Right Hemisphere Lateralization in Neural Connectivity Within Fronto-Parietal Networks in Non-human Primates During a Visual Reaching Task

A fronto-parietal network, comprised of the posterior parietal cortex (PPC) and the dorsal premotor cortex (PMd) has been proposed to be involved in planning and guiding movement. However, the issue of how the network is expressed across the bilateral cortical area according to the effector's side remains unclear. In this study, we tested these questions using electrocorticographic (ECoG) recordings in non-human primates and using a simple visual guided reaching task that induced a left or right hand response based on relevant cues provided for the task. The findings indicate that right hemisphere lateralized network patterns in which the right PMd was strongly coordinated with bilateral PPC immediately after presentation of the movement cue occurred, while the coherence with the left PMd was not enhanced. No difference was found in the coherence pattern between the effector's side (left hand or right hand), but the strength of coherence was different, in that animals showed a higher coherence in the right hand response compared to the left. Our data support that right lateralization in long-range phase synchrony in the 10–20 Hz low beta band is involved in motor preparation stage, irrespective of the upcoming effector's side

Oscillatory signatures of unimodal, bimodal, and cross-modal sensory working memory

Neural oscillatory activity is an essential brain mechanism that enables and subserves a vast range of cognitive functions. Studying them non-invasively through electroencephalography (EEG) has proven to be an effective method of discovering associations between oscillations in different frequency bands and various cognitive functions. Studying the oscillatory dynamics of human working memory (WM) \u2013 a core component of human higher cognitive functioning \u2013 has been particularly fruitful, leading to insights about the mental processes, frequency bands, and brain areas involved. In addition to frequency band specificity, the application of source reconstruction methods has led to further insights by revealing specific brain areas associated with WM related processing. In the present study, we focused on the oscillatory power dynamics during sensory working memory (SWM) in auditory and tactile modalities in the alpha band. In a delayed comparison two alternative forced choice task participants received two seque ntial stimuli and had to respond whether the intensity of the second stimulus was stronger than that of the first stimulus. In three related EEG experiments we examined SWM processing under unimodal (stimulation in one modality), bimodal (stimulation in both modalities simultaneously), and cross -modal (sequential stimulation of the modalities) conditions. An additional non -WM control condition allowed us to explore not only the differences between auditory and tactile WM, but also the effects of the WM task itself on the delay period oscillatory activity within each sensory modality. Our results showed that, while the bimodal stimulation condition led to behavioral enhancement, an increased stimulus difference was necessary to maintain the same level of performance also in the cross-modal conditions. Localizing the oscillatory activity in the alpha band (8 \u2013 12Hz) revealed a clear disinhibitory effect over the somatosensory cortex during the early and the late delay period, while the mid-delay did not show any differences in SWM between the two modalities. A similar, albeit weaker , effect was observed over the auditory cortices. A right parietal reduction of alpha power emerged during the late delay when a tactile stimulus had to be compared cross-modally. This suggests the involvement of parietal somatosensory association cortex in the cross-modal transformation of the tactile stimulus. Lastly, the differences between cortical source distributions when contrasting unimodal and cross-modal conditions demonstrated that late delay effects do not reflect only anticipatory effects due to the upcoming modality, but also reflect the influence of the stimulus modality kept in WM. Contrasting the bimodal condition with the unimodal ones revealed a parametric beta band effect in a right parietal area during the early delay only in the bimodal condition, which suggests that beta oscillations might play a role in multimodal integration under SWM conditions. A second effect during the early delay period was observed in the theta (4 \u2013 7Hz) band. An early effect appeared when contrasting conditions in which the first stimuli were identical while the second stimuli differed across the conditions. This result suggests that the early delay period is already shaped by the anticipated comparison context. The clearest differences in the contrast between WM and non-WM task were observed in theta and gamma bands. Source localizing the condition differences suggested the involvement of hippocampal and fronto-central areas in carrying out the WM task. Furthermore, sensory cortices of the respective modality conditions showed the highest levels of connectivity with the rest of the brain during the late delay, further highlighting the involvement of gamma band oscillations in SWM related processing. Overall, this study demonstrates that the results obtained when studying SWM related processing strongly depend on the sensory modality examined and the type of WM task employed. Any observations with regard to SWM related oscillatory power dynamics should be explored in multiple contexts before drawing any generalized conclusions

