the stimulation frequency may suggest an entrainment mechanism that could promote dynamic neural processing underlying motor symptom alleviation

Audiovisual integration in children with cochlear implants revealed through EEG and fNIRS

Sensory deprivation can offset the balance of audio versus visual information in multimodal processing. Such a phenomenon could persist for children born deaf, even after they receive cochlear implants (CIs), and could potentially explain why one modality is given priority over the other. Here, we recorded cortical responses to a single speaker uttering two syllables, presented in audio-only (A), visual-only (V), and audio-visual (AV) modes. Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) were successively recorded in seventy-five school-aged children. Twenty-five were children with normal hearing (NH) and fifty wore CIs, among whom 26 had relatively high language abilities (HL) comparable to those of NH children, while 24 others had low language abilities (LL). In EEG data, visual-evoked potentials were captured in occipital regions, in response to V and AV stimuli, and they were accentuated in the HL group compared to the LL group (the NH group being intermediate). Close to the vertex, auditory-evoked potentials were captured in response to A and AV stimuli and reflected a differential treatment of the two syllables but only in the NH group. None of the EEG metrics revealed any interaction between group and modality. In fNIRS data, each modality induced a corresponding activity in visual or auditory regions, but no group difference was observed in A, V, or AV stimulation. The present study did not reveal any sign of abnormal AV integration in children with CI. An efficient multimodal integrative network (at least for rudimentary speech materials) is clearly not a sufficient condition to exhibit good language and literacy