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Motor response selection is the process by which an intention to act is transformed into an action; this multifaceted process occurs at the interface between cognitive and motor systems. Despite the importance of response selection, the nature and neural implementation of this process is still a subject of debate (Thompson-Schill et al, 1997; Botvinick et al., 2001; Rushworth et al., 2004; Nachev et al., 2007). While previous research has demonstrated that the selection of finger movements relies on a distributed network involving premotor and prefrontal areas, the specific contribution of these regions, however, remains unclear. It is also unclear if the selection of words engages similar processes as the selection of finger movements, that is, if response selection is a domain-general or a domain-specific process. In order to address these issues, a set of four complementary studies using functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) was developed in which different factors affecting response selection were examined: selection mode, response type (words vs. oral movements), attention and response competition (conflict). / The results of these studies provide new insights into the neural architecture of response selection by uncovering the respective contribution of premotor areas (pre-SMA and PMA) and prefrontal areas (DLPFC and IFG). A preliminary two-stage model of response selection is proposed, in which the PMA is generating a set of response alternatives from which the pre-SMA performs selection using one of two different mechanisms (response facilitation and response inhibition). In general, these findings do not support the hypothesis of a medio-lateral gradient of control (Goldberg, 1985) but confirm the fundamental role of the lateral (PMA) and medial (pre-SMA) premotor areas in the process of selecting motor responses. / Importantly, the results also demonstrate that selection is a domain-general (response-independent) process. Uncovering the general, multifaceted nature of brain mechanisms is essential to reveal the basic units of control in the central nervous system; this knowledge is fundamental to broaden current understanding of the basic brain operations that are used to produce language. Theoretical and clinical implications of these findings are discussed.

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.

Swallowing impairment or dysphagia can be a consequence of several neurological and anatomical disorders such as stroke, Parkinson’s diseases, and head and neck cancer. Management of patients with dysphagia often involves diet modification, sensory stimulation, and exercise programme with the primary goal being safe swallowing to maintain nutrition. The aim of this project was to evaluate the effects of lemon odour and tastant on swallowing behaviour in healthy young adults. Specifically, the neural excitability and biomechanical characteristics of swallowing were measured in two studies. Neural excitability was evaluated by measuring motor-evoked potentials (MEPs) from the submental muscles which were evoked by transcranial magnetic stimulation (TMS) of the motor cortex. Biomechanical characteristics were evaluated through measures of submental muscle contraction, pressure changes in the oral cavity and pharynx, and the dynamics of the upper oesophageal sphincter (UES). Two groups of volunteers (16 in each group) participated in two separate studies. In the MEP study, 25% and 100% concentrations of lemon concentrate were presented separately as olfactory and gustatory stimuli. The four stimuli were randomly presented in four separate sessions. The olfactory stimulus was nebulized and presented via nasal cannula. Filter paper strips impregnated with the lemon concentrate placed on the tongue served as the gustatory stimulus. Tap water was used as control. TMS-evoked MEPs were measured at baseline, during control condition, during stimulation, immediately poststimulation, and at 30-, 60-, and 90-min poststimulation. Experiments were repeated using the combination of odour and tastant concentration that most significantly influenced the MEP. The biomechanical study used (a) surface electromyography (sEMG) to record contraction of the submental muscles, (b) lingual array with pressure transducers to record glossopalatal pressures, and (c) pharyngeal manometry to record pressures in the pharynx and the UES. Similar methods of presenting the stimuli were used to randomly present the 25% and 100% concentrations of lemon odour and tastant. All data were recorded concurrently during stimulation. The concentration of odour and tastant that produced the largest submental sEMG amplitude was selected for presentation of combined stimulation. Data were then recorded during combined stimulation and at 30-, 60-, and 90-min poststimulation. Results from the MEP study showed increased MEP amplitude at 30-, 60-, and 90-min poststimulation during swallowing compared to baseline, but only for the combined stimulation. Poststimulation results from the biomechanical study showed decreased middle glossopalatal pressure at 30 min and decreased anterior and middle glossopalatal contact duration at 60 min. No poststimulation changes were found in sEMG and pharyngeal manometry measures. During combined odour and tastant stimulation, there were increased pressure and contact duration at the anterior glossopalatal contact and decreased hypopharyngeal pressure. Generally, these changes correspond to increased efficiency of swallowing. In conclusion, these are the first studies to have measured the effects of flavour on neural excitability and biomechanics of swallowing and the first to have shown changes in MEP and several biomechanical characteristics of swallowing following flavour stimulation. These changes were present poststimulation, suggesting mechanisms of neural plasticity that may underlie potential value in the rehabilitation of patients with dysphagia.

