Brain-Computer Interfaces using Electrocorticography and Surface Stimulation

The brain connects to, modulates, and receives information from every organ in the body. As such, brain-computer interfaces (BCIs) have vast potential for diagnostics, medical therapies, and even augmentation or enhancement of normal functions. BCIs provide a means to explore the furthest corners of what it means to think, to feel, and to act—to experience the world and to be who you are. This work focuses on the development of a chronic bi-directional BCI for sensorimotor restoration through the use of separable frequency bands for recording motor intent and providing sensory feedback via electrocortical stimulation. Epidural cortical surface electrodes are used to both record electrocorticographic (ECoG) signals and provide stimulation without adverse effects associated with penetration through the protective dural barrier of brain. Chronic changes in electrode properties and signal characteristics are discussed, which inform optimal electrode designs and co-adaptive algorithms for decoding high-dimensional information. Additionally, a multi-layered approach to artifact suppression is presented, which includes a systems-level design of electronics, signal processing, and stimulus waveforms. The results of this work are relevant to a wider range of applications beyond ECoG and BCIs that involve closed-loop recording and stimulation throughout the body. By enabling simultaneous recording and stimulation through the techniques described here, responsive therapies can be developed that are tuned to individual patients and provide precision therapies at exactly the right place and time. This has the potential to improve targeted therapeutic outcomes while reducing undesirable side effects

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

Cogito, ergo sum: An electrophysiological investigation of inner speech properties in a sensory attenuation paradigm

Sensory attenuation describes the decrease in the intensity of sensations we produce ourselves compared to externally-generated sensations, even when elicited by physically identical stimuli. This phenomenon is thought to result from the comparison of sensory predictions to sensory feedback. To predict the sensory consequences of self-initiated actions, duplicates of outgoing motor commands are generated by the motor cortex, known as efference copies. Sensory attenuation is hypothesised to occur if the sensory prediction matches the perceived sensation and has been studied in the context of voluntary actions across many modalities, including auditory. This provides an explanation for why our own speech sounds quieter to us than when we hear someone else speaking the same words. The effect is generated by the suppression of the auditory cortex when producing and hearing self- generated speech compared to when passively listening to a recording of the same speech. Auditory cortex suppression can be measured as an amplitude reduction of the N1 component of the auditory evoked potential. Indeed, a large body of literature shows that smaller N1 amplitudes are elicited by self-generated speech compared to external feedback of the same sound. Analogous sensory attenuation has also been found for the silent production of vowels or words in one's mind–inner speech. This subjective experience of language without any overt articulation plays a fundamental role in various cognitive domains and can be seen as an attenuated version of overt speech. Furthermore, inner speech, as a cognitive phenomenon, engages us in thinking through words and is the foundation for introspection, intricately connected to the philosophical realm of consciousness, ultimately epitomised in René Descartes’ axiom: Cogito, ergo sum ('I think, therefore I am.'). However, the neural processes underlying inner speech and its sensory suppression mechanisms remain largely unexplored. This warrants further investigation of the precision of sensory attenuation elicited by inner speech and whether it carries specific acoustic properties, such as sex, loudness, accent, tempo, rhythm, timbre, etc. Therefore, we first provided a conceptual framework for the subjective and objective assessment of inner speech (Chapter 2). This is followed by an electrophysiological experiment in which participants silently produce two different types of inner phonemes, concurrently with audible phonemes of female and male sex. These overt phonemes either match or do not match the internally produced phoneme of the participant in content (/BA/ versus /BI/) or sex (Chapter 3). We hypothesised that increased acoustic overlap between inner and audible phoneme (identical content or gender) mediated sensory suppression. Our results showed a general N1 amplitude reduction when producing inner speech (active conditions) compared to passive listening of the sample phonemes. However, neither the same content nor the same sex of inner and audible phoneme led to more sensory suppression, compared to non-matching content or sex, respectively. This suggests that inner speech might not precisely encode the content or sex of the perceived voice. Furthermore, we demonstrated in the same sample that other measures of acoustic overlap between inner and audible phonemes, such as peak frequencies in the sound spectrum, known as formants, do not predict the degree of sensory suppression. More specifically, similar formant values of the participant’s individual phoneme (recorded as their overtly uttered syllable) and the audible phoneme did not mediate N1 amplitude reduction (Chapter 4). These two studies suggest that inner speech may contain more impoverished acoustic properties than overt speech that cannot be captured with techniques commonly used in overt speech. Finally, we showed that the early auditory-evoked gamma-band response, another measure of neural activity, did not effectively track sensory attenuation in our data set and experimental paradigm. More specifically, both measured amplitude and inter-trial phase consistency did not differ between the active inner speech and passive listening conditions (Chapter 5). Our findings provide insight into the mechanisms underlying speech-induced sensory attenuation and pave the way for further research of the neural underpinnings of dysfunctional sensory attenuation and auditory-verbal hallucinations in schizophrenia

