L’α-casozépine (α-CZP) est un décapeptide porteur des propriétés anxiolytiques de l’hydrolysat trypsique de caséine αs1 bovine. Différentes propriétés ont pu rapprocher ce peptide de la famille des benzodiazépines, les anxiolytiques les plus prescrits. Cependant, certaines différences, dont notamment une absence d’effets secondaires, permettent aussi de distinguer l’α-CZP des benzodiazépines. Bien que de nombreux éléments laissent penser qu’une action centrale reste l’hypothèse principale du mécanisme d’action de l’α-CZP, aucune régulation de l’activité de zones cérébrales n’avait été montrée jusqu’à présent. Ce travail de thèse aura donc pu montrer que les propriétés anxiolytiques de l’α-CZP sont associées à une modification de l’activité cérébrale chez la souris, après une unique injection intrapéritonéale, dans différentes régions impliquées dans la régulation de l’anxiété, notamment l’amygdale, la formation hippocampale, le noyau accumbens et certains noyaux de l’hypothalamus et du raphé. De plus, ces modifications de l’activité cérébrale ne sont pas exactement les mêmes que celles observées avec le diazépam, une benzodiazépine de référence, ni de celles obtenues avec YLGYL, un peptide dérivé de l’α-CZP, bien qu’il existe des similitudes dans le comportement de l’animal suite aux différents traitements effectués. Enfin, il a été démontré qu’une situation anxiogène est indispensable pour révéler cet effet central. L’ensemble de ce travail aura permis d’avancer dans la compréhension du mode d’action d’un peptide alimentaire ayant des effets positifs sur le comportement et les émotions de son consommateur / Α-casozepine (α-CZP) is a decapeptide that mediates the anxiolytic-like properties of the tryptic hydrolysate of bovine αs1-casein. Different properties of α-CZP leads to consider this peptide close to the benzodiazepine family, the most commonly used anxiolytic molecules. In contrast, other results suggest a distinct mode of action between α-CZP and benzodiazepines, especially the fact that the peptide does not have side effects. Although a central action remains the main hypothesis of the mode of action of α-CZP, no regulation of the brain activity has been shown before. The work achieved in this thesis displayed the fact that the anxiolytic-like properties of α-CZP, after a single intraperitoneal injection of the peptide, are associated with a modulation of cerebral activity in several regions linked to anxiety regulation in mice brains, such as the amygdala, the hippocampal formation, the accumbens nucleus and some nuclei of the hypothalamus or raphe. Besides, these modulations of neural activity are not exactly the same as those obtained after an injection of diazepam, a reference benzodiazepine, or YLGYL, a derivative of α-CZP, even though observed behaviours are similar. Eventually, it has been demonstrated that an anxiety-inducing situation is needed to trigger the central effects of α-CZP. This work allowed a better understanding of the mode of action of a bioactive peptide from alimentary origin that has a positive action on its consumer’s mood and behaviour

<p>The central theme of the present thesis revolves around the exploration of similarities and differences in brain activity patterns invoked by the component processes underlying mnemonic, executive and attentional functions. The primary aim was to identify and functionally characterize commonly recruited brain regions in terms of shared component processes, which has been a largely neglected area of research in cognitive neuroscience. The vast majority of functional brain imaging investigations of cognition has focused on delineating differences between cognitive functions or processes, with the purpose of isolating the unique functional neuroanatomy that underlies specific cognitive domains. By contrast, the present thesis builds on the results from three imaging studies that focused primarily on detecting commonalities in functional brain activity across different forms of memory processes. In study I, the imaging data from two positron emission tomography (PET) experiments were re-analyzed to identify common activation patterns associated with nine different memory tasks incorporated across the experiments, three each separately indexing working memory, episodic memory, and semantic memory. A generic prefrontal cortex (PFC) network involving discrete subregions of the left hemisphere located in ventrolateral (BA 45/47), dorsolateral (BA 9/44/46), and frontopolar (BA 10) sectors of PFC, as well as a midline portion of the frontal lobes, encompassing the dorsal part of the anterior cingulate cortex (ACC) (BA 24/32), was conjointly recruited across all tasks. In study II, we used a novel mixed blocked/event-related functional magnetic resonance imaging (fMRI) design, which enables separation of brain responses associated with different temporal dynamics to further investigate commonalities of neural activation across working memory, episodic memory, semantic memory, and attention/vigilance. A similar set of common PFC regions, as that discovered in Study I, was found to elicit overlapping brain activity across all memory tasks, with a subset of regions also activated in the attention/vigilance task. Furthermore, the task-induced brain activity was dissociated in terms of the temporal profiles of the evoked neural responses. A common pattern of sustained activity seen across all memory tasks and the attention task involved bilateral (predominantly right-lateralized) ventrolateral PFC (BA 45/47), and the dorsal ACC (BA 24/32), which was assumed to reflect general processes of attention/vigilance. A pattern of sustained activity elicited in all memory tasks, in the absence of attention-related activity, involved the right frontopolar cortex (BA 10), which was assumed to reflect control processes underlying task set maintenance. In addition, common transient activation evoked in the memory tasks relative to the attention task was found in the dorsolateral (BA 9/44) and ventrolateral (BA 47) PFC, the superior parietal cortex (BA 7), and cerebellum. In study III, a mixed fMRI design was used to assess the degree of common brain activity associated with increased executive demand, which was independently manipulated within episodic and working memory. Unitary control modulations involved a shared tonic executive component subserved by fronto-striatal-cerebellar circuitry, assumed to govern top-down context processing throughout task periods, and a stimulus-synchronous phasic component mediated by the intraparietal sulcus (BA 7), assumed to support dynamic shifting of the ‘focus of attention’ among internal representations. Collectively, the theoretical implications of shared neural mechanisms are discussed, with a special focus on human memory and its multifaceted relationships with attention and executive control functions. Finally, the presented imaging data are used to outline a tentative hierarchical neurocognitive model that attempts to give an account of how different unitary component processes might work together during cognitive task performance.</p>

The central theme of the present thesis revolves around the exploration of similarities and differences in brain activity patterns invoked by the component processes underlying mnemonic, executive and attentional functions. The primary aim was to identify and functionally characterize commonly recruited brain regions in terms of shared component processes, which has been a largely neglected area of research in cognitive neuroscience. The vast majority of functional brain imaging investigations of cognition has focused on delineating differences between cognitive functions or processes, with the purpose of isolating the unique functional neuroanatomy that underlies specific cognitive domains. By contrast, the present thesis builds on the results from three imaging studies that focused primarily on detecting commonalities in functional brain activity across different forms of memory processes. In study I, the imaging data from two positron emission tomography (PET) experiments were re-analyzed to identify common activation patterns associated with nine different memory tasks incorporated across the experiments, three each separately indexing working memory, episodic memory, and semantic memory. A generic prefrontal cortex (PFC) network involving discrete subregions of the left hemisphere located in ventrolateral (BA 45/47), dorsolateral (BA 9/44/46), and frontopolar (BA 10) sectors of PFC, as well as a midline portion of the frontal lobes, encompassing the dorsal part of the anterior cingulate cortex (ACC) (BA 24/32), was conjointly recruited across all tasks. In study II, we used a novel mixed blocked/event-related functional magnetic resonance imaging (fMRI) design, which enables separation of brain responses associated with different temporal dynamics to further investigate commonalities of neural activation across working memory, episodic memory, semantic memory, and attention/vigilance. A similar set of common PFC regions, as that discovered in Study I, was found to elicit overlapping brain activity across all memory tasks, with a subset of regions also activated in the attention/vigilance task. Furthermore, the task-induced brain activity was dissociated in terms of the temporal profiles of the evoked neural responses. A common pattern of sustained activity seen across all memory tasks and the attention task involved bilateral (predominantly right-lateralized) ventrolateral PFC (BA 45/47), and the dorsal ACC (BA 24/32), which was assumed to reflect general processes of attention/vigilance. A pattern of sustained activity elicited in all memory tasks, in the absence of attention-related activity, involved the right frontopolar cortex (BA 10), which was assumed to reflect control processes underlying task set maintenance. In addition, common transient activation evoked in the memory tasks relative to the attention task was found in the dorsolateral (BA 9/44) and ventrolateral (BA 47) PFC, the superior parietal cortex (BA 7), and cerebellum. In study III, a mixed fMRI design was used to assess the degree of common brain activity associated with increased executive demand, which was independently manipulated within episodic and working memory. Unitary control modulations involved a shared tonic executive component subserved by fronto-striatal-cerebellar circuitry, assumed to govern top-down context processing throughout task periods, and a stimulus-synchronous phasic component mediated by the intraparietal sulcus (BA 7), assumed to support dynamic shifting of the ‘focus of attention’ among internal representations. Collectively, the theoretical implications of shared neural mechanisms are discussed, with a special focus on human memory and its multifaceted relationships with attention and executive control functions. Finally, the presented imaging data are used to outline a tentative hierarchical neurocognitive model that attempts to give an account of how different unitary component processes might work together during cognitive task performance.

