abstract: Prosthetic users abandon devices due to difficulties performing tasks without proper graded or interpretable feedback. The inability to adequately detect and correct error of the device leads to failure and frustration. In advanced prostheses, peripheral nerve stimulation can be used to deliver sensations, but standard schemes used in sensorized prosthetic systems induce percepts inconsistent with natural sensations, providing limited benefit. Recent uses of time varying stimulation strategies appear to produce more practical sensations, but without a clear path to pursue improvements. This dissertation examines the use of physiologically based stimulation strategies to elicit sensations that are more readily interpretable. A psychophysical experiment designed to investigate sensitivities to the discrimination of perturbation direction within precision grip suggests that perception is biomechanically referenced: increased sensitivities along the ulnar-radial axis align with potential anisotropic deformation of the finger pad, indicating somatosensation uses internal information rather than environmental. Contact-site and direction dependent deformation of the finger pad activates complimentary fast adapting and slow adapting mechanoreceptors, exhibiting parallel activity of the two associate temporal patterns: static and dynamic. The spectrum of temporal activity seen in somatosensory cortex can be explained by a combined representation of these distinct response dynamics, a phenomenon referred in this dissertation to “biphasic representation.” In a reach-to-precision-grasp task, neurons in somatosensory cortex were found to possess biphasic firing patterns in their responses to texture, orientation, and movement. Sensitivities seem to align with variable deformation and mechanoreceptor activity: movement and smooth texture responses align with potential fast adapting activation, non-movement and coarse texture responses align with potential increased slow adapting activation, and responses to orientation are conceptually consistent with coding of tangential load. Using evidence of biphasic representations’ association with perceptual priorities, gamma band phase locking is used to compare responses to peripheral nerve stimulation patterns and mechanical stimulation. Vibrotactile and punctate mechanical stimuli are used to represent the practical and impractical percepts commonly observed in peripheral nerve stimulation feedback. Standard patterns of constant parameters closely mimic impractical vibrotactile stimulation while biphasic patterns better mimic punctate stimulation and provide a platform to investigate intragrip dynamics representing contextual activation. / Dissertation/Thesis / Doctoral Dissertation Biomedical Engineering 2017

Le cerveau présente des fluctuations de son activité qui reflètent différents niveaux d’engagement avec le monde extérieur. Le traitement des stimuli externes n’est pas seulement associé avec une augmentation du métabolisme cérébrale, mais également avec une désactivation importante dans un ensemble des structures spécifiques connus sous le nom de ‘Default-Mode Network’ (DMN, réseau par défaut). Le rôle du DMN reste énigmatique en partie parce que ses corrélats électrophysiologiques et sa dynamique temporelle sont encore mal compris. En utilisant des enregistrements éléctrophysiologiques intracrânien chez le patient épileptique, nous démontrons que la population neuronale de ce réseau montre des suppressions de l’activité gamma (60-140 Hz). Plus important, nous montrons de quelle manière le profil temporale (en millisecondes) et l’amplitude de cette désactivation sont étroitement corrélés avec la difficulté de la tâche et la performance individuelle. Les résultats mettent également en évidence que pendant une tâche attentionnelle, une activation soutenue dans le temps de la bande gamma est présente dans un large réseau, alors que des activations transitoires sont spécifiques aux régions temporale et occipitale. Nos résultats révèlent ainsi un rôle essentiel des mécanismes d’activation et de désactivation des oscillations large bande gamma dans l’exécution d’un comportement orienté vers un but. / The brain displays moment-to-moment activity fluctuations that reflect various levels of engagement with the outside world. Processing external stimuli is not only associated with increased brain metabolism but also with prominent deactivation in specific structures, collectively known as the default-mode network (DMN). The role of the DMN remains enigmatic partly because its electrophysiological correlates and temporal dynamics are still poorly understood. Using unprecedented wide-spread depth recordings in epileptic patients, undergoing intracranial EEG during pre-surgical evaluation, we reveal that DMN neural populations display task-related suppressions of gamma (60-140 Hz) power and, critically, we show how millisecond temporal profile and amplitude of gamma deactivation tightly correlate with task demands and subject performance. The results show also that during an attentional task, sustained activations in the gamma band power are presented across large cortical networks, while transient activations are mostly specific to occipital and temporal regions. Our findings reveal a pivotal role for broadband gamma modulations in the interplay between activation and deactivation networks mediating efficient goal-directed behavior

