SENSORY AND PERCEPTUAL CODES IN CORTICAL AUDITORY PROCESSING

A key aspect of human auditory cognition is establishing efficient and reliable representations about the acoustic environment, especially at the level of auditory cortex. Since the inception of encoding models that relate sound to neural response, three longstanding questions remain open. First, on the apparently insurmountable problem of fundamental changes to cortical responses depending on certain categories of sound (e.g. simple tones versus environmental sound). Second, on how to integrate inner or subjective perceptual experiences into sound encoding models, given that they presuppose existing, direct physical stimulation which is sometimes missed. And third, on how does context and learning fine-tune these encoding rules, as adaptive changes to improve impoverished conditions particularly important for communication sounds. In this series, each question is addressed by analysis of mappings from sound stimuli delivered-to and/or perceived-by a listener, to large-scale cortically-sourced response time series from magnetoencephalography. It is first shown that the divergent, categorical modes of sensory coding may unify by exploring alternative acoustic representations other than the traditional spectrogram, such as temporal transient maps. Encoding models of either of artificial random tones, music, or speech stimulus classes, were substantially matched in their structure when represented from acoustic energy increases –consistent with the existence of a domain-general common baseline processing stage. Separately, the matter of the perceptual experience of sound via cortical responses is addressed via stereotyped rhythmic patterns normally entraining cortical responses with equal periodicity. Here, it is shown that under conditions of perceptual restoration, namely cases where a listener reports hearing a specific sound pattern in the midst of noise nonetheless, one may access such endogenous representations in the form of evoked cortical oscillations at the same rhythmic rate. Finally, with regards to natural speech, it is shown that extensive prior experience over repeated listening of the same sentence materials may facilitate the ability to reconstruct the original stimulus even where noise replaces it, and to also expedite normal cortical processing times in listeners. Overall, the findings demonstrate cases by which sensory and perceptual coding approaches jointly continue to expand the enquiry about listeners’ personal experience of the communication-rich soundscape

Nitric oxide signalling in the inferior colliculus

PhD ThesisThis thesis investigates the distribution and function of neuronal nitric oxide synthase (nNOS) in the inferior colliculus (IC) the principal midbrain nucleus in the auditory pathway. Firstly, experiments using immunocytochemistry and fluorescent microscopy in the rat IC showed two, previously unreported, different subcellular distributions of nNOS in the IC. Secondly, the presence of nNOS positive post-synaptic puncta in the central nucleus suggests that nNOS, contrary to previous reports, is not limited to the IC cortices. Expression of nNOS was observed in both glutamatergic and GABAergic cells. Cells expressing nNOS were shown to often contain calbindin or parvalbumin but rarely calretinin. In vivo electrophysiological experiments were conducted in the anaesthetised guinea pig. Recording of multiunit neuronal activity was combined with local reverse microdialysis of drugs in the IC. Dialysis of NMDA increased both spontaneous and sound driven activity in the IC in a dose dependent manner. These effects were blocked when NMDA was paired with L-MeArg, a NOS inhibitor, or ODQ, a soluble guanylate cyclase (sGC) inhibitor. These results suggest that NMDA receptor-mediated effects in the IC involve NO and its action on sGC. Systemic administration of sodium salicylate, a drug known to induce tinnitus, resulted in a doubling of spontaneous activity in the IC. In contrast, local delivery of salicylate in the IC reduced spontaneous activity in a time/concentration-dependent manner. Both locally and systemically administered salicylate influenced sound driven activity, suggesting these effects are, in part, mediated directly within the IC. No effect of L-MeArg was observed on the salicylate mediated effects, but this could be due to methodological issues. These results demonstrate that NO play plays a role in sound processing in the IC and further work is required to establish its functional significance

Cognición y representación interna de entornos dinámicos en el cerebro de los mamíferos