Reliable chronic neural recording from focal deep brain structures is impeded by insertion injury and foreign body response, the magnitude of which is correlated with the mechanical mismatch between the electrode and tissue. Thin and flexible neural electrodes cause less glial scarring and record longer than stiff electrodes. However, the insertion of flexible microelectrodes in the brain has been a challenge. A novel insertion method is proposed, and demonstrated, for precise targeting deep brain structures using flexible micro-wire electrodes. A novel electrode guiding system is designed based on the principles governing the buckling strength of electrodes. The proposed guide significantly increases the critical buckling force of the microelectrode. The electrode insertion mechanism involves spinning of the electrode during insertion. The spinning electrode is slowly inserted in the brain through the electrode guide. The electrode guide does not penetrate into cortex. The electrode is inserted in the brain without stiffening it by coating with foreign material or by attaching a rigid support and hence the method is less invasive. Based on two new mechanisms, namely spinning and guided insertion, it is possible to insert ultra-thin micro-wire flexible electrodes in rodent brains without buckling. I have demonstrated successful insertion of 25 µm platinum micro-wire electrodes about 10 mm deep in rat brain. A novel micro-motion compensated ultra-thin flexible platinum microelectrode has been presented for chronic single unit recording. Since manual insertion of the proposed microelectrode is not possible, I have developed a microelectrode insertion device based on the proposed method. A low power low noise 16 channel programmable neural amplifier ASIC has been designed and used to record the neural spikes. The ability to record neural activity during insertion is a unique feature of the developed inserter. In vivo implantation process of the microelectrode has been demonstrated. Microelectrodes were inserted in the Botzinger complex of rat and long term respiratory related neural activity was recorded from live rats. The developed microelectrode has also been used to study brain activity during seizures. In-vivo experimental results show that the proposed method and the prototype insertion system can be used to implant flexible microelectrode in deep brain structures of rodent for brain studies.

Electrical activity is omnipresent throughout the brain, and it varies dependant on the brain region. Areal hierarchy has been suggested to be one of the main principles of the organization of the brain, but there is not a lot of evidence available related to the specialization of the brain’s regions in the temporal domain, that is, how the activity evolves over time. It has been suggested that there is a relationship between spatial location and timescale [1] and that the timescales of neuronal activity in rodents change according to the hierarchical position (derived from anatomical connectivity measurements) of the brain region [2]. Timescale is related to to the capability of a neuron to maintain the same firing rate over a time period. This firing rate can be measured as decay time constant of an auto-correlation matrix of spiking activity, referred to as the timescale of a single neuron [3]. In this thesis, timescales of spontaneous brain activity were measured in eight regions of the mouse prefrontal cortex (PFC) (data obtained in the Carlén Laboratory) and compared to the timescales of eight visual areas (Neuropixels Visual Coding dataset, Allen Institute for Brain Science) [4]. The results showed that cortical regions hold varying timescales, but that there is no clear correspondence of the timescales of spontaneous activity to the anatomical hierarchies. Instead, we show that the PFC regions have a greater variability in their respective timescales compared to visual cortical regions. The analysis was done using two different approaches, where for some regions the measured timescales significantly differs, due to the difference in the use of the magnitudes of the correlation. This work highlights how neuronal timescales measurements can be approached in cortical regions and used for the future work investigating their functional role and the mechanisms of generation of distinct neuronal timescales in the brain. / Elektrisk aktivitet är allestädes närvarande i hela hjärnan, och den varierar beroende på hjärnregionen. Arealhierarki har föreslagits vara en av huvudprinciperna för hjärnans organisation, men det finns inte mycket bevis tillgängligt relaterat till specialiseringen av hjärnans regioner i den temporala domänen, det vill säga hur aktiviteten utvecklas över tiden . Det har föreslagits att det finns ett samband mellan rumslig plats och tidsskala [1] och att tidsskalorna för neuronal