The brain displays moment-to-moment activity fluctuations that reflect various levels of engagement with the outside world. Processing external stimuli is not only associated with increased brain metabolism but also with prominent deactivation in specific structures, collectively known as the default-mode network (DMN). The role of the DMN remains enigmatic partly because its electrophysiological correlates and temporal dynamics are still poorly understood. Using unprecedented wide-spread depth recordings in epileptic patients, undergoing intracranial EEG during pre-surgical evaluation, we reveal that DMN neural populations display task-related suppressions of gamma (60-140 Hz) power and, critically, we show how millisecond temporal profile and amplitude of gamma deactivation tightly correlate with task demands and subject performance. The results show also that during an attentional task, sustained activations in the gamma band power are presented across large cortical networks, while transient activations are mostly specific to occipital and temporal regions. Our findings reveal a pivotal role for broadband gamma modulations in the interplay between activation and deactivation networks mediating efficient goal-directed behavior

Background: The visual system may process spatial frequency information in a low-to-high, coarse-to-fine sequence. In particular, low and high spatial frequency information may be processed via different pathways during object recognition, with LSF information projected rapidly to frontal areas and HSF processed later in visual ventral areas. In an electroencephalographic study, we examined the time course of information processing for images filtered to contain different ranges of spatial frequencies. Participants viewed either high spatial frequency (HSF), low spatial frequency (LSF), or unfiltered, broadband (BB) images of objects or nonobject textures, classifying them as showing either man-made or natural objects, or nonobjects. Event-related potentials (ERPs) and evoked and total gamma band activity (eGBA and tGBA) recorded using the electroencephalogram were compared for object and nonobject images across the different spatial frequency ranges. Results: The visual P1 showed independent modulations by object and spatial frequency, while for the N1 these factors interacted. The P1 showed more positive amplitudes for objects than nonobjects, and more positive amplitudes for BB than for HSF images, which in turn evoked more positive amplitudes than LSF images. The peak-to-peak N1 showed that the N1 was much reduced for BB non-objects relative to all other images, while HSF and LSF nonobjects still elicited as negative an N1 as objects. In contrast, eGBA was influenced by spatial frequency and not objecthood, while tGBA showed a stronger response to objects than nonobjects. Conclusions: Different pathways are involved in the processing of low and high spatial frequencies during object recognition, as reflected in interactions between objecthood and spatial frequency in the visual N1 component. Total gamma band seems to be related to a late, probably highlevel representational process.

Active movements are a key feature of human behavior. Even when we do not move our limbs we almost never stop guiding our eyes. As a minimal but omnipresent form of behavior, fast eye movements, called saccades, sample the visual world and determine to a large extent what we perceive. Despite being an integral part of visual perception, prevalent research practice treats the human subject as a passive observer who fixates a spot on the screen and is not allowed to move. Yet, learning sensorimotor interactions by active exploration in order to predict future changes and guide actions seems to be a fundamental principle of neural organization. This results in neural patterns of active behavior that can be fundamentally different from the neural processes revealed in movement-restricted laboratory settings questioning the transferability of results from experimental paradigms demanding fixation to real-world free viewing behavior. In this thesis, we aim at studying the neural mechanisms underlying free viewing behavior. In order to assess the fast, flexible and possibly