Neuromuscular electrical stimulation (NMES) has become an increasingly popular rehabilitative treatment approach for swallowing disorders (dysphagia). However, its precise effects on swallowing biomechanics and measures of swallowing neurophysiology are unclear. Clearly defined NMES treatment protocols that have been corroborated by thorough empirical research are lacking. The primary objective of this research programme was therefore to establish optimal NMES treatment parameters for the anterior hyo-mandibular (submental) musculature, a muscle group that is critically involved in the oral and pharyngeal phases of swallowing. Based on previous research, the primary hypothesis was that various NMES treatment protocols would have differential effects of either enhancing or inhibiting the excitability of corticobulbar projections to this muscle group. The research paradigm used to test this hypothesis was an evaluation of MEP amplitude and onset latency, recorded in the functional context of volitional contraction of the submental musculature (VC) and contraction of this muscle group during the pharyngeal phase of volitional swallowing (VPS, volitional pharyngeal swallow). Outcome measures were recorded before and at several time points after each NMES treatment trial. This methodology is similar to, but improved upon, research paradigms previously reported. Changes in corticobulbar excitability in response to various NMES treatment protocols were recorded in a series of experiments. Ten healthy research participants were recruited into a study that evaluated the effects of event-related NMES, whereas 15 healthy research participants were enrolled in a study that investigated the effects of non-event-related NMES. In a third cohort of 35 healthy research participants, task-dependent differences in corticobulbar excitability were evaluated during three conditions of submental muscle contraction: VC, VPS and submental muscle contraction during the pharyngeal phase of reflexive swallowing (RPS, reflexive pharyngeal swallowing). Event-related NMES induced frequency-depended changes in corticobulbar excitability. NMES administered at 80 Hz facilitated MEP amplitude, whereas NMES at 5 Hz and 20 Hz inhibited MEP amplitude. No changes were observed after NMES at 40 Hz. Maximal excitatory or inhibitory changes occurred 60 min post-treatment. Changes in MEP amplitude in response to event-related NMES were only observed when MEPs were recorded during the VC condition, whereas MEPs recorded during the VPS condition remained unaffected. Non-event-related NMES did not affect MEP amplitude in either of the muscle contraction conditions. Similarly, MEP onset latencies remained unchanged across all comparisons. MEPs were detected most consistently during the VC contraction condition. They were less frequently detected and were smaller in amplitude for the VPS condition and they were infrequently detected during pre-activation by RPS. The documented results indicate that event-related NMES has a more substantial impact on MEP amplitude than non-event-related NMES, producing excitatory and inhibitory effects. Comparison of MEPs recorded during VC, VPS and RPS suggests that different neural networks may govern the motor control of submental muscle activation during these tasks. This research programme is the first to investigate the effects of various NMES treatment protocols on the excitability of submental corticobulbar projections. It provides important new information for the use of NMES in clinical rehabilitation practices and our understanding of the neural networks governing swallowing motor control.