aktivitet hos gnagare ändras beroende på den hierarkiska positionen (härledd från anatomiska anslutningsmätningar) i hjärnregionen [2]. Tidsskala är relaterat till förmågan hos ett neuron att bibehålla samma fyrningshastighet under en tidsperiod. Denna avfyrningshastighet kan mätas som fallstidskonstant för en autokorrelationsmatris av spikaktivitet, kallad tidsskalan för en enda neuron [3]. I denna avhandling mättes tidsskalor för spontan hjärnaktivitet i åtta regioner i musens prefrontala kortex (PFC) (data erhållen av Carlén Laboratory) och jämfört med tidsskalorna för åtta visuella områden (Neuropixels Visual Coding dataset, Allen Institute for Brain Science) [4]. Resultaten visade att kortikala regioner har olika tidsskalor, men att det inte finns någon tydlig överensstämmelse mellan tidsskalorna för spontan aktivitet med de anatomiska hierarkierna. Istället visar vi att PFC-regionerna har större variation i sina respektive tidsskalor jämfört med visuella kortikala regioner. Analysen gjordes med hjälp av två olika tillvägagångssätt, där de uppmätta tidsskalorna för vissa regioner skiljer sig avsevärt på grund av skillnaden i användning av storleken på korrelationen. Detta arbete belyser hur neuronala tidsskalemätningar kan beaktas i kortikala regioner och användas för det framtida arbetet med att undersöka deras funktionella roll och mekanismerna för generering av distinkta neuronala tidsskalor i hjärnan.

<p>Disertacija se se bavi analizom mogućnosti brze, efikasne<br />i pouzdane klasterizacije masivnog skupa neuralnih<br />snimaka na osnovu probabilističkih parametara procenjenih<br />iz obrazaca generisanja akcionih potencijala, tzv.<br />&quot;spajkova&quot;, na izlazu pojedinih neurona. Neuralna<br />aktivnost se grubo može podeliti na periode intezivne,<br />umerene i niske aktivnosti. Shodno tome, predložena je<br />gruba dekompozicija neuralne aktivnosti na tri moda koja<br />odgovaraju navedenim obrascima neuralne aktivnosti, na<br />osnovu dobro poznatog Gilbert-Eliot modela. Modovi su<br />dodatno ra&scaron;članjeni na sopstvena stanja na osnovu osobina sukcesivnih spajkova, omogućujući finiji, kompozitni<br />opis neuralne aktivnosti. Za svaki neuron empirijski se<br />procenjuju probabilistički parametri grube dekompozicije<br />- na osnovu Gilbert-Eliotovog modela i finije dekompozicije<br />- na osnovu sopstvenih stanja modova, obezbeđujući<br />željeni skup deskriptora. Dobijeni deskriptori<br />koriste se kao obeležja nekoliko algoritama klasterizacije<br />nad simuliranim i eksperimentalnim podacima. Za generisanje<br />simuliranih podataka primenjen je jednostavan<br />model za generisanje akcionih potencijala različitih<br />oscilatornih pona&scaron;anja pobuđujućih i blokirajućih kortikalnih<br />neurona. Validacija primene probabilističkih parametara<br />za klasterizaciju rada neurona izvr&scaron;ena je na<br />osnovu estimacije parametera nad generisanim neuralnim<br />odzivima. Eksperimentalni podaci su dobijeni<br />snimanjem kortikografskih signala iz dorzalnog anteriornog<br />cingularanog korteksa i lateralnog prefrontalnog<br />korteksa korteksa budnih rezus majmuna. U okviru predloženog<br />protokola evaluacije različitih pristupa<br />klasterizacije testirano je nekoliko metoda. Klasterizacija<br />zasnovana na akumulaciji dokaza iz ansambla particija<br />dobijenih k-means klasterovanjem dala je najstabilnije<br />grupisanje neuralnih jedinica uz brzu i efikasnu implementaciju.<br />Predložena empirijska karakterizacija može da<br />posluži za identifikaciju korelacije sa spolja&scaron;njim stimulusima,<br />akcijama i pona&scaron;anjem životinja u okviru<br />eksperimentalne procedure. Prednosti ovog postupka za<br />opis neuralne aktivnosti su brza estimacija i mali skup<br />deskriptora. Računarska efikasnost omogućuje primenu<br />nad obimnim, paralelno snimanim neuralnim podacima u<br />toku snimanja ili u periodima od interesa za identifikaciju<br />aktiviranih i povezanih zona pri određenim aktivnostima.</p> / <p>The advances in extracellular neural recording techniques<br />result in big data volumes that necessitate fast,<br />reliable, and automatic identification of statistically<br />similar units. This study proposes a single framework<br />yielding a compact set of probabilistic descriptors that<br />characterise the firing patterns of a single unit. Probabilistic<br />features are estimated from an inter-spikeinterval<br />time series, without assumptions about the firing distribution or the stationarity. The first level of proposed<br />firing patterns decomposition divides the inter-spike<br />intervals into bursting, moderate and idle firing modes,<br />yielding a coarse feature set. The second level identifies<br />the successive bursting spikes, or the spiking acceleration/<br />deceleration in the moderate firing mode, yielding<br />a refined feature set. The features are estimated from<br />simulated data and from experimental recordings from<br />the lateral prefrontal cortex in awake, behaving rhesus<br />monkeys. An effcient and stable partitioning of neural<br />units is provided by the ensemble evidence accumulation<br />clustering. The possibility of selecting the number of<br />clusters and choosing among coarse and refined feature<br />sets provides an opportunity to explore and compare<br />different data partitions. The estimation of features, if<br />applied to a single unit, can serve as a tool for the firing<br />analysis, observing either overall spiking activity or the<br />periods of interest in trial-to-trial recordings. If applied to<br />massively parallel recordings, it additionally serves as an<br />input to the clustering procedure, with the potential to<br />compare the functional properties of various brain<br />structures and to link the types of neural cells to the<br />particular behavioural states.</p>

Meditation has been practiced around the world for thousands of years and has during the past decade become increasingly popular in the Western world. Meditation can be seen as a form of mental exercise and refers to a family of complex emotional and attentional regulatory practices that involves different attentional, cognitive monitoring and awareness processes. Clinical research on meditation has demonstrated that meditation seem to reduce stress, anxiety, and depression. Recent interest in how meditation affect the human brain and body have lead to an increase in research regarding the neural correlates of meditation, structural changes induced by meditation, and the potential attentional and emotional benefits mediated by meditation. This thesis investigates expert related changes in neural activity, brain structure, and attentional performance induced by focused attention meditation (FAM) and open monitoring meditation (OMM). The research on meditation and the brain is still in its infancy but despite this, there seem to be some converging evidence of meditation’s impact on the human brain and mind. The results from the included studies in this thesis indicates that expert meditators show greater activation in some meditation related brain areas, as well as less activation in other areas when compared to novice meditators. The results also suggest that long-term meditation practice induce some structural changes in the brain and that meditation seem to enhance the practitioners’ attentional control.

La locomotion est une composante fondamentale de la vie animale : elle permet l’accès continu aux ressources nécessaires à la survie ainsi que l’évitement de périls variés. Les milieux naturels comme anthropiques regorgent toutefois d’obstacles s’élevant contre notre progression. Pour l’humain et les autres mammifères terrestres naviguant principalement par la vision, le franchissement efficace de ces obstacles repose critiquement sur la capacité de modifier proactivement le positionnement et la trajectoire des pas en fonction des informations visuelles extraites durant leur approche. Au niveau du système nerveux, cette capacité implique un processus complexe où le traitement des signaux visuels reflétant les paramètres de l’obstacle spécifie un cours d’action sécurisant son franchissement, lequel est ultimement exécuté par des altérations précises à l’activité musculaire. Des études approfondies chez le chat, l’un des modèles animaux les plus développés et investigués vis-à-vis du contrôle locomoteur, ont présentement impliqué deux structures corticales dans ce processus. Le cortex pariétal postérieur contribuerait ainsi à déterminer la position relative de l’obstacle et le cortex moteur primaire serait central à l’exécution des modifications de la démarche. Cependant, notre compréhension du substrat neural impliqué dans la transformation sensorimotrice joignant ces deux étapes est extrêmement limitée. Plusieurs lignes d’évidences, particulièrement dérivées de travaux chez le primate investiguant le contrôle des mouvements volontaires du bras, pointent cependant vers une contribution potentiellement majeure du cortex prémoteur à cette fonction. Cette thèse entreprend de déterminer directement la contribution prémotrice aux modifications de la démarche. Deux études rapportent ainsi l’activité de neurones individuels enregistrés dans deux larges subdivisions du cortex prémoteur, les aires 6iffu et 4delta, chez le chat éveillé accomplissant librement une tâche de négociation d’obstacles sur tapis roulant. Ces études font état de changements d’activité distincts d’une subdivision à l’autre et corrélés à des aspects spécifiques de la tâche, incluant des changements préparatoires liés à l’approche finale de l’obstacle et d’autres liés à une ou plusieurs étapes des ajustements locomoteurs