distributed neural dynamics of active vision, we established a procedure for studying eye movements in magnetoencephalography (MEG) and investigated oscillatory signatures associated with sensorimotor processes of eye movements and saccade target selection, two fundamental processes of active vision. Electroencephalography (EEG) and MEG can non-invasively measure fast neural dynamics and hence seem ideally suited for studying active vision in humans. However, artifacts related to eye movements confound both EEG and MEG signals, and a thorough handling of these artifacts is crucial for investigating neural activities during active movements. Mostly, cleaning of ocular artifacts has been performed for occasional eye movements and blinks in fixation paradigms in EEG. Less is known about the impact of ocular artifacts and especially the saccadic spike on MEG. As a first step to enable active vision studies in MEG, we investigated ocular artifacts and possible ways of their separation from neural signals in MEG. We show that the saccadic spike seriously distorts the spatial and spectral characteristics of the MEG signal (Study 2). We further tested if electrooculogram (EOG) based regression is feasible for corneo-retinal artifact removal (Study 1). Due to an often-raised concern, we addressed if EOG regression eliminates neural activity when applied for MEG. Our results do not indicate such susceptibility and we conclude that EOG regression for removing the corneo-retinal artifact in MEG is suitable. Based on insights from both studies, we established an artifact handling procedure including EOG regression and independent component analysis (ICA) to assess the neural dynamics of active vision. In Study 3, we investigated spectral signatures of neuronal activity across cortex underlying saccade preparation, execution and re-fixation in a delayed saccade task. During preparation and execution, we found a dichotomic signature of gamma power increases and beta power decreases in widespread cortical areas related to saccadic control, including fronto-parietal structures. Saccade direction specific signatures resided in hemisphere lateralized changes in low gamma and alpha power in posterior parietal cortex during preparation extending to extrastriate areas during re-fixation. Real-world behavior implies the constant need to flexibly select actions between competing behavioral alternatives depending on both sensory input and internal states. In order to assess internally motivated viewing behavior, we compared neuronal activity of externally cued saccades with saccades to freely chosen, equally valuable targets. We found gamma band specific power increases in fronto-parietal areas that are likely to reflect a fast transient process of action guidance for sensory-guided saccades and a sustained process for internally selecting between competing behavioral alternatives. The sustained signature of internal action selection suggests that a decision between spatially oriented movements is mediated within sensorimotor structures by neural competition between assemblies encoding parallel evolving movement plans. Since our observations support the assumption that a decision emerges through the distributed consensus of neural activities within effector specific areas rather than in a distinct decision module, they argue for the importance of studying mental processes within their ecologically valid and active context. This thesis shows the feasibility of studying neural mechanisms of active vision in MEG and provides important steps for studying neurophysiological correlates of free viewing in the future. The observed spectrally specific, distributed signatures highlight the importance of assessing fast oscillatory dynamics across the cortex for understanding neural mechanisms mediating real-world active behavior.

Wahrnehmung ist kein vollständig durch sensorische Reize determinierter bottom-up Prozeß, sondern wird stark beeinflußt durch von diesen Reizen unabhängige top-down Prozesse wie etwa Aufmerksamkeit oder Erwartungen. Welche neuronalen Mechanismen liegen der Integration von bottom-up und top-down gerichteter Verarbeitung sensorischer Information zu Grunde? Im ersten Teil dieser Arbeit wurde diese Frage an Hand von Simulationen eines neuronales Netzwerks zweier vereinfachter kortikaler Areale untersucht. Dieses Netzwerk berücksichtigt hierbei jüngste zellphysiologische Befunde über die stark asymmetrischen funktionellen Eigenschaften kortikaler Neurone. Das simulierte Netzwerk repliziert zentrale neurophysiologische Befunde: 1) Top-down Signale erhöhen die Feuerraten der Neurone sowohl in einem hierarchisch hohen als auch tiefen kortikalen Areal. 2) Durch selektive top-down Signale wird die Verarbeitung simultaner Reize zu Gunsten eines faszilitierten Reizes moduliert. 