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 07/05/2021El tiempo es una de las dimensiones fundamentales de la realidad. Paradójicamente, los fenómenos temporales del mundo natural contienen ingentes cantidades de información redundante, y a pesar de ello, codificar internamente el tiempo en el cerebro es imprescindible para anticiparse a peligros en ambientes dinámicos. No obstante, dedicar grandes cantidades de recursos cognitivos a procesar las características espacio-temporales de entornos complejos debería ser incompatible con la supervivencia, que requiere respuestas rápidas. Aun así, los animales son capaces de tomar decisiones en intervalos de tiempo muy estrechos. ¿Cómo consigue hacer esto el cerebro? Como respuesta al balance entre complejidad y velocidad, la hipótesis de la compactación del tiempo propone que el cerebro no codifica el tiempo explícitamente, sino que lo integra en el espacio. En teoría, la compactación del tiempo simplifica las representaciones internas del entorno, reduciendo significativamente la carga de trabajo dedicada a la planificación y la toma de decisiones. La compactación del tiempo proporciona un marco operativo que pretende explicar cómo las situaciones dinámicas, percibidas o producidas, se representan cognitivamente en forma de predicciones espaciales o representaciones internas compactas (CIR), que pueden almacenarse en la memoria y recuperarse más adelante para generar respuestas. Aunque la compactación del tiempo ya ha sido implementada en robots, hasta ahora no se había comprobado su existencia como mecanismo biológico y cognitivo en el cerebro...Time is one of the most prominent dimensions that organize reality. Paradoxically, there are loads of redundant information contained within the temporal features of the natural world, and yet internal coding of time in the brain seems to be crucial for anticipating time-changing, dynamic hazards. Allocating such significant brain resources to process spatiotemporal aspects of complex environments should apparently be incompatible with survival, which requires fast and accurate responses. Nonetheless, animals make decisions under pressure and in narrow time windows. How does the brain achieve this? An effort to resolve the complexity-velocity trade-off led to a hypothesis called time compaction, which states the brain does not encode time explicitly but embeds it into space. Theoretically, time compaction can significantly simplify internal representations of the environment and hence ease the brain workload devoted to planning and decision-making. Time compaction also provides an operational framework that aims to explain how perceived and produced dynamic situations are cognitively represented, in the form of spatial predictions or compact internal representations (CIRs) that can be stored in memory and be used later on to guide behaviour and generate action. Although successfully implemented in robots, time compaction still lacked assessment of its biological soundness as an actual cognitive mechanism in the brain...Fac. de Ciencias BiológicasTRUEunpu

IST Austria Thesis

The hippocampus is a key brain region for memory and notably for spatial memory, and is needed for both spatial working and reference memories. Hippocampal place cells selectively discharge in specific locations of the environment to form mnemonic represen tations of space. Several behavioral protocols have been designed to test spatial memory which requires the experimental subject to utilize working memory and reference memory. However, less is known about how these memory traces are presented in the hippo campus, especially considering tasks that require both spatial working and long -term reference memory demand. The aim of my thesis was to elucidate how spatial working memory, reference memory, and the combination of both are represented in the hippocampus. In this thesis, using a radial eight -arm maze, I examined how the combined demand on these memories influenced place cell assemblies while reference memories were partially updated by changing some of the reward- arms. This was contrasted with task varian ts requiring working or reference memories only. Reference memory update led to gradual place field shifts towards the rewards on the switched arms. Cells developed enhanced firing in passes between newly -rewarded arms as compared to those containing an unchanged reward. The working memory task did not show such gradual changes. Place assemblies on occasions replayed trajectories of the maze; at decision points the next arm choice was preferentially replayed in tasks needing reference memory while in the pure working memory task the previously visited arm was replayed. Hence trajectory replay only reflected the decision of the animal in tasks needing reference memory update. At the reward locations, in all three tasks outbound trajectories of the current arm were preferentially replayed, showing the animals’ next path to the center. At reward locations trajectories were replayed preferentially in reverse temporal order. Moreover, in the center reverse replay was seen in the working memory task but in the other tasks forward replay was seen. Hence, the direction of reactivation was determined by the goal locations so that part of the trajectory which was closer to the goal was reactivated later in an HSE while places further away from the goal were reactivated earlier. Altogether my work demonstrated that reference memory update triggers several levels of reorganization of the hippocampal cognitive map which are not seen in simpler working memory demand s. Moreover, hippocampus is likely to be involved in spatial decisions through reactivating planned trajectories when reference memory recall is required for such a decision

