Learning and adaptation in brain machine interfaces

Balancing subject learning and decoder adaptation is central to increasing brain machine interface (BMI) performance. We addressed these complementary aspects in two studies: (1) a learning study, in which mice modulated “beta” band activity to control a 1D auditory cursor, and (2) an adaptive decoding study, in which a simple recurrent artificial neural network (RNN) decoded intended saccade targets of monkeys. In the learning study, three mice successfully increased beta band power following trial initiations, and specifically increased beta burst durations from 157 ms to 182 ms, likely contributing to performance. Though the task did not explicitly require specific movements, all three mice appeared to modulate beta activity via active motor control and had consistent vibrissal motor cortex multiunit activity and local field potential relationships with contralateral whisker pad electromyograms. The increased burst durations may therefore by a direct result of increased motor activity. These findings suggest that only a subset of beta rhythm phenomenology can be volitionally modulated (e.g. the tonic “hold” beta), therefore limiting the possible set of successful beta neuromodulation strategies. In the adaptive decoding study, RNNs decoded delay period activity in oculomotor and working memory regions while monkeys performed a delayed saccade task. Adaptive decoding sessions began with brain-controlled trials using pre-trained RNN models, in contrast to static decoding sessions in which 300-500 initial eye-controlled training trials were performed. Closed loop RNN decoding performance was lower than predicted by offline simulations. More consistent delay period activity and saccade paths across trials were associated with higher decoding performance. Despite the advantage of consistency, one monkey’s delay period activity patterns changed over the first week of adaptive decoding, and the other monkey’s saccades were more erratic during adaptive decoding than during static decoding sessions. It is possible that the altered session paradigm eliminating eye-controlled training trials led to either frustration or exploratory learning, causing the neural and behavioral changes. Considering neural control and decoder adaptation of BMIs in these studies, future work should improve the “two-learner” subject-decoder system by better modeling the interaction between underlying brain states (and possibly their modulation) and the neural signatures representing desired outcomes

Rhythmic Action Synchronizes Memory Replay During Reinforcement Learning

Our cognitive abilities - learning from the past, sensing the current environment, planning into the future, executing an action, and infusing value into an experience - all rely on precisely timed and widespread electrical communications across neural networks. The brain’s hippocampal formation receives multimodal input, forges episodic associations, and predicts future state. Oscillating electrical bursts originating from the hippocampus, termed ‘sharp-wave ripples’ (SWR), often contain patterns of previously expressed neural spike sequences, and are necessary for certain forms of learning and memory. The discharge of SWR-replay resonates in remote parts of the brain and displays specific characteristics depending on a subject’s state of awareness and sensory context. In the sleep state, when motoric repertoire is limited, waves of breathing synchronize neural activity in several regions of the brain, including SWRs of the hippocampus. During active sensation of the awake state, cyclic licking dynamically entrains taste-reward networks in subcortical and cortical areas throughout learning. However, the neural correlates linking oromotor movements in the active learning state to the memory system of the hippocampal formation have not yet been established. Given the recurrence of SWR-replay during rhythmic ingestion of reinforcement learning and the hierarchical coupling of orofacial behaviors, we hypothesized that repeated licking could provide the oscillatory framework to synchronize memory reactivation during active learning. We approach this question with new technology development to track licking events at a reward port (P-event) during behavior on a spatial alternation task. Additionally, we developed a modular brain implant to simultaneously record from hippocampal area CA1 and medial entorhinal cortex (MEC) - interconnected brain regions that are crucial to episodic memory processing. Along with the co-modulation of individual neurons by licking and SWRs, we provide the first evidence that SWRs detected in dorsal CA1 synchronize with the phase of P-event cycle during learning. Furthermore, we confirmed that SWRs occurring during licking bouts contain neural reactivation of active navigation and trigger enhanced ripple-frequency power in downstream MEC. These results connect movement with memory and may assist in addressing abnormal ingestion behaviors that negatively affect mental or physical healt

Quasi-periodic patterns of brain intrinsic activity coordinate the functional connections in humans

The brain is a complex self-organizing biophysical system and intrinsically very active. How such intrinsic activity organizes the brain in humans is widely being studied during resting-state using functional magnetic resonance imaging (rsfMRI) and the functional connectivity (FC) metric. FC, calculated as the Pearson correlation between rsfMRI timeseries from different brain areas, indicates coherent activity on average over time, and can reflect some spatial aspects of the brain’s intrinsic organization. For example, based on the FC profile of each area, the cerebral cortex can be parcellated into a few resting-state networks (RSNs) or exhibit a few functional connectivity gradients (FCGs). Brain is a complex system and exhibits varied dynamic spatiotemporal regimes of coherent activity, which are still poorly understood. A subset of such regimes should be giving rise to FC, yet they might entail significantly insightful aspects about the brain’s self-organizing processes, which cannot be captured by FC. Among such dynamic regimes is the quasi-periodic pattern (QPP), obtained by identifying and averaging similar ~20s-long segments of rsfMRI timeseries. QPP involves a cycle of activation and deactivation of different areas with different timings, such that the overall activity within QPP resembles RSNs and FCGs, suggesting QPP might be contributing to FC. To robustly detect multiple QPPs, method improvements were implemented and three primary QPPs were thoroughly characterized. Within these QPPs activity propagates along the functional gradients at the cerebral cortex and most subcortical regions, in a well-coordinated way, because of the consistencies and synchronies across all brain regions which reasonably accord with the consensus on the structural connections. Nuanced timing differences between regions and the closed flow of activity throughout the brain suggest drivers for these patterns. When three QPPs are removed from rsfMRI timeseries, FC within and particularly between RSNs remarkably reduces, illustrating their dominant contribution. Together, our results suggest a few recurring spatiotemporal patterns of intrinsic activity might be dominantly coordinating the functional connections across the whole brain and serving self-organization. These intrinsic patterns possibly interact with the external tasks, affecting performance, or might provide more sensitive biomarkers in certain disorders and diseases.Ph.D

