Learning Task-Related Activities From Independent Local-Field-Potential Components Across Motor Cortex Layers

Motor cortical microcircuits receive inputs from dispersed cortical and subcortical regions in behaving animals. However, how these inputs contribute to learning and execution of voluntary sequential motor behaviors remains elusive. Here, we analyzed the independent components extracted from the local field potential (LFP) activity recorded at multiple depths of rat motor cortex during reward-motivated movement to study their roles in motor learning. Because slow gamma (30–50 Hz), fast gamma (60–120 Hz), and theta (4–10 Hz) oscillations temporally coordinate task-relevant motor cortical activities, we first explored the behavioral state- and layer-dependent coordination of motor behavior in these frequency ranges. Consistent with previous findings, oscillations in the slow and fast gamma bands dominated during distinct movement states, i.e., preparation and execution states, respectively. However, we identified a novel independent component that dominantly appeared in deep cortical layers and exhibited enhanced slow gamma activity during the execution state. Then, we used the four major independent components to train a recurrent network model for the same lever movements as the rats performed. We show that the independent components differently contribute to the formation of various task-related activities, but they also play overlapping roles in motor learning

Theoretical considerations and supporting evidence for the primary role of source geometry on field potential amplitude and spatial extent

Field potential (FP) recording is an accessible means to capture the shifts in the activity of neuron populations. However, the spatial and composite nature of these signals has largely been ignored, at least until it became technically possible to separate activities from co-activated sources in different structures or those that overlap in a volume. The pathway-specificity of mesoscopic sources has provided an anatomical reference that facilitates transcending from theoretical analysis to the exploration of real brain structures. We review computational and experimental findings that indicate how prioritizing the spatial geometry and density of sources, as opposed to the distance to the recording site, better defines the amplitudes and spatial reach of FPs. The role of geometry is enhanced by considering that zones of the active populations that act as sources or sinks of current may arrange differently with respect to each other, and have different geometry and densities. Thus, observations that seem counterintuitive in the scheme of distance-based logic alone can now be explained. For example, geometric factors explain why some structures produce FPs and others do not, why different FP motifs generated in the same structure extend far while others remain local, why factors like the size of an active population or the strong synchronicity of its neurons may fail to affect FPs, or why the rate of FP decay varies in different directions. These considerations are exemplified in large structures like the cortex and hippocampus, in which the role of geometrical elements and regional activation in shaping well-known FP oscillations generally go unnoticed. Discovering the geometry of the sources in play will decrease the risk of population or pathway misassignments based solely on the FP amplitude or temporal pattern

Olfactory Inputs Modulate Respiration-Related Activity In The Prefrontal Cortex And Fear Behavior

Voluntary control of respiration, especially via rhythmic nasal breathing, alleviates negative feelings such as fear and is used clinically to manage certain types of panic attacks. However, the neural substrates that link nasal breathing to fear circuits remains unknown. Here we show that during conditioned fear-induced freezing behavior, mice breathe at a steady rate (~4 Hz) which is strongly correlated with a predominant 4 Hz oscillation observed in the olfactory bulb and the prelimbic prefrontal cortex (plPFC), a structure critical for the expression of conditioned fear behaviors. We demonstrate anatomical and functional connectivity between the olfactory pathway and plPFC via circuit tracing and optogenetic approaches. Disrupting olfactory inputs significantly reduces the 4 Hz oscillation in the plPFC suggesting that respiration-related signals from the olfactory system play a role in entraining this fear-related signal. Surprisingly, we find that without olfactory inputs, freezing times are significantly prolonged. Collectively, our results indicate that olfactory inputs modulate rhythmic activity in fear circuits and suggest a neural pathway that may underlie the behavioral benefits of respiration-entrained olfactory signals

Uncorrelated bilateral cortical input becomes timed across hippocampal subfields for long waves whereas gamma waves are largely ipsilateral