3) Durch die reziproke Netzwerkarchitektur kommt es zu einem bidirektionalen Informationsfluß zwischen Arealen. Diese kooperative Verarbeitung bedingt gemeinsam mit einer nichtlinearen somato-dendritischen Interaktion neuronale Salvenentladungen, die ein hohes Signal-Rausch-Verhältnis aufweisen. Das simulierte Netzwerk demonstriert, welche zentrale Rolle die komplexen nichtlinearen Eigenschaften kortikaler Neurone bei der Integration bottom-up und top-down gerichteter Verarbeitung sensorischer Information spielen. Im Mittelpunkt der im zweiten Abschnitt vorgestellten experimentellen Studie steht die hochfrequente Synchronisation neuronaler Aktivität. Das große neurowissenschaftliche Interesse an der zeitlichen Struktur neuronaler Aktivität liegt insbesondere in der kontrovers diskutierten Hypothese eines „Synchronisationscodes“ begründet, gemäß welcher Information nicht nur durch die Feuerraten kortikaler Neurone, sondern auch durch die Synchronisation der Aktionspotentiale einer Neuronenpopulation codiert wird. Finden sich solche Synchronisationsphänomene in wachen, sich unter möglichst natürlichen Bedingungen verhaltenden Tieren wieder? Sind diese Synchronisationen selektiv für Eigenschaften des Reizes? Gelingt es, an Hand eines objektiven Kriteriums ein funktionelles Frequenzband neuronaler Synchronisation zu definieren? Diese Fragestellungen wurden mittels chronischer extrazellulärer Ableitungen im primären visuellen Kortex wacher, sich verhaltender Katzen untersucht: 1) Visuelle Stimulation induziert einen breitbandigen hochfrequenten Anstieg neuronaler Synchronisation. 2) Diese Synchronisation ist selektiv für die Orientierung visueller Reize. 3) Durch Analyse dieser Stimulusselektivität kann ein funktionelles Band neuronaler Synchronisation von etwa 45 Hz bis 120 Hz definiert werden. Diese Untersuchungen an wachen, sich unter vergleichsweise natürlichen Bedingungen verhaltenden Tieren demonstrieren eine überraschend breite Frequenzverteilung neuronaler Synchronisation, die im hochfrequenten Bereich weit über die üblicherweise untersuchten Frequenzbänder hinausreicht. Diese Befunde sprechen gegen die Hypothese hochfrequenter kortikaler Synchronisation als einem schmalbandigen statischen Phänomen. / Sensory perception is not purely a bottom-up process determined only by sensory stimuli, but is strongly dependent on top-down factors such as attention or expectations.Which neuronal mechanisms underlie the integration of bottom-up and top-down directed processing of sensory information? In the first part of this study this question was addressed by numerical simulations of a neural network model of two simplified cortical areas. The simulated network takes into account recent findings concerning the pronounced functional asymmetry of cortical neurons.The network replicates several important neurophysiological findings: 1) Top-down signals enhance firing rates in hierarchically high and low cortical areas. 2) The processing of two competing stimuli is biased towards one stimulus by selective top-down signals. 3) The reciprocal network architecture results in a bidirectional flow of information. Together with the implemented non-linear somato-dendritic interaction this leads to neuronal bursting behaviour with a high signal to noise ratio. The simulated network demonstrates the critical role of the complex non-linear properties of cortical neurons for the integration of bottom-up and top-down directed sensory processing. The central question of the second part of this study is the functional role of high-frequency synchronization of neuronal activity. The strong interest in the temporal dynamics of neuronal activity is particularly due to the hypothesis of a “synchronization-code” according to which information is not solely encoded by firing rates but also by the synchronization of neuronal ensembles. Is such synchronization observed in awake animals behaving under natural conditions? Are these synchronizations stimulus selective? Is it possible to define a functional frequency band of synchronization based on an objective criterion? These questions were addressed by chronic extracellular recordings of neuronal activity in primary visual cortex of awake behaving cats: 1) Visual stimulation induces neuronal synchronization in a broad and high frequency range. 2) This synchronization is selective for the orientation of a visual stimulus. 3) By analyzing the stimulus selectivity of synchronization a functional band of neuronal synchronization can be defined from about 45 to 120 Hz. These results from animals behaving under natural conditions show a surprisingly broad spectral distribution of synchronization that extends well beyond typically investigated frequency ranges. These results cast doubt on the hypothesis of cortical high-frequency synchronizations as a spectrally sharp and static phenomenon.

