Noise induced processes in neural systems

Real neurons, and their networks, are far too complex to be described exactly by simple deterministic equations. Any description of their dynamics must therefore incorporate noise to some degree. It is my thesis that the nervous system is organized in such a way that its performance is optimal, subject to this constraint. I further contend that neuronal dynamics may even be enhanced by noise, when compared with their deterministic counter-parts. To support my thesis I will present and analyze three case studies. I will show how noise might (i) extend the dynamic range of mammalian cold-receptors and other cells that exhibit a temperature-dependent discharge; (ii) feature in the perception of ambiguous figures such as the Necker cube; (iii) alter the discharge pattern of single cells

ROLE OF INHIBITION AND SPIKING VARIABILITY IN ORTHO- AND RETRONASAL OLFACTORY PROCESSING

Odor perception is the impetus for important animal behaviors, most pertinently for feeding, but also for mating and communication. There are two predominate modes of odor processing: odors pass through the front of nose (ortho) while inhaling and sniffing, or through the rear (retro) during exhalation and while eating and drinking. Despite the importance of olfaction for an animal’s well-being and specifically that ortho and retro naturally occur, it is unknown whether the modality (ortho versus retro) is transmitted to cortical brain regions, which could significantly instruct how odors are processed. Prior imaging studies show different brain activity for the two modes, even with identical odors. However, odors are first processed via coordinated spiking of neurons in the olfactory bulb (OB) before being relayed downstream to higher cortical regions. Thus, we investigate responses of mitral cells (MC), one of principle neurons in OB, to ortho and retro stimulus to elucidate how the OB processes and codes this information. We analyze our collected in vivo rat data to inform modeling of the OB circuitry and MC responses to both modes of olfaction. Our efforts show that the OB does indeed process odors differently and that the temporal profile of each stimulus route to the OB is crucial for distinguishing ortho and retro odors. Additionally, we detail the rich spiking dynamics observed in our MC model and use a phenomenological model to explain the unexpected non-monotonic spike variability observed as weak-to-moderate background noise increases. Lastly in both anesthetized and awake rodents, we show that MCs with synaptic connections to cortical regions reliably transmit ortho versus retro input stimulus information. Drug manipulation affecting GABAA-mediated synaptic inhibition leads to changes in decoding of ortho/retro and only affects firing response for one of the two modes. We have not only shown that ortho versus retro information is encoded to downstream brain regions, but with models and analysis, we uncover the network dynamics that promote this encoding

The mechanisms of tinnitus: perspectives from human functional neuroimaging

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural substrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power

Predictive coding and stochastic resonance as fundamental principles of auditory phantom perception

Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus—as the prime example of auditory phantom perception—we review recent work at the intersection of artificial intelligence, psychology and neuroscience. In particular, we discuss why everyone with tinnitus suffers from (at least hidden) hearing loss, but not everyone with hearing loss suffers from tinnitus. We argue that intrinsic neural noise is generated and amplified along the auditory pathway as a compensatory mechanism to restore normal hearing based on adaptive stochastic resonance. The neural noise increase can then be misinterpreted as auditory input and perceived as tinnitus. This mechanism can be formalized in the Bayesian brain framework, where the percept (posterior) assimilates a prior prediction (brain’s expectations) and likelihood (bottom-up neural signal). A higher mean and lower variance (i.e. enhanced precision) of the likelihood shifts the posterior, evincing a misinterpretation of sensory evidence, which may be further confounded by plastic changes in the brain that underwrite prior predictions. Hence, two fundamental processing principles provide the most explanatory power for the emergence of auditory phantom perceptions: predictive coding as a top-down and adaptive stochastic resonance as a complementary bottom-up mechanism. We conclude that both principles also play a crucial role in healthy auditory perception. Finally, in the context of neuroscience-inspired artificial intelligence, both processing principles may serve to improve contemporary machine learning techniques

Computational study of resting state network dynamics

Lo scopo di questa tesi è quello di mostrare, attraverso una simulazione con il software The Virtual Brain, le più importanti proprietà della dinamica cerebrale durante il resting state, ovvero quando non si è coinvolti in nessun compito preciso e non si è sottoposti a nessuno stimolo particolare. Si comincia con lo spiegare cos’è il resting state attraverso una breve revisione storica della sua scoperta, quindi si passano in rassegna alcuni metodi sperimentali utilizzati nell’analisi dell’attività cerebrale, per poi evidenziare la differenza tra connettività strutturale e funzionale. In seguito, si riassumono brevemente i concetti dei sistemi dinamici, teoria indispensabile per capire un sistema complesso come il cervello. Nel capitolo successivo, attraverso un approccio ‘bottom-up’, si illustrano sotto il profilo biologico le principali strutture del sistema nervoso, dal neurone alla corteccia cerebrale. Tutto ciò viene spiegato anche dal punto di vista dei sistemi dinamici, illustrando il pionieristico modello di Hodgkin-Huxley e poi il concetto di dinamica di popolazione. Dopo questa prima parte preliminare si entra nel dettaglio della simulazione. Prima di tutto si danno maggiori informazioni sul software The Virtual Brain, si definisce il modello di network del resting state utilizzato nella simulazione e si descrive il ‘connettoma’ adoperato. Successivamente vengono mostrati i risultati dell’analisi svolta sui dati ricavati, dai quali si mostra come la criticità e il rumore svolgano un ruolo chiave nell'emergenza di questa attività di fondo del cervello. Questi risultati vengono poi confrontati con le più importanti e recenti ricerche in questo ambito, le quali confermano i risultati del nostro lavoro. Infine, si riportano brevemente le conseguenze che porterebbe in campo medico e clinico una piena comprensione del fenomeno del resting state e la possibilità di virtualizzare l’attività cerebrale

Connecting the Brain to Itself through an Emulation.

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids. Arrays of modules can be constructed as early stage whole brain emulators, following canonical intra- and inter-regional circuits. By using machine learning algorithms and classic tasks known to activate quasi-orthogonal functional connectivity patterns, bedside testing can rapidly identify ensemble tuning properties and in turn cycle through a sequence of external module architectures to explore which can causatively alter perception and behavior. Whole brain emulation both (1) serves to augment human neural function, compensating for disease and injury as an auxiliary parallel system, and (2) has its independent operation bootstrapped by a human-in-the-loop to identify optimal micro- and macro-architectures, update synaptic weights, and entrain behaviors. In this manner, closed-loop brain-computer interface pilot clinical trials can advance strong artificial intelligence development and forge new therapies to restore independence in children and adults with neurological conditions