The role of interhemispheric connections along successive segments of cortico-hippocampal circuits is poorly understood. We aimed to obtain a global picture of spontaneous transfer of activity during non-theta states across several nodes of the bilateral circuit in anesthetized rats. Spatial discrimination techniques applied to bilateral laminar field potentials (FP) across the CA1/Dentate Gyrus provided simultaneous left and right readouts in five FP generators that reflect activity in specific hippocampal afferents and associative pathways. We used a battery of correlation and coherence analyses to extract complementary aspects at different time scales and frequency bands. FP generators exhibited varying bilateral correlation that was high in CA1 and low in the Dentate Gyrus. The submillisecond delays indicate coordination but not support for synaptic dependence of one side on another. The time and frequency characteristics of bilateral coupling were specific to each generator. The Schaffer generator was strongly bilaterally coherent for both sharp waves and gamma waves, although the latter maintained poor amplitude co-variation. The lacunosum-moleculare generator was composed of up to three spatially overlapping activities, and globally maintained high bilateral coherence for long but not short (gamma) waves. These two CA1 generators showed no ipsilateral relationship in any frequency band. In the Dentate Gyrus, strong bilateral coherence was observed only for input from the medial entorhinal areas, while those from the lateral entorhinal areas were largely asymmetric, for both alpha and gamma waves. Granger causality testing showed strong bidirectional relationships between all homonymous bilateral generators except the lateral entorhinal input and a local generator in the Dentate Gyrus. It also revealed few significant relationships between ipsilateral generators, most notably the anticipation of lateral entorhinal cortex toward all others. Thus, with the notable exception of the lateral entorhinal areas, there is a marked interhemispheric coherence primarily for slow envelopes of activity, but not for pulse-like gamma waves, except in the Schafer segment. The results are consistent with essentially different streams of activity entering from and returning to the cortex on each side, with slow waves reflecting times of increased activity exchange between hemispheres and fast waves generally reflecting ipsilateral processing

Data-driven re-referencing of intracranial EEG based on independent component analysis (ICA)

Background: Intracranial recordings from patients implanted with depth electrodes are a valuable source of information in neuroscience. They allow for the unique opportunity to record brain activity with high spatial and temporal resolution. A common pre-processing choice in stereotactic EEG (S-EEG) is to re-reference the data with a bipolar montage. In this, each channel is subtracted from its neighbor, to reduce commonalities between channels and isolate activity that is spatially confined. New Method: We challenge the assumption that bipolar reference effectively performs this task. To extract local activity, the distribution of the signal source of interest, interfering distant signals, and noise need to be considered. Referencing schemes with fixed coefficients can decrease the signal to noise ratio (SNR) of the data, they can lead to mislocalization of activity and consequently to misinterpretation of results. We propose to use Independent Component Analysis (ICA), to derive filter coefficients that reflect the statistical dependencies of the data at hand. Results: We describe and demonstrate this on human S-EEG recordings. In a simulation with real data, we quantitatively show that ICA outperforms the bipolar referencing operation in sensitivity and importantly in specificity when revealing local time series from the superposition of neighboring channels. Comparison with Existing Method: We argue that ICA already performs the same task that bipolar referencing pursues, namely undoing the linear superposition of activity and will identify activity that is local. Conclusions: When investigating local sources in human S-EEG, ICA should be preferred over re-referencing the data with a bipolar montage

Modelling the effects of serotonin on the hippocampal CA1 region during navigation

The mammalian hippocampus is vitally involved in the formation of both episodic memory and semantic memory, and in learning and recognition. These functions are actively involved during spatial navigation through an environment. The rodent hippocampus in particular has been greatly studied, providing a wealth of experimental data; however collation of this data into universally accepted theories of hippocampal function is far from complete. The present study concentrates on events occurring in the rodent hippocampus during such navigation. There is particular emphasis on the hippocampal theta rhythm which is manifested during navigation; on the existence and characteristics of place fields and associated place cells; and on the phenomenon of phase precession. The study has been limited to the CA1 region. Testable assertions are made about these phenomena. These assertions have been incorporated into models which are described in the later chapters of the thesis. The model has been further extended to demonstrate features of serotonergic activity in the CA1 region

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches

Role of the hippocampus in goal representation : Insights from behavioural and electrophysiological approaches

The hippocampus plays an important role in spatial cognition, as supported by the location-specific firing of hippocampal place cells. In random foraging tasks, each place cell fires at a specific position (‘place field’) while other hippocampal pyramidal neurons remain silent. A recent study evidenced a reliable extra-field activity in most CA1 place cells of rats waiting for reward delivery in an uncued goal zone. While the location-specific activity of place cells is thought to underlie a flexible representation of space, the nature of this goal-related signal remains unclear. To test whether hippocampal goal-related activity reflects a representation of goal location or a reward-related signal, we designed a two-goal navigation task in which rats were free to choose between two uncued spatial goals to receive a reward. The magnitude of reward associated to each goal zone was modulated, therefore changing the goal value. We recorded CA1 and CA3 unit activity from rats performing this task. Behaviourally, rats were able to remember each goal location and flexibly adapt their choices to goal values. Electrophysiological data showed that a large majority of CA1-CA3 place and silent cells expressed goal-related activity. This activity was independent from goal value and rats’ behavioural choices. Importantly, a large proportion of cells expressed a goal-related activity at one goal zone only. Altogether, our findings suggest that the hippocampus processes and stores relevant information about the spatial characteristics of the goal. This goal representation could be used in cooperation with structures involved in decision-making to optimise goal-directed navigation