Neuromuscular electrical stimulation (NMES) has become an increasingly popular rehabilitative treatment approach for swallowing disorders (dysphagia). However, its precise effects on swallowing biomechanics and measures of swallowing neurophysiology are unclear. Clearly defined NMES treatment protocols that have been corroborated by thorough empirical research are lacking. The primary objective of this research programme was therefore to establish optimal NMES treatment parameters for the anterior hyo-mandibular (submental) musculature, a muscle group that is critically involved in the oral and pharyngeal phases of swallowing. Based on previous research, the primary hypothesis was that various NMES treatment protocols would have differential effects of either enhancing or inhibiting the excitability of corticobulbar projections to this muscle group. The research paradigm used to test this hypothesis was an evaluation of MEP amplitude and onset latency, recorded in the functional context of volitional contraction of the submental musculature (VC) and contraction of this muscle group during the pharyngeal phase of volitional swallowing (VPS, volitional pharyngeal swallow). Outcome measures were recorded before and at several time points after each NMES treatment trial. This methodology is similar to, but improved upon, research paradigms previously reported. Changes in corticobulbar excitability in response to various NMES treatment protocols were recorded in a series of experiments. Ten healthy research participants were recruited into a study that evaluated the effects of event-related NMES, whereas 15 healthy research participants were enrolled in a study that investigated the effects of non-event-related NMES. In a third cohort of 35 healthy research participants, task-dependent differences in corticobulbar excitability were evaluated during three conditions of submental muscle contraction: VC, VPS and submental muscle contraction during the pharyngeal phase of reflexive swallowing (RPS, reflexive pharyngeal swallowing). Event-related NMES induced frequency-depended changes in corticobulbar excitability. NMES administered at 80 Hz facilitated MEP amplitude, whereas NMES at 5 Hz and 20 Hz inhibited MEP amplitude. No changes were observed after NMES at 40 Hz. Maximal excitatory or inhibitory changes occurred 60 min post-treatment. Changes in MEP amplitude in response to event-related NMES were only observed when MEPs were recorded during the VC condition, whereas MEPs recorded during the VPS condition remained unaffected. Non-event-related NMES did not affect MEP amplitude in either of the muscle contraction conditions. Similarly, MEP onset latencies remained unchanged across all comparisons. MEPs were detected most consistently during the VC contraction condition. They were less frequently detected and were smaller in amplitude for the VPS condition and they were infrequently detected during pre-activation by RPS. The documented results indicate that event-related NMES has a more substantial impact on MEP amplitude than non-event-related NMES, producing excitatory and inhibitory effects. Comparison of MEPs recorded during VC, VPS and RPS suggests that different neural networks may govern the motor control of submental muscle activation during these tasks. This research programme is the first to investigate the effects of various NMES treatment protocols on the excitability of submental corticobulbar projections. It provides important new information for the use of NMES in clinical rehabilitation practices and our understanding of the neural networks governing swallowing motor control.

Die transkranielle Magnetstimulation (TMS) ist ein nichtinvasives Hirnstimulationsverfahren, mit welchem sowohl die funktionelle Untersuchung umschriebener kortikaler Regionen als auch die Modulation der Erregbarkeit ebendieser sowie die Induktion neuroplastischer Phänomene möglich ist. Sie wurde in der Vergangenheit insbesondere bei der Erforschung des humanen zentralmotorischen Systems angewandt. Dabei zeigte sich, dass ein einzelner über dem primärmotorischen Areal (M1) applizierter TMS-Puls multiple deszendierende Erregungswellen im Kortikospinaltrakt induzieren kann. Von diesen Undulationen besitzt die D-Welle (direkte Welle) die kürzeste Latenz und sie rekurriert auf eine direkte Aktivierung kortikospinaler Neurone, wohingegen I-Wellen (indirekte Wellen) längere Latenzen besitzen und durch transsynaptische Aktivierung dieser Zellen entstehen. Bemerkenswert ist das periodische Auftreten der letztgenannten Erregungswellen mit einer Periodendauer von etwa 1,5 ms. Zwar sind die genauen Mechanismen noch unbekannt, welche der Entstehung dieser I-Wellen sowie dem Phänomen der I-Wellen-Fazilitierung, das sich in geeigneten TMS-Doppelpulsprotokollen offenbart, zugrunde liegen, jedoch existieren hierzu verschiedene Erklärungsmodelle. Im Mittelpunkt der vorliegenden Arbeit steht die repetitive Anwendung eines TMS-Doppelpulsprotokolls, bei dem das Interpulsintervall (IPI) im Bereich der I-Wellen-Periodizität liegt (iTMS) und das gleichsam durch eine Implementierung der I-Wellen-Fazilitierung in der repetitiven TMS charakterisiert ist. Da gezeigt werden konnte, dass iTMS mit einem IPI von 1,5 ms (iTMS_1,5ms) die kortikospinale Erregbarkeit signifikant intra- und postinterventionell zu steigern vermag, und die I-Wellen-Periodizität interindividuellen Schwankungen unterliegt, wurde in der hier vorgestellten Studie an Normalprobanden der Einfluss einer individuellen Anpassung des IPIs (resultierend in der iTMS_adj) auf die intrainterventionelle kortikospinale Erregbarkeit untersucht. In der Tat stellte sich heraus, dass die iTMS_adj der iTMS_1,5ms diesbezüglich überlegen ist. Dieses Ergebnis unterstreicht das Potential einer Individualisierung der interventionellen TMS für erregbarkeitsmodulierende Effekte und macht dasjenige der ohnehin auf physiologische Prozesse abgestimmten iTMS explizit, was insbesondere für klinische Anwendungen relevant sein mag.