Quantitative Multimodal Mapping Of Seizure Networks In Drug-Resistant Epilepsy

Over 15 million people worldwide suffer from localization-related drug-resistant epilepsy. These patients are candidates for targeted surgical therapies such as surgical resection, laser thermal ablation, and neurostimulation. While seizure localization is needed prior to surgical intervention, this process is challenging, invasive, and often inconclusive. In this work, I aim to exploit the power of multimodal high-resolution imaging and intracranial electroencephalography (iEEG) data to map seizure networks in drug-resistant epilepsy patients, with a focus on minimizing invasiveness. Given compelling evidence that epilepsy is a disease of distorted brain networks as opposed to well-defined focal lesions, I employ a graph-theoretical approach to map structural and functional brain networks and identify putative targets for removal. The first section focuses on mesial temporal lobe epilepsy (TLE), the most common type of localization-related epilepsy. Using high-resolution structural and functional 7T MRI, I demonstrate that noninvasive neuroimaging-based network properties within the medial temporal lobe can serve as useful biomarkers for TLE cases in which conventional imaging and volumetric analysis are insufficient. The second section expands to all forms of localization-related epilepsy. Using iEEG recordings, I provide a framework for the utility of interictal network synchrony in identifying candidate resection zones, with the goal of reducing the need for prolonged invasive implants. In the third section, I generate a pipeline for integrated analysis of iEEG and MRI networks, paving the way for future large-scale studies that can effectively harness synergy between different modalities. This multimodal approach has the potential to provide fundamental insights into the pathology of an epileptic brain, robustly identify areas of seizure onset and spread, and ultimately inform clinical decision making

Neural correlates of auditory perceptual organization measured with direct cortical recordings in humans

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, September 2011."August, 2011." Vita. Cataloged from PDF version of thesis.Includes bibliographical references.One of the primary functions of the human auditory system is to separate the complex mixture of sound arriving at the ears into neural representations of individual sound sources. This function is thought to be crucial for survival and communication in noisy settings, and allows listeners to selectively and dynamically attend to a sound source of interest while suppressing irrelevant information. How the brain works to perceptually organize the acoustic environment remains unclear despite the multitude of recent studies utilizing microelectrode recordings in experimental animals or non-invasive human neuroimaging. In particular, the role that brain areas outside the auditory cortex might play is, comparatively, vastly understudied. The experiments described in this thesis combined classic behavioral paradigms with electrical recordings made directly from the cortical surface of neurosurgical patients undergoing clinically-indicated invasive monitoring for localization of epileptogenic foci. By sampling from widespread brain areas with high temporal resolution while participants simultaneously engaged in streaming and jittered multi-tone masking paradigms, the present experiments sought to overcome limitations inherent in previous work, namely sampling extent, resolution in time and space, and direct knowledge of the perceptual experience of the listener. In experiment 1, participants listened to sequences of tones alternating in frequency (i.e., ABA-) and indicated whether they perceived the tones as grouped ("1 stream") or segregated ("2 streams"). As has been reported in neurologically-normal listeners since the 1950s, patients heard the sequences as grouped when the frequency separation between the A and B tones was small and segregated when it was large. Evoked potentials from widespread brain areas showed amplitude correlations with frequency separation but surprisingly did not differ based solely on perceptual organization in the absence of changes in the stimuli. In experiment 2, participants listened to sequences of jittered multi-tone masking stimuli on which a regularly-repeating target stream of tones was sometimes superimposed and indicated when they heard the target stream. Target detectability, as indexed behaviorally, increased throughout the course of each sequence. Evoked potentials and high-gamma activity differed strongly based on the listener's subjective perception of the target tones. These results extend and constrain theories of how the brain subserves auditory perceptual organization and suggests several new avenues of research for understanding the neural mechanisms underlying this critical function.by Andrew R. Dykstra.Ph.D