Dyslexic and control first-grade school children were compared in a Symbol-to-Sound matching test based on a non-linguistic audiovisual training which is known to have a remediating effect on dyslexia. Visual symbol patterns had to be matched with predicted sound patterns. Sounds incongruent with the corresponding visual symbol (thus not matching the prediction) elicited the N2b and P3a event-related potential (ERP) components relative to congruent sounds in control children. Their ERPs resembled the ERP effects previously reported for healthy adults with this paradigm. In dyslexic children, N2b onset latency was delayed and its amplitude significantly reduced over left hemisphere whereas P3a was absent. Moreover, N2b amplitudes significantly correlated with the reading skills. ERPs to sound changes in a control condition were unaffected. In addition, correctly predicted sounds, that is, sounds that are congruent with the visual symbol, elicited an early induced auditory gamma band response (GBR) reflecting synchronization of brain activity in normal-reading children as previously observed in healthy adults. However, dyslexic children showed no GBR. This indicates that visual symbolic and auditory sensory information are not integrated into a unitary audiovisual object representation in them. Finally, incongruent sounds were followed by a later desynchronization of brain activity in the gamma band in both groups. This desynchronization was significantly larger in dyslexic children. Although both groups accomplished the task successfully remarkable group differences in brain responses suggest that normal-reading children and dyslexic children recruit (partly) different brain mechanisms when solving the task. We propose that abnormal ERPs and GBRs in dyslexic readers indicate a deficit resulting in a widespread impairment in processing and integrating auditory and visual information and contributing to the reading impairment in dyslexia.

In einer Pilotstudie sollten deutschsprachigen Probanden (n=28) in zwei Versuchsabschnitten kurze Sätze sprechen, die das Homonym "Leiter" im Sinne von "Steiggerät" bzw. "Teamchef" näher definieren. Das Homonym sollte am Satzanfang ohne Artikel genannt werden. Das Breitband-EEG (bis 2000 Hz, Zeitkonstante 1,5 s) wurde über F3, F4, C3 und C4 (Intern. 10-20-System) vor und kurz nach Sprachbeginn abgeleitet. Signalepochen des EEG- und Mikrophonsignals von 6 s Dauer wurden gespeichert. Off-line erfolgte die Auswertung der auf Sprachbeginn zentrierten und auf 1 Sekunde gekürzten EEG-Episoden. Es wurden vor Vokalisation motorische Bereitschaftspotentiale gefunden, die im gesamten Zeitbereich (750 ms prä- und 250 ms perireaktiv) wenig strukturiert sind und sich an den vier Ableitorten weder in ihrer Amplitude noch in ihrer Amplituden-Zeit-Struktur unterscheiden. Die Spektralanalyse der EEG-Signalstrecke zeigt unter beiden Versuchsbedingungen eine überproportional hohe Amplitude im [delta]-Band. Mit Hilfe der von Bartsch und Krüger entwickelten Subpotentialanalyse, die im Hochfrequenzbereich des EEG (10-400 Hz) dem "local field potential" ähnliche Phänomene nachweist, konnten in der Signalperiode des Bereitschaftspotentials positive und negative Subpotentiale ermittelt werden. Die Amplitude dieser Subpotentiale liegt zwischen 6 und 12[mycro]V. Der Zeitpunkt des Erscheinens der Subpotentiale wurde als Subpotentialevent (SPe) bezeichnet. Die SPe treten teils gruppiert und teils kohärent auf. Die Intervalle zwischen den SPe wurden histographisch aufgetragen, sie reichen vom 4 bis 15 ms. Auffallendstes Ergebnis war die unterschiedliche Struktur der SPe-Intervallhistogramme, die sich in den linksseitigen Ableitungen anders verhielten als in den rechtsseitigen. Möglicherweise sind diese Differenzen typisch für den eloquenten Unterschied. / During a pilot study, 28 german speeking subjects were supposed in two trial parts to speak in short sentences in order to define the german homonyme "Leiter" with the meaning "leader" respectively "manager". The homonyme should be used without any article at the beginning of the sentence. The EEG-activity (0-2000 Hz, time constant 1,5 sec) was recorded from F3, F4, C3 and C4 (international 10-20-system) before and after starting speech. Signalepochs of EEG-activity and microphone signals of 6 seconds were stored. The offline-evaluation was based on the centered and to the one second shortened EEG-episodes. Before staring speech there had been found a movement-related readines-potential (motor. Bereitschaftspotential), which had been less structured during the whole period of time (750ms pre- and 250 ms perireactive). Neither in their amplitude nor in their amplitude-time-structure distinctions were observed. The spectral analysis of EEG showed an overpropotional high amplitude in [delta]-band under both conditions of the trial. The subpotential-analysis developed by Bartsch and Krüger, which shows similar phenomenons as the "local field potentials" in the high frequency-EEG (10-400 Hz), could show positve and negative subpotentials during the period of the readiness-potential. The amplitudes of those subpotentials lay between 6 and 12[mycro]V. The point of time, when the subpotentials showed up, is called the subpotential-event (SPe). The SPe showed up partly in groups and partly coherent. The intervals between the SPe were put on histographically with a reach from 4 to 25 ms. The most striking result was the varying structure of the histography of the SPe-intervalls. The left-sided histography was conducted differently to the right-sided. May be that these distinctions are typical for the eloquent difference.