Die transkranielle Magnetstimulation (TMS) ist ein nichtinvasives Hirnstimulationsverfahren, mit welchem sowohl die funktionelle Untersuchung umschriebener kortikaler Regionen als auch die Modulation der Erregbarkeit ebendieser sowie die Induktion neuroplastischer Phänomene möglich ist. Sie wurde in der Vergangenheit insbesondere bei der Erforschung des humanen zentralmotorischen Systems angewandt. Dabei zeigte sich, dass ein einzelner über dem primärmotorischen Areal (M1) applizierter TMS-Puls multiple deszendierende Erregungswellen im Kortikospinaltrakt induzieren kann. Von diesen Undulationen besitzt die D-Welle (direkte Welle) die kürzeste Latenz und sie rekurriert auf eine direkte Aktivierung kortikospinaler Neurone, wohingegen I-Wellen (indirekte Wellen) längere Latenzen besitzen und durch transsynaptische Aktivierung dieser Zellen entstehen. Bemerkenswert ist das periodische Auftreten der letztgenannten Erregungswellen mit einer Periodendauer von etwa 1,5 ms. Zwar sind die genauen Mechanismen noch unbekannt, welche der Entstehung dieser I-Wellen sowie dem Phänomen der I-Wellen-Fazilitierung, das sich in geeigneten TMS-Doppelpulsprotokollen offenbart, zugrunde liegen, jedoch existieren hierzu verschiedene Erklärungsmodelle. Im Mittelpunkt der vorliegenden Arbeit steht die repetitive Anwendung eines TMS-Doppelpulsprotokolls, bei dem das Interpulsintervall (IPI) im Bereich der I-Wellen-Periodizität liegt (iTMS) und das gleichsam durch eine Implementierung der I-Wellen-Fazilitierung in der repetitiven TMS charakterisiert ist. Da gezeigt werden konnte, dass iTMS mit einem IPI von 1,5 ms (iTMS_1,5ms) die kortikospinale Erregbarkeit signifikant intra- und postinterventionell zu steigern vermag, und die I-Wellen-Periodizität interindividuellen Schwankungen unterliegt, wurde in der hier vorgestellten Studie an Normalprobanden der Einfluss einer individuellen Anpassung des IPIs (resultierend in der iTMS_adj) auf die intrainterventionelle kortikospinale Erregbarkeit untersucht. In der Tat stellte sich heraus, dass die iTMS_adj der iTMS_1,5ms diesbezüglich überlegen ist. Dieses Ergebnis unterstreicht das Potential einer Individualisierung der interventionellen TMS für erregbarkeitsmodulierende Effekte und macht dasjenige der ohnehin auf physiologische Prozesse abgestimmten iTMS explizit, was insbesondere für klinische Anwendungen relevant sein mag.

Epilepsy, as the most common chronic neurological disease, affects a significant part of population (0.5-1%). Drug resistant epilepsy has a significant negative effect on the quality of life, psychiatric comorbidities, neurocognitive performance and the risk of SUDEP in children. Therefore, resective epilepsy surgery, the only curative treatment of this condition, can fundamentally reverse this unfavorable prognosis. An inevitable prerequisite for a good postoperative result is complete removal of the epileptogenic zone (EC) and preservation of eloquent areas (EC). At present, even with improving and new preoperative non-invasive methods, we don't have an exclusive diagnostic method for theirs delineation. The aim of this PhD study is to assess benefit of individual intraoperative electrophysiological (iEF) methods in pediatric patients with focal intractable epilepsy. The first study evaluates the importance of intraoperative electrocorticography (iECoG) in the localization of EZ. The study proved that iECoG serves as a reliable tool to guide surgical resection and may predict results of epilepsy surgery. iECoG-based modification of surgical plan is not associated with increased risk of significant complications. The second presented study analyzed the contribution of intraoperative electrical...