séquentiels entourant sa négociation. Une troisième étude investigue par microstimulation intracorticale la capacité des différentes subdivisions prémotrices du chat à modifier la démarche. Cette étude expose une variété de réponses électromyographiques complexes s’intégrant en phase avec la marche, où plusieurs subdivisions présentent des signatures distinctes d’effets multi-membres contrastant avec l’influence focale du cortex moteur primaire. Chacune de ces trois études est finalement complémentée d’investigations par traçage rétrograde de connexions anatomiques décisives à l’interprétation fonctionnelle des subdivisions investiguées. Ensemble, ces travaux soutiennent et précisent une contribution centrale du cortex prémoteur aux modifications de la démarche sous guidage visuel. D’une part, ils rapportent pour la première fois que l’activité neuronale de multiples subdivisions du cortex prémoteur reflète différentes étapes de la planification locomotrice stipulant les altérations à entreprendre à l’approche d’un obstacle et durant son franchissement. D’autre part, ils révèlent complémentairement que l’activation de ces subdivisions a le pouvoir d’influencer profondément la marche. Les données collectées soulignent finalement plusieurs points de comparaison entre les aires prémotrices du chat et du primate, suggérant un degré d’analogie fonctionnelle extensible à la locomotion humaine. / Locomotion is a fundamental component of animal life: it provides continuous access to the resources necessary for survival as well as the means to elude potential perils. However, both natural and built environments teem with obstacles impeding one’s progress. For humans and other terrestrial mammals navigating primarily through vision, efficiently negotiating these obstacles critically requires the capacity to proactively adapt the positioning and trajectory of each step on the basis of visual information extracted during their approach. In the nervous system, this capacity involves a complex process through which the integration of visual signals reflecting the parameters and location of an obstacle specifies a course of action to ensure its negotiation, Extensive studies in the cat, one of the most common models used to study the neural mechanisms involved in the control of locomotion, have currently implicated two cortical structures to this process. The posterior parietal cortex is suggested to contribute to the determination of the obstacle’s relative position (with respect to the body) while the primary motor cortex is central to the execution of the gait modifications. However, our comprehension of the neural substrate implicated in the sensorimotor transformation linking these defined stages is extremely limited. Several lines of evidence, predominantly derived from work in the primate investigating the voluntary control of arm movements, nonetheless point towards a potentially major contribution of the premotor cortex to this function. This thesis sets out to directly determine the premotor contribution to the control of gait modifications. Two studies report the activity of individual neurons recorded in two large subdivisions of premotor cortex, areas 6iffu and 4delta, in awake cats freely performing an obstacle negotiation task on treadmill. These studies describe distinct changes in activity across subdivisions that correlate with specific aspects of the task, including preparatory changes related to the final approach of the obstacle and others related to one or more stages of the sequential locomotor adjustments surrounding its negotiation. A third study used intracortical microstimulation to investigate the capacity of different premotor subdivisions of the cat to modify gait. This study reveals a variety of complex electromyographic responses that are integrated into the gait cycle. Moreover, several subdivisions show distinct signatures of multi-limb effects that contrast with the focal influence of the primary motor cortex. Each of these three studies is finally complemented by retrograde tracing investigations of anatomical connections critical to the functional interpretation of the subdivisions examined. Together, these studies support and clarify a central contribution of the premotor cortex to the modification of gait under visual guidance. We report for the first time that the neural activity of multiple subdivisions of the premotor cortex reflects different stages of the locomotor plan specifying the gait alterations to perform during the approach and crossing of an obstacle. In addition, we reveal that activation of these subdivisions has the power to profoundly influence walking. The data collected finally highlight several points of comparison between the premotor areas of the cat and the primate, suggesting a degree of functional analogy extensible to human locomotion.

