Neurobehavioral Strategies of Skill Acquisition in Left and Right Hand Dominant Individuals

The brain consists of vast networks of connected pathways communicating through synchronized electrochemical activity propagated along fiber tracts. The current understanding is that the brain has a modular organization where regions of specialized processes are dynamically coupled through long-range projections of dense axonal networks connecting spatially distinct regions enabling signal transfer necessary for all complex thought and behavior, including regulation of movement. The central objective of the dissertation was to understand how sensorimotor information is integrated, allowing for adaptable motor behavior and skill acquisition in the left-and right-hand dominant populations. To this end participants, of both left- and right-hand dominance, repeatedly completed a visually guided, force matching task while neurobiological and neurobehavioral outcome measurements were continuously recorded via EEG and EMG. Functional connectivity and graph theoretical measurements were derived from EEG. Cortico-cortical coherence patterns were used to infer neurostrategic discrepancies employed in the execution of a motor task for each population. EEG activity was also correlated with neuromuscular activity from EMG to calculate cortico-muscular connectivity. Neurological patterns and corresponding behavioral changes were used to express how hand dominance influenced the developing motor plan, thereby increasing understanding of the sensorimotor integration process. The cumulative findings indicated fundamental differences in how left- and right-hand dominant populations interact with the world. The right-hand dominant group was found to rely on visual information to inform motor behavior where the left-hand dominant group used visual information to update motor behavior. The left-hand group was found to have a more versatile motor plan, adaptable to both dominant, nondominant, and bimanual tasks. Compared to the right-hand group it might be said that they were more successful in encoding the task, however behaviorally they performed the same. The implications of the findings are relevant to both clinical and performance applications providing insight as to potential alternative methods of information integration. The inclusion of the left-hand dominant population in the growing conceptualization of the brain will generate a more complete, stable, and accurate understanding of our complex biology

Neurosystems: brain rhythms and cognitive processing

Neuronal rhythms are ubiquitous features of brain dynamics, and are highly correlated with cognitive processing. However, the relationship between the physiological mechanisms producing these rhythms and the functions associated with the rhythms remains mysterious. This article investigates the contributions of rhythms to basic cognitive computations (such as filtering signals by coherence and/or frequency) and to major cognitive functions (such as attention and multi-modal coordination). We offer support to the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations.098352 - Wellcome Trust; 5R01NS067199 - NINDS NIH HH

Neuromagnetic investigations of mechanisms and effects of STN-DBS and medication in Parkinson's disease

Parkinson’s disease (PD) is a neurodegenerative disorder cardinally marked by motor symptoms, but also sensory symptoms and several other non-motor symptoms. PD patients are typically treated with dopaminergic medication for several years. Many patients eventually experience bouts of periods where medication might not be able to effectively control symptoms as well as experience side-effects of long-term dopaminergic treatments. Deep brain stimulation (DBS) is an option as the next therapeutic recourse for such patients. DBS treatment essentially involves placement of stimulating electrodes in the subthalamic nucleus (STN) or the globus pallidus internum (GPi) along with an implanted pulse generator (IPG) in the sub-clavicular space. STN-DBS alleviates motor symptoms and leads to substantial improvements in quality of life for PD patients. Although DBS is known to improve several classes of symptoms, the effect mechanism of DBS is still not clear. While there is a lack of electrophysiological investigation of sensory processing and the effects of treatments in PD altogether, the electrophysiological studies of the cortical dynamics during motor tasks and at rest lack consensus.We recorded magnetoencephalography (MEG) and electromyography (EMG) from PD patients in three studies: (i) at rest, (ii) during median nerve stimulation, and (iii) while performing phasic contractions (hand gripping). The three studies focused on cortical oscillatory dynamics at rest, during somatosensory processing and during movement, respectively. The measurements were conducted in DBS-treated, untreated (DBS washout) and dopaminergic-medicated states. While both treatments (DBS and dopaminergic medication) ameliorated motor symptoms similarly in all studies, they showed differentiated effects on: (i) increased sensorimotor cortical low-gamma spectral power (31-45 Hz) (but no changes in beta power (13-30 Hz)) at rest only during DBS, (ii) somatosensory processing with higher gamma augmentation (31-45 Hz, 20-60 ms) in the dopaminergic-medicated state compared to DBS-treated and untreated states, and (iii) hand gripping with increased motor-related beta corticomuscular coherence (CMC, 13-30 Hz) during dopaminergic medication in contrast to increased gamma power (31-45 Hz) during DBS.Firstly, we infer from the three studies that DBS and dopaminergic medication employ partially different anatomo-functional pathways and functional strategies when improving PD symptoms. Secondly, we suggest that treatments act on pathological oscillatory dynamics differently at cortical and sub-cortical levels and may do so through more sophisticated mechanisms than mere suppression of the pathological spectral power in a particular band. And thirdly, we urge exploring effect mechanisms of PD treatments beyond the motor system. The effects of dopaminergic medication on early somatosensory processing has opened the door for exploring the effects of treatments and studying their mechanisms using electrophysiology, especially in higher order sensory deficits. Integration of such research findings into a holistic view on mechanisms of treatments could pave way for better disease management paradigms. 