L’attention et l’Adaptation Saccadique (AS) sont des composants essentiels de la perception visuelle, le premier renforce le traitement sensoriel des items sélectionnés, le second maintient la précision des mouvements des yeux vers ceux-ci. Ils partagent aussi une dichotomie : les saccades volontaires et l’orientation endogène de l’attention suivent nos buts internes tandis que les saccades réactives et l’orientation exogène répondent aux changements soudains dans l’espace visuel. Leurs substrats neuronaux se superposent en partie. Enfin, chacun impacte l’autre au niveau comportemental. Ce travail de doctorat étudie l’hypothèse d’un couplage fonctionnel entre attention et AS.Toutes nos études chez l’humain sain reposent sur la mesure des performances attentionnelles avant et après l’exposition à l’AS (ou contrôle). Dans la première nous avons exploré les bases neurophysiologiques du couplage réactif/exogène en magnétoencéphalographie. Dans la suivante nous avons comparé l’orientation exogène mesurée par un paradigme de Posner avant et après AS réactive. La dernière, basée sur le même modèle, explorait la modalité volontaire/endogène. Nos résultats montrent que l’AS augmente l’activité oscillatoire gamma et renforce l’orientation de l’attention spatiale. Nous proposons que le couplage repose sur la co-activation de populations neuronales par la plasticité oculomotrice et l’attention au niveau du Cortex Pariétal Postérieur (CPP). Cette activation émerge initialement d’un double effet du cervelet qui inhibe le CPP gauche et active le CPP droit. Cet effet augmente la dominance hémisphérique droite et le biais attentionnel vers la gauche. Notre travail ouvre des perspectives de rééducation des déficits visuo-attentionels / Attention and Saccadic Adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy towards them. Also, a similar dichotomy could be applied to both: voluntary saccades and endogenous attentional shifts follow internal goals while reactive saccades and exogenous shifts are elicited by sudden changes in the environment. Further, their neural substrates partially overlap and they impact each other behaviorally. This PhD work investigates the hypothesis of a functional coupling linking attention and SA in healthy humans. Our experimental contributions all rely on the measurement of attentional performances before and after an exposure to SA (or control). In the first study, we recorded brain magnetic fields to investigate neurophysiological bases of the reactive/exogenous coupling. In the second study, we compared exogenous orienting measured in a Posner-like paradigm before and after reactive SA. Finally, using the same design, the third experiment investigated the voluntary/endogenous modality. We found that SA increased gamma band activity and boosted the orienting of spatial attention. We thus propose that this functional coupling relies on neuronal populations co-activated by both oculomotor plasticity and attention in the Posterior Parietal Cortex (PPC). The initial activation would emerge from a dual effect of the cerebellum inhibiting the left PPC and activating the right PPC. This effect would increase the right hemispheric dominance and the leftward attentional bias. This work opens new perspectives for the rehabilitation of visuoattentional deficits

Χρονοφασματική και χωροχρονική ανάλυση σύγχρονης (φασικά-κλειδωμένης) υψίσυχνης (γ-ζώνης) ταλαντωτικής ηλεκτροεγκεφαλογραφικής δραστηριότητας σε ανώτερης τάξης oπτικογνωστικές αποκρίσεις του ανθρωπίνου εγκεφάλου διεξαγόμενη με το συνεχή μετασχηματισμό του κυματίου και υλοποιούμενη με προηγμένα εργαλεία πληροφορικής της Βιοϊατρικής Μηχανικής στην ψηφιακή επεξεργασία του ΗΕΓ σήματος. / Spectrotemporal and spatiotemporal analysis of synchronous (phase-locked) high-frequency (gamma-band)oscillatory electroencephalographic activity in higher-order visual cognitive responses of the human brain conducted with the continuous wavelet transform and implemented by advanced informatics tools of Biomedical Engineering in digital EEG signal processing.