Transkranijinė magnetinė stimuliacija (TMS) – tai modernus neinvazinis vaistams rezistentiškų psichiatrinių sutrikimų gydymo būdas. Fiziologiniai TMS tyrimai pasižymi įvairiais, dažnai prieštaringais rezultatais, daugeliu atvejų didžiausias dėmesys skiriamas betarpiškiems poveikiams po vienos TMS procedūros, bet ne po pilno terapinio kurso. Manoma, kad rezultatų įvairovę TMS praktikoje įtakoja skirtingi stimuliacijos parametrai ir netikslumai parenkant stimuliuojamą zoną smegenyse. Nors TMS terapija dažnai traktuojama kaip švelnesnė alternatyva elektros impulsų terapijai (EIT), palyginamųjų fiziologinių šių metodikų tyrimų labai trūksta. Darbo tikslas buvo įvertinti TMS terapijos kurso poveikį bioelektriniam galvos smegenų aktyvumui ir palyginti jį su EIT terapijos poveikiu. Buvo tirta aukšto ir žemo dažnių (10 Hz ir 1 Hz) TMS terapijos įtaka EEG dažnių galios spektrui bei sukeltiniam klausos potencialui P300, naudojant standartinį ir neuronavigacinį taikinio pozicionavimą. TMS sukelti EEG pokyčiai palyginti su EIT terapijos sukeltais EEG pokyčiais, išmatuota TMS terapijos sąlygotų pokyčių dinamika kelių mėnesių bėgyje. Rezultatai parodė, kad TMS terapijos pasekoje smegenyse ryškiausiai padidėja delta dažnio galia. Naudojant standartinį pozicionavimą 10 Hz TMS sukėlė įvairesnius ir intensyvesnius EEG galios spektro pokyčius nei 1 Hz TMS. Pritaikius neuronavigacinę sistemą 10 Hz TMS atveju sumažėjo teta ir alfa dažnių galios pokyčiai. Praėjus keliems mėnesiams nuo TMS... [toliau žr. visą tekstą] / Transcranial magnetic stimulation (TMS) is a modern non invasive method of drug resistant psychiatric disorder treatment. TMS physiology research is hindered by variable, often controversial results. In most studies main attention is being focused on immediate effects after single TMS procedure rather than the influence of a complete therapy course. It is considered that variability of results in TMS practice is caused by different stimulation parameters and imprecision of stimulated area placement in the brain. Although TMS therapy is often viewed as a milder alternative to electroconvulsive therapy (ECT), comparative physiological studies of these two methods are very rare. The aim of this study was to evaluate the effect of rTMS therapy course on bioelectrical brain activity and compare it to an ECT effect. Research included the effect of high and low frequency (10 Hz and 1 Hz) TMS on EEG band power spectrum and auditory evoked potential P300, using both standard and neuronavigated target positioning. TMS evoked EEG changes were also compared to the changes of ECT. Change dynamics after several months of TMS therapy were also measured. Results showed that after TMS therapy the most notable change in the brain occurs in the form of delta power increase. When using standard positioning 10 Hz TMS evokes more diverse and intense EEG band power spectrum changes than the 1 Hz TMS. Application of neuronavigation system decreases theta and alpha band power changes in 10 Hz TMS... [to full text]