TMS highlights the functional relevance and malleability of cortico-cortical connections to motion and action perception

In social environments the human brain evolves systems to make sense of others’ actions and behaviours, allowing the development of social interactions and reactions. Influential theories posit that the understanding of others’ actions is realised through the activation of one’s motor system that internally simulates the kinematics of the ongoing action and predicts its sensorial outcome. This process engages an action observation network (AON) that encompasses temporal-occipital visual and parietal-frontal motor regions. The flowing visual information is coupled with motor representations through recursive bidirectional fronto-temporal interactions that are modelled by sensorimotor experience allegedly via Hebbian plastic mechanisms. However, to date there is no direct evidence on the role that connectivity plays in carrying crucial information for the AON functioning. Recent studies demonstrated the efficacy of a TMS protocol, named cortico-cortical paired associative stimulation (ccPAS), able to induce transient Hebbian-like plastic potentiation in motor neural circuits. For a mechanistic understanding of AON connections relevance for simulative processes and action prediction, we used ccPAS with the aim of empowering the synaptic efficacy of the connections between the nodes of the system. ccPAS impact on behaviour and neurophysiological responses was evaluated. On motor behaviour, a ccPAS to empower premotor-motor connectivity led to improved dexterity (Study I) revealing the circuit’s functional malleability. On low-level perception, ccPAS, boosting the re-entrant connectivity of visual cortices revealed changes in motion perception and in specific features of it (Studies II-III). We then demonstrated that premotor-motor circuit conveys crucial information for the motor simulation of observed movements (Study IV), and finally, that empowering feedback connectivity in the AON enhances action prediction accuracy (Study V). We therefore provided evidence on the functional relevance of AON connectivity that supports theoretical models, and we developed an innovative tool able to promote AON functionality by inducing plastic changes in its connections

Nicht-invasive elektrophysiologische Biomarker des Alterns und der Parkinson-Krankheit