Imaging the spatial-temporal neuronal dynamics using dynamic causal modelling

Oscillatory brain activity is a ubiquitous feature of neuronal dynamics and the synchronous discharge of neurons is believed to facilitate integration both within functionally segregated brain areas and between areas engaged by the same task. There is growing interest in investigating the neural oscillatory networks in vivo. The aims of this thesis are to (1) develop an advanced method, Dynamic Causal Modelling for Induced Responses (DCM for IR), for modelling the brain network functions and (2) apply it to exploit the nonlinear coupling in the motor system during hand grips and the functional asymmetries during face perception. DCM for IR models the time-varying power over a range of frequencies of coupled electromagnetic sources. The model parameters encode coupling strength among areas and allows the differentiations between linear (within frequency) and nonlinear (between-frequency) coupling. I applied DCM for IR to show that, during hand grips, the nonlinear interactions among neuronal sources in motor system are essential while intrinsic coupling (within source) is very likely to be linear. Furthermore, the normal aging process alters both the network architecture and the frequency contents in the motor network. I then use the bilinear form of DCM for IR to model the experimental manipulations as the modulatory effects. I use MEG data to demonstrate functional asymmetries between forward and backward connections during face perception: Specifically, high (gamma) frequencies in higher cortical areas suppressed low (alpha) frequencies in lower areas. This finding provides direct evidence for functional asymmetries that is consistent with anatomical and physiological evidence from animal studies. Lastly, I generalize the bilinear form of DCM for IR to dissociate the induced responses from evoked ones in terms of their functional role. The backward modulatory effect is expressed as induced, but not evoked responses

In your phase: neural phase synchronisation underlies visual imagery of faces

Abstract: Mental imagery is the process through which we retrieve and recombine information from our memory to elicit the subjective impression of “seeing with the mind’s eye”. In the social domain, we imagine other individuals while recalling our encounters with them or modelling alternative social interactions in future. Many studies using imaging and neurophysiological techniques have shown several similarities in brain activity between visual imagery and visual perception, and have identified frontoparietal, occipital and temporal neural components of visual imagery. However, the neural connectivity between these regions during visual imagery of socially relevant stimuli has not been studied. Here we used electroencephalography to investigate neural connectivity and its dynamics between frontal, parietal, occipital and temporal electrodes during visual imagery of faces. We found that voluntary visual imagery of faces is associated with long-range phase synchronisation in the gamma frequency range between frontoparietal electrode pairs and between occipitoparietal electrode pairs. In contrast, no effect of imagery was observed in the connectivity between occipitotemporal electrode pairs. Gamma range synchronisation between occipitoparietal electrode pairs predicted subjective ratings of the contour definition of imagined faces. Furthermore, we found that visual imagery of faces is associated with an increase of short-range frontal synchronisation in the theta frequency range, which temporally preceded the long-range increase in the gamma synchronisation. We speculate that the local frontal synchrony in the theta frequency range might be associated with an effortful top-down mnemonic reactivation of faces. In contrast, the long-range connectivity in the gamma frequency range along the fronto-parieto-occipital axis might be related to the endogenous binding and subjective clarity of facial visual features