Transcranial magnetic stimulation (TMS) is a modern non invasive method of drug resistant psychiatric disorder treatment. TMS physiology research is hindered by variable, often controversial results. In most studies main attention is being focused on immediate effects after single TMS procedure rather than the influence of a complete therapy course. It is considered that variability of results in TMS practice is caused by different stimulation parameters and imprecision of stimulated area placement in the brain. Although TMS therapy is often viewed as a milder alternative to electroconvulsive therapy (ECT), comparative physiological studies of these two methods are very rare. The aim of this study was to evaluate the effect of rTMS therapy course on bioelectrical brain activity and compare it to an ECT effect. Research included the effect of high and low frequency (10 Hz and 1 Hz) TMS on EEG band power spectrum and auditory evoked potential P300, using both standard and neuronavigated target positioning. TMS evoked EEG changes were also compared to the changes of ECT. Change dynamics after several months of TMS therapy were also measured. Results showed that after TMS therapy the most notable change in the brain occurs in the form of delta power increase. When using standard positioning 10 Hz TMS evokes more diverse and intense EEG band power spectrum changes than the 1 Hz TMS. Application of neuronavigation system decreases theta and alpha band power changes in 10 Hz TMS... [to full text] / Transkranijinė magnetinė stimuliacija (TMS) – tai modernus neinvazinis vaistams rezistentiškų psichiatrinių sutrikimų gydymo būdas. Fiziologiniai TMS tyrimai pasižymi įvairiais, dažnai prieštaringais rezultatais, daugeliu atvejų didžiausias dėmesys skiriamas betarpiškiems poveikiams po vienos TMS procedūros, bet ne po pilno terapinio kurso. Manoma, kad rezultatų įvairovę TMS praktikoje įtakoja skirtingi stimuliacijos parametrai ir netikslumai parenkant stimuliuojamą zoną smegenyse. Nors TMS terapija dažnai traktuojama kaip švelnesnė alternatyva elektros impulsų terapijai (EIT), palyginamųjų fiziologinių šių metodikų tyrimų labai trūksta. Darbo tikslas buvo įvertinti TMS terapijos kurso poveikį bioelektriniam galvos smegenų aktyvumui ir palyginti jį su EIT terapijos poveikiu. Buvo tirta aukšto ir žemo dažnių (10 Hz ir 1 Hz) TMS terapijos įtaka EEG dažnių galios spektrui bei sukeltiniam klausos potencialui P300, naudojant standartinį ir neuronavigacinį taikinio pozicionavimą. TMS sukelti EEG pokyčiai palyginti su EIT terapijos sukeltais EEG pokyčiais, išmatuota TMS terapijos sąlygotų pokyčių dinamika kelių mėnesių bėgyje. Rezultatai parodė, kad TMS terapijos pasekoje smegenyse ryškiausiai padidėja delta dažnio galia. Naudojant standartinį pozicionavimą 10 Hz TMS sukėlė įvairesnius ir intensyvesnius EEG galios spektro pokyčius nei 1 Hz TMS. Pritaikius neuronavigacinę sistemą 10 Hz TMS atveju sumažėjo teta ir alfa dažnių galios pokyčiai. Praėjus keliems mėnesiams nuo TMS... [toliau žr. visą tekstą]

This thesis describes experiments designed to investigate the effects of neuromuscular electrical stimulation (NMES) on corticospinal (CS) excitability in humans. NMES delivered at 100 Hz was more effective for increasing CS excitability than 10-, 50-, or 200-Hz NMES. CS excitability increases occurred after 24 min of 100-Hz NMES, were strongest in the stimulated muscle, and were mediated primarily at a supraspinal level. NMES of the common peroneal nerve of the leg increased CS excitability in multiple leg muscles, whereas NMES of the median nerve of the hand increased CS excitability in only the muscle innervated by that nerve. Additionally, CS excitability for the hand increased after 40 min of relatively high intensity and frequency NMES but not after 2 h of lower intensity and frequency NMES. These results have implications for identifying optimal NMES parameters to augment CS excitability for rehabilitation after central nervous system injury.