Numerous studies demonstrate that moment-to-moment neural variability is behaviorally relevant and beneficial for tasks and behaviors requiring cognitive flexibility. However, it remains unclear whether the positive effect of neural variability also holds for cognitive persistence. Moreover, different brain variability measures have been used in previous studies, yet comparisons between them are lacking. In the current study, we examined the association between resting-state BOLD signal variability and two metacontrol policies (i.e., persistence vs. flexibility). Brain variability was estimated from resting-state fMRI (rsfMRI) data using two different approaches (i.e., Standard Deviation (SD), and Mean Square Successive Difference (MSSD)) and metacontrol biases were assessed by three metacontrol-sensitive tasks. Results showed that brain variability measured by SD and MSSD was highly positively related. Critically, higher variability measured by MSSD in the attention network, parietal and frontal network, frontal and ACC network, parietal and motor network, and higher variability measured by SD in the parietal and motor network, parietal and frontal network were associated with reduced persistence (or greater flexibility) of metacontrol (i.e., larger Stroop effect or worse RAT performance). These results show that the beneficial effect of brain signal variability on cognitive control depends on the metacontrol states involved. Our study highlights the importance of temporal variability of rsfMRI activity in understanding the neural underpinnings of cognitive control.

In dieser Arbeit werden zwei wesentliche neue Ergebnisse vorgestellt. Das erste bezieht sich auf die olfaktorische Kodierung und das zweite auf das sensorische Gedaechtnis. Beide Phaenomene werden am Beispiel des Gehirns der Honigbiene untersucht. In Bezug auf die olfaktorische Kodierung zeige ich, dass die neuronale Dynamik waehrend der Stimulation im Antennallobus duftspezifische Trajektorien beschreibt, die in duftspezifischen Attraktoren enden. Das Zeitinterval, in dem diese Attraktoren erreicht werden, betraegt unabhaengig von der Identitaet und der Konzentration des Duftes ungefaehr 800 ms. Darueber hinaus zeige ich, dass Support-Vektor Maschinen, und insbesondere Perzeptronen, ein realistisches und biologisches Model der Wechselwirkung zwischen dem Antennallobus (dem kodierenden Netwerk) und dem Pilzkoerper (dem dekodierenden Netzwerk) darstellen. Dieses Model kann sowohl Reaktionszeiten von ca. 300 ms als auch die Invarianz der Duftwahrnehmung gegenueber der Duftkonzentration erklaeren. In Bezug auf das sensorische Gedaechtnis zeige ich, dass eine einzige Stimulation ohne Belohnung dem Hebbschen Postulat folgend Veraenderungen der paarweisen Korrelationen zwischen Glomeruli induziert. Ich zeige, dass diese Veranderungen der Korrelationen bei 2/3 der Bienen ausreichen, um den letzten Stimulus zu bestimmen. In der zweiten Minute nach der Stimulation ist eine erfolgreiche Bestimmung des Stimulus nur bei 1/3 der Bienen moeglich. Eine Hauptkomponentenanalyse der spontanen Aktivitaet laesst erkennen, dass das dominante Muster des Netzwerks waehrend der spontanen Aktivitaet nach, aber nicht vor der Stimulation das duftinduzierte Aktivitaetsmuster bei 2/3 der Bienen nachbildet. Man kann deshalb die duftinduzierten (Veraenderungen der) Korrelationen als Spuren eines Kurzzeitgedaechtnisses bzw. als Hebbsche "Reverberationen" betrachtet werden. / Two major novel results are reported in this work. The first concerns olfactory coding and the second concerns sensory memory. Both phenomena are investigated in the brain of the honeybee as a model system. Considering olfactory coding I demonstrate that the neural dynamics in the antennal lobe describe odor-specific trajectories during stimulation that converge to odor-specific attractors. The time interval to reach these attractors is, regardless of odor identity and concentration, approximately 800 ms. I show that support-vector machines and, in particular perceptrons provide a realistic and biological model of the interaction between the antennal lobe (coding network) and the mushroom body (decoding network). This model can also account for reaction-times of about 300 ms and for concentration invariance of odor perception. Regarding sensory memory I show that a single stimulation without reward induces changes of pairwise correlation between glomeruli in a Hebbian-like manner. I demonstrate that those changes of correlation suffice to retrieve the last stimulus presented in 2/3 of the bees studied. Succesful retrieval decays to 1/3 of the bees within the second minute after stimulation. In addition, a principal-component analysis of the spontaneous activity reveals that the dominant pattern of the network during the spontaneous activity after, but not before stimulation, reproduces the odor-induced activity pattern in 2/3 of the bees studied. One can therefore consider the odor-induced (changes of) correlation as traces of a short-term memory or as Hebbian reverberations.