Parkinson’s disease (PD) is a frequent neurodegenerative disorder. It mainly affects motor functions and it has a long preclinical phase. Dopaminergic medication is an effective treatment but also comes with adverse effects. Therefore, investigating early biomarkers of PD and effects of dopaminergic medication is crucial for advancing the understanding and treatment of this disease. In my dissertation, two studies are presented that contribute to this field. In the first study, we studied PD-related neuronal biomarkers, including excessive PAC (phase-amplitude coupling) between the beta phase and amplitude from broadband gamma and abnormal beta burst dynamics in a group of young (N=71, age 20–35 years) and apparently healthy elderly (N=66, age 59–77 years) subjects with electroencephalography (EEG) recordings. In the second study, based on a group of patients with PD (N=15), we investigated the effects of dopaminergic medication on non-oscillatory component of the neural activity (estimated by the spectral slope), the inter-areal functional connectivity and functional network’s configuration properties. The results from the first study confirmed that the elderly subjects show elevated PAC compared to the younger ones; and this effect is most pronounced in motor-related areas. In addition, the elderly are characterized by prolonged and more often bursting beta activity compared to the young subjects. In the second study, we observed that the spectral slope is steeper after dopaminergic medication intake. Moreover, the medication administration induces an up-regulation of the inter-regional connectivity in the beta band, mainly in fronto-centro-parietal regions. However, there is no evidence showing a significant alteration in the global properties of the functional network. Interestingly, we found that only in the Off medication state there is a close association between the spectral slope and the integrative ability of the brain network. These effects are consistently present in the centro-parietal region. These findings provide evidence that the electrophysiological biomarkers associated with PD are also present in a group of presumably healthy elderly compared to a young one. This, in turn, indicates that these biomarkers might be promising for the detection of a pre-clinical stage of PD given a close relationship between aging and PD. Future prospective studies should test their unique predictive value in the development of PD. Furthermore, dopaminergic medication induces changes not only locally in the spectral slope but also in the interaction between the areas with a specific spatial interaction pattern. Crucially, the spectral slope (which may index the local excitation/inhibition ratio) appears to be essential in forming the global network’s ability to integrate information from remote areas in PD. This could be relevant for the interventional studies directed at non-invasive modulation of neuronal activity in these areas.Die Parkinson-Krankheit (PK) ist eine neurodegenerative Störung. Sie betrifft die motorischen Funktionen und hat eine lange präklinische Phase. Dopaminerge Medikamente (DM) sind eine wirksame Behandlung, haben aber auch Nebenwirkungen. Daher ist die Untersuchung früher Biomarker für PK und der Auswirkungen DM von Bedeutung, um das Verständnis und die Behandlung dieser Krankheit voranzutreiben. In meiner Dissertation werden zwei Studien vorgestellt, die einen Beitrag zu diesem Thema leisten. ​ In Studie 1 nutzten wir Elektroenzephalografie (EEG) und untersuchten neuronale PD-bezogene Biomarker, einschließlich erhöhter PAC (Phasen-Amplituden-Kopplung) zwischen der Beta-Phase und der Breitband-Gamma-Amplitude und abnormaler Beta-Burst-Dynamik in jungen (N=71, Alter 20-35 Jahre) und gesunden älteren (N=66, Alter 59–77 Jahre) Probanden. In Studie 2 mit PK-Patienten (N=15) untersuchten wir die Auswirkungen von DM auf die nicht-oszillatorische Komponente der neuronalen Aktivität, die interareale funktionelle Konnektivität und dessen Konfigurationseigenschaften. ​ Die Ergebnisse von Studie 1 bestätigten, dass ältere Probanden eine erhöhte PAC aufweisen; dieser Effekt ist in den motorischen Bereichen am stärksten ausgeprägt. Darüber hinaus weisen ältere Probanden eine verlängerte und häufiger auftretende Bursting-Beta-Aktivität auf. In Studie 2 beobachteten wir, dass die spektrale Steigung nach der DM-Einnahme steiler ist. Außerdem führt DM zu einer Hochregulierung der Konnektivität im Betaband, vor allem in fronto-zentral-parietalen Regionen. Es gibt jedoch keine Hinweise auf eine signifikante Veränderung der globalen Eigenschaften des funktionellen Netzwerks. Interessanterweise haben wir festgestellt, dass nur im Zustand „ohne“ DM ein enger Zusammenhang zwischen der spektralen Steigung und der Integrationsfähigkeit des Netzwerks besteht. Diese Effekte sind durchweg in der zentro-parietalen Region vorzufinden. ​ Diese Ergebnisse belegen, dass die EEG-Biomarker, die mit PK in Verbindung gebracht werden, auch in gesunden, älteren Menschen vorhanden sind. Dies wiederum deutet darauf hin, dass diese Biomarker vielversprechend für die Erkennung eines präklinischen Stadiums der PK sein könnten. Künftige prospektive Studien sollten ihren prädiktiven Wert in der Entwicklung der PK untersuchen. Darüber hinaus induzieren DM Veränderungen nicht nur lokal in der spektralen Steigung, sondern auch in der Interaktion zwischen den Bereichen mit einem bestimmten räumlichen Interaktionsmuster. Entscheidend ist, dass die spektrale Steigung (die möglicherweise das lokale Verhältnis zwischen Erregung und Hemmung anzeigt) für die Fähigkeit des globalen Netzwerks, Informationen aus entfernten Bereichen zu integrieren, bei der PK von Bedeutung ist. Dies könnte für interventionelle Studien relevant sein, die auf eine nicht-invasive Modulation der neuronalen Aktivität in diesen Bereichen abzielen