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

Lower Beta: A Central Coordinator of Temporal Prediction in Multimodal Speech

How the brain decomposes and integrates information in multimodal speech perception is linked to oscillatory dynamics. However, how speech takes advantage of redundancy between different sensory modalities, and how this translates into specific oscillatory patterns remains unclear. We address the role of lower beta activity (~20 Hz), generally associated with motor functions, as an amodal central coordinator that receives bottom-up delta-theta copies from specific sensory areas and generate top-down temporal predictions for auditory entrainment. Dissociating temporal prediction from entrainment may explain how and why visual input benefits speech processing rather than adding cognitive load in multimodal speech perception. On the one hand, body movements convey prosodic and syllabic features at delta and theta rates (i.e., 1–3 Hz and 4–7 Hz). On the other hand, the natural precedence of visual input before auditory onsets may prepare the brain to anticipate and facilitate the integration of auditory delta-theta copies of the prosodic-syllabic structure. Here, we identify three fundamental criteria based on recent evidence and hypotheses, which support the notion that lower motor beta frequency may play a central and generic role in temporal prediction during speech perception. First, beta activity must respond to rhythmic stimulation across modalities. Second, beta power must respond to biological motion and speech-related movements conveying temporal information in multimodal speech processing. Third, temporal prediction may recruit a communication loop between motor and primary auditory cortices (PACs) via delta-to-beta cross-frequency coupling. We discuss evidence related to each criterion and extend these concepts to a beta-motivated framework of multimodal speech processing

Brain connectivity studied by fMRI: homologous network organization in the rat, monkey, and human

The mammalian brain is composed of functional networks operating at different spatial and temporal scales — characterized by patterns of interconnections linking sensory, motor, and cognitive systems. Assessment of brain connectivity has revealed that the structure and dynamics of large-scale network organization are altered in multiple disease states suggesting their use as diagnostic or prognostic indicators. Further investigation into the underlying mechanisms, organization, and alteration of large-scale brain networks requires homologous animal models that would allow neurophysiological recordings and experimental manipulations. My current dissertation presents a comprehensive assessment and comparison of rat, macaque, and human brain networks based on evaluation of intrinsic low-frequency fluctuations of the blood oxygen-level-dependent (BOLD) fMRI signal. The signal fluctuations, recorded in the absence of any task paradigm, have been shown to reflect anatomical connectivity and are presumed to be a hemodynamic manifestation of slow fluctuations in neuronal activity. Importantly, the technique circumvents many practical limitations of other methodologies and can be compared directly between multiple species. Networks of all species were found underlying multiple levels of sensory, motor, and cognitive processing. Remarkable homologous functional connectivity was found across all species, however network complexity was dramatically increased in primate compared to rodent species. Spontaneous temporal dynamics of the resting-state networks were also preserved across species. The results demonstrate that rats and macaques share remarkable homologous network organization with humans, thereby providing strong support for their use as an animal model in the study of normal and abnormal brain connectivity as well as aiding the interpretation of electrophysiological recordings within the context of large-scale brain networks

Discriminant Brain Connectivity Patterns of Performance Monitoring at Average and Single-Trial Levels

Electrophysiological and neuroimaging evidence suggest the existence of common mechanisms for monitoring erroneous events, independent of the source of errors. Previous works have described modulations of theta activity in the medial frontal cortex elicited by either self-generated errors or erroneous feedback. In turn, similar patterns have recently been reported to appear after the observation of external errors. We report cross-regional interactions after observation of errors at both average and single-trial levels. We recorded scalp electroencephalography (EEG) signals from 15 subjects while monitoring the movement of a cursor on a computer screen. Connectivity patterns, estimated using multivariate auto-regressive models, show increased error-related modulations of the information transfer in the theta and alpha bands between frontocentral and frontolateral areas. Conversely, a decrease of connectivity in the beta band is also observed. These network patterns are similar to those elicited by self-generated errors. However, since no motor response is required, they appear to be related to intrinsic mechanisms of error processing, instead of being linked to co-activation of motor areas. Noticeably, we demonstrate that cross-regional interaction patterns can be estimated on a trial-by-trial basis. These trial-specific patterns, consistent with the multi-trial analysis, convey discriminant information on whether a trial was elicited by observation of an erroneous action. Overall, our study supports the role of frequency-specific modulations in the medial frontal cortex in coordinating cross-regional activity during cognitive monitoring at a single-trial basis