Advanced Invasive Neurophysiological Methods to Aid Decision Making in Paediatric Epilepsy Surgery

For patients with drug-resistant focal epilepsy, surgery is the most effective treatment to attain seizure freedom. Intracranial electroencephalogram investigations succeed in defining the seizure onset zone (SOZ) where non-invasive methods fail to identify a single seizure generator. However, resection of the SOZ does not always lead to a surgical benefit and, in addition, eloquent functions like language might be compromised. The aim of this thesis was to use advanced invasive neurophysiological methods to improve pre-surgical planning in two ways. The first aim was to improve delineation of the pathological tissue, the SOZ using novel quantitative neurophysiological biomarkers: high gamma activity (80–150Hz) phase-locked to low frequency iEEG discharges (phase-locked high gamma, PLHG) and high frequency oscillations called fast ripples (FR, 250–500Hz). Resection of contacts containing these markers were recently reported to lead to an improved seizure outcome. The current work shows the first replication of the PLHG metric in a small adult pilot study and a larger paediatric cohort. Furthermore, I tested whether surgical removal of PLHG- and/or FR-generating brain areas resulted in better outcome compared to the current clinical SOZ delineation. The second aim of this work was to aid delineation of eloquent language cortex. Invasive event-related potentials (iERP) and spectral changes in the beta and gamma frequency bands were used to determine cortical dynamics during speech perception and production across widespread brain regions. Furthermore, the relationship between these cortical dynamics and the relationship to electrical stimulation responses was explored. For delineation of pathological tissue, the combination of FRs and SOZ proved to be a promising biomarker. Localising language cortex showed the highest level of activity around the perisylvian brain regions with a significantly higher occurrence rate of iERPs compared to spectral changes. Concerning electrical stimulation mapping beta and high gamma frequency bands represented the most promising markers

Sleep, sleep-disordered-breathing : cognition and prematurity

Tese de doutoramento, Medicina (Psiquiatria e Saúde Mental), Universidade de Lisboa, Faculdade de Medicina, 2018Prematurity leads to many handicaps, some of them are only recognized later in life and may impact the individuals for the rest of their life. The delivery date compared to the full term delivery time will be a measure of “indication of risks” of post-natal handicap risk, but this is only one of the many measurements that can be looked at. Many studies have investigated development of premature infants, based on different criteria at entry in the considered study. Our investigations are only a limited contribution to the investigation of premature infants. We included infants born as young as 24 weeks of gestational-age [GA] but none of the infants had major neurological syndromes recognized at birth. “Normal infants” defined as infants with more than 37 weeks of GA, birth-weight >2500g and absence of any indication of health problems born in the same hospital maternity at same time as premature infants were also recruited to serve as normal controls. As most newborn infants spend a large amount of time asleep, all the presented studies include investigation of sleep, and once sleep-time occurred mostly during the nocturnal period, it focused on the polygraphic monitoring of the nocturnal sleep. The premature cohort study was a longitudinal study and parents who signed informed consent approved by the Chang Gung Hospital and Medical College Ethic Committee, were asked to come back on a yearly basis for at least 5 years. This is an on-going study and not every child has been followed for such time. Furthermore, as in any longitudinal study, loss of patients occurred as parents did not bring children back. At entry 400 parents signed the informed consent, currently at 5 years follow-up 150 children have ended the follow-up period and about 215 at 4 years. The sample is a non-random convenience sample of children selected based on the parents` willingness to participate in the protocol and obtained with the help of neonatologist physicians in our NICUs. Most of the studies presented in the thesis come-out of this longitudinal study. The studies asked specific questions, particularly looking at development of abnormal obstructive breathing during sleep. But some of our studies looked also at children of older age as some of the findings that we observed in our premature cohort needed a different investigative approach, and prior validation on older children-premature and in non-premature infants. We have included these studies in our narrative as they become part of our research, and they are part of a general research program on “sleep- breathing-and-cognition” in children

Topics in Cancer Survivorship

Cancer is now the leading cause of death in the world. In the U.S., one in two men and one in three women will be diagnosed with a non-skin cancer in their lifetime. Cancer patients are living longer than ever before. For instance, when detected early, the five-year survival for breast cancer is 98%, and it is about 84% in patients with regional disease. However, the diagnosis and treatment of cancer is very distressing. Cancer patients frequently suffer from pain, disfigurement, depression, fatigue, physical dysfunctions, frequent visits to doctors and hospitals, multiple tests and procedures with the possibility of treatment complications, and the financial impact of the diagnosis on their life. This book presents a number of ways that can help cancer patients to look, feel and become healthier, take care of specific symptoms such as hair loss, arm swelling, and shortness of breath, and improve their intimacy, sexuality, and fertility

Full Issue: Volume 15, Number 2, Spring 2022

Complete .pdf file of Volume 15, Number 2 of The Science Journal of the Lander College of Arts and Sciences. Published Spring 2022

A Textbook of Advanced Oral and Maxillofacial Surgery

The scope of OMF surgery has expanded; encompassing treatment of diseases, disorders, defects and injuries of the head, face, jaws and oral cavity. This internationally-recognized specialty is evolving with advancements in technology and instrumentation. Specialists of this discipline treat patients with impacted teeth, facial pain, misaligned jaws, facial trauma, oral cancer, cysts and tumors; they also perform facial cosmetic surgery and place dental implants. The contents of this volume essentially complements the volume 1; with chapters that cover both basic and advanced concepts on complex topics in oral and maxillofacial surgery