The purpose of this thesis was to investigate the potential mechanisms and sites of neural adaptations that mediate cross-limb transfer of strength and motor learning that can occur subsequent to unilateral training. Better understanding of the mechanisms should allow therapeutic benefits of this effect to be assessed. There are two main classes of mechanisms that could contribute to cross-limb transfer. The first is described by the ??bilateral access?? hypothesis, which suggests that neural adaptations induced by training reside in bilaterally projecting motor areas that are accessible to the untrained (ipsilateral) hemisphere during task execution to facilitate performance. According to the alternative ??cross-activation?? hypothesis, activation of the untrained hemisphere during unilateral training leads to adaptations in the untrained hemisphere that cause improved performance with the opposite untrained limb. A series of studies were conducted in this research. We directly tested the cross-activation hypothesis via a reliable twitch interpolation technique involving transcranial magnetic stimulation (TMS). Four-weeks of strength training for the right wrist increased neural drive (from the untrained motor cortex) to the untrained left wrist. The data demonstrate that strength training of one limb can influence the efficacy of corticospinal pathways that project to the opposite untrained limb, consistent with the cross-activation hypothesis. To investigate the contribution of each hemisphere in cross-limb transfer, we applied repetitive TMS (rTMS) to the trained or the untrained motor cortex to disrupt brain processing after unilateral ballistic training. Learning to produce ballistic movements requires optimization of motor drive to the relevant muscles in a way that resembles high-force contractions performed during strength training. Ballistic skill transferred rapidly to the untrained hand and the improved performance was accompanied by bilateral increases in corticospinal excitability. Performance improvement in each hand was specifically suppressed by rTMS of the opposite hemisphere. Thus the motor cortex ipsilateral to the trained hand is critically altered during unilateral training; and neural adaptations within this untrained hemisphere are crucial in cross-limb transfer of ballistic skill. Overall, the data are in agreement with the cross-activation hypothesis for high-force and ballistic tasks, although they do not exclude the potential involvement of bilateral access mechanisms.

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.

The purpose of this thesis was to investigate the potential mechanisms and sites of neural adaptations that mediate cross-limb transfer of strength and motor learning that can occur subsequent to unilateral training. Better understanding of the mechanisms should allow therapeutic benefits of this effect to be assessed. There are two main classes of mechanisms that could contribute to cross-limb transfer. The first is described by the ??bilateral access?? hypothesis, which suggests that neural adaptations induced by training reside in bilaterally projecting motor areas that are accessible to the untrained (ipsilateral) hemisphere during task execution to facilitate performance. According to the alternative ??cross-activation?? hypothesis, activation of the untrained hemisphere during unilateral training leads to adaptations in the untrained hemisphere that cause improved performance with the opposite untrained limb. A series of studies were conducted in this research. We directly tested the cross-activation hypothesis via a reliable twitch interpolation technique involving transcranial magnetic stimulation (TMS). Four-weeks of strength training for the right wrist increased neural drive (from the untrained motor cortex) to the untrained left wrist. The data demonstrate that strength training of one limb can influence the efficacy of corticospinal pathways that project to the opposite untrained limb, consistent with the cross-activation hypothesis. To investigate the contribution of each hemisphere in cross-limb transfer, we applied repetitive TMS (rTMS) to the trained or the untrained motor cortex to disrupt brain processing after unilateral ballistic training. Learning to produce ballistic movements requires optimization of motor drive to the relevant muscles in a way that resembles high-force contractions performed during strength training. Ballistic skill transferred rapidly to the untrained hand and the improved performance was accompanied by bilateral increases in corticospinal excitability. Performance improvement in each hand was specifically suppressed by rTMS of the opposite hemisphere. Thus the motor cortex ipsilateral to the trained hand is critically altered during unilateral training; and neural adaptations within this untrained hemisphere are crucial in cross-limb transfer of ballistic skill. Overall, the data are in agreement with the cross-activation hypothesis for high-force and ballistic tasks, although they do not exclude the potential involvement of bilateral access mechanisms.