Neuronal nicotinic receptors as targets for enhancing cognition in schizophrenia

PhD ThesisCognitive deficits are a core disabling feature of schizophrenia, yet remain inadequately treated by current pharmacological or behavioural therapies. The non-competitive NMDAR antagonist ketamine can pharmacologically induce cognitive deficits in both rodents and humans, presenting a novel translational approach for examining mechanisms underlying cognitive deficits associated with schizophrenia (CDS). Nicotine can improve working memory in rodents and in smokers with schizophrenia where heavy tobacco use may reflect self-medication to ameliorate CDS. The roles of the two main subtypes of nAChRs, the α7 and α4β2, in mediating cognitive improvement have yet to be determined. Cohorts of male hooded-Lister rats were trained in the Odour Span Task (OST) until demonstrating asymptotic performance and then exposed to a sub-anaesthetic dose of ketamine or vehicle daily for 5 consecutive days. This sub-chronic regimen produced a replicable, dose-dependent impairment in OST performance that was not restored following anti-psychotic treatment. Nicotine, α7 and α4β2 nAChR-selective agonists improved performance in ketamine-treated animals, with nicotine and one α4β2 agonist also improving the performance of control subjects. These data indicate the α4β2 nAChR as the main receptor subtype mediating the effect of nicotine on the OST in control animals, with a lesser role for the α7 nAChR. The α7 nAChR however was shown to have a role in improving the performance of ketamine-treated animals, as demonstrated by the enhancing effect of allosteric modulator PNU-120596 and Compound T on OST performance; an effect that was blocked by the α7 nAChR antagonist methyllycaconitine. When administered locally into the medial prefrontal cortex (mPFC), nicotine improved, and muscimol impaired OST performance; suggesting the mPFC as the neural site of action in the OST. Complementary data using an in-vitro electrophysiological gamma frequency model of network oscillations indicated an enhancing effect of nicotine on normal gamma frequency oscillations in the rat mPFC and is proposed as a potential mechanism behind the behavioural data. Collectively, these results provide further impetus for targeting nAChRs in the treatment of CDS

The role of oscillatory synchrony in motor control.

Synchronized oscillations are manifest in various regions in the motor system. Their variable nature has increased the interest in the functional significance. Subcortical and cortical activity in the beta band is pathologically increased in Parkinson's disease (PD) - a state dominated by bradykinesia and rigidity. After the administration of the drug levodopa, beta activity and motor impairment are substantially decreased, while activity in the gamma band is increased. The function of beta bursts within the healthy motor system remains unknown. Recent evidence suggests that beta activity may promote the existing motor set and posture. In this thesis, with the use of positional hold tasks the role of beta activity on performance will be examined. It will be demonstrated that during bursts of beta synchrony in the corticomuscular system of healthy subjects there is an improvement, in the performance of these tasks. The findings will argue that physiological fluctuations in the beta band in the motor system may be of behavioural advantage during fine postural tasks involving the hand. The present work will also examine the role of population oscillations in the parkinsonian basal ganglia. It will demonstrate that under levodopa treatment the pattern of movement-related reactivity in the subthalamic nucleus (STN) and the pedunculopontine nucleus (PPN) as well as the background activity in the PPN change significantly. It will be shown that levodopa suppresses movement-related beta activity around the time of self-paced movements and promotes the increase of movement-related gamma activity contralateral to the movement side, following the same pattern as in the non dopamine-depleted brain. This suggests that dopaminergic therapy restores a more physiological pattern of reactivity in the STN. In the untreated state, beta activity in the STN will be shown to be modulated during repetitive self-paced movements, reflecting a role in ongoing performance, but only when motor performance is maximal and not when bradykinesia occurs. Finally, it will be demonstrated that levodopa promotes alpha band activity in the PPN at rest and before movement suggesting a possible physiological role of this activity in this nucleus. These observations provide further insight in the function of neuronal synchronization in the motor system in health and disease