Analog VLSI Circuits for Biosensors, Neural Signal Processing and Prosthetics

Stroke, spinal cord injury and neurodegenerative diseases such as ALS and Parkinson's debilitate their victims by suffocating, cleaving communication between, and/or poisoning entire populations of geographically correlated neurons. Although the damage associated with such injury or disease is typically irreversible, recent advances in implantable neural prosthetic devices offer hope for the restoration of lost sensory, cognitive and motor functions by remapping those functions onto healthy cortical regions. The research presented in this thesis is directed toward developing enabling technology for totally implantable neural prosthetics that could one day restore lost sensory, cognitive and motor function to the victims of debilitating neural injury or disease. There are three principal components to this work. First, novel integrated biosensors have been designed and implemented to transduce weak extra-cellular electrical potentials and optical signals from cells cultured directly on the surface of the sensor chips, as well as to manipulate cells on the surface of these chips. Second, a method of detecting and identifying stereotyped neural signals, or action potentials, has been mapped into silicon circuits which operate at very low power levels suitable for implantation. Third, as one small step towards the development of cognitive neural implants, a learning silicon synapse has been implemented and a neural network application demonstrated. The original contributions of this dissertation include: * A contact image sensor that adapts to background light intensity and can asynchronously detect statistically significant optical events in real-time; * Programmable electrode arrays for enhanced electrophysiological recording, for directing cellular growth, for site-specific in situ bio-functionalization, and for analyte and particulate collection; * Ultra-low power, programmable floating gate template matching circuits for the detection and classification of neural action potentials; * A two transistor synapse that exhibits spike timing dependent plasticity and can implement adaptive pattern classification and silicon learning

How does the brain extract acoustic patterns? A behavioural and neural study

In complex auditory scenes the brain exploits statistical regularities to group sound elements into streams. Previous studies using tones that transition from being randomly drawn to regularly repeating, have highlighted a network of brain regions involved during this process of regularity detection, including auditory cortex (AC) and hippocampus (HPC; Barascud et al., 2016). In this thesis, I seek to understand how the neurons within AC and HPC detect and maintain a representation of deterministic acoustic regularity. I trained ferrets (n = 6) on a GO/NO-GO task to detect the transition from a random sequence of tones to a repeating pattern of tones, with increasing pattern lengths (3, 5 and 7). All animals performed significantly above chance, with longer reaction times and declining performance as the pattern length increased. During performance of the behavioural task, or passive listening, I recorded from primary and secondary fields of AC with multi-electrode arrays (behaving: n = 3), or AC and HPC using Neuropixels probes (behaving: n = 1; passive: n = 1). In the local field potential, I identified no differences in the evoked response between presentations of random or regular sequences. Instead, I observed significant increases in oscillatory power at the rate of the repeating pattern, and decreases at the tone presentation rate, during regularity. Neurons in AC, across the population, showed higher firing with more repetitions of the pattern and for shorter pattern lengths. Single-units within AC showed higher precision in their firing when responding to their best frequency during regularity. Neurons in AC and HPC both entrained to the pattern rate during presentation of the regular sequence when compared to the random sequence. Lastly, development of an optogenetic approach to inactivate AC in the ferret paves the way for future work to probe the causal involvement of these brain regions

Coordinated memory processing between the dorsal and ventral hippocampus and the nucleus accumbens

The brain’s ability to associate experiences with subsequent rewards is fundamental to learning and memory and critical for animal survival. The neural substrates of this process are only partially understood, but are thought to rely on interactions between the hippocampus and nucleus accumbens (NAc). In particular, hippocampal input to the NAc is thought to be crucial for learning and remembering links between spatial information and reward. Hippocampal projections to the NAc arise from both the ventral hippocampus (vH) and the dorsal hippocampus (dH), and studies using optogenetic interventions have demonstrated that either vH or dH input to the NAc can support behaviors dependent on spatial-reward associations. It remains unclear, however, whether dH, vH, or both coordinate memory processing of spatial-reward information in the hippocampal-NAc circuit under normal conditions. Moreover, as dH and vH are thought to encode different aspects of an experience, whether the hippocampus can compartmentalize different types of information to circuits in the NAc is unknown. Times of memory reactivation within and outside the hippocampus are marked by hippocampal sharp-wave ripples (SWRs), discrete events which facilitate investigation of inter-regional information processing. It is unknown whether dH and vH SWRs act in concert or separately to engage NAc neuronal networks, and whether either dH or vH SWRs are preferentially linked to spatial-reward representations. To address these questions, we performed simultaneous extracellular recordings using multi-tetrode arrays in the dH, vH, and NAc of rats learning and performing an appetitive spatial task and during sleep. We report that dH and vH SWRs occur asynchronously, and that individual NAc neurons activated during SWRs from one subdivision of the hippocampus are typically suppressed or unmodulated during SWRs from the other. Furthermore, NAc neurons activated during dH versus vH SWRs show markedly different task-related firing patterns, with NAc representations related to space and reward selectively activated during dH SWRs and not vH SWRs. Our findings reveal that dorsal and ventral hippocampal interactions with the NAc are temporally and anatomically separable at times of memory processing. This work suggests that the dH-NAc and vH-NAc networks provide distinct information channels, with the dH-NAc channel dedicated to linking spatial paths with reward and reward-seeking actions. More broadly, these circuit dynamics could provide a potential neural substrate for the brain’s ability to compartmentalize aspects of experience in memory