The role of glyclinergic interneurons in the dorsal column nuclei

[Abstract] The aim of this paper is to provide new insights about the circuitry and the role of the dorsal column nuclei (DCN) in processing somatosensory information. The presence of glycinergic cells, a second type of DCN interneurons in addition to well-known GABAergic interneurons, opens the door to more complex interactions between cuneate cells as well as to a new hypothesis about the computational implications of such interactions. The research posed here fits in a broader context in the field of the sensory systems and deals with the general issue on the role of subcortical structures (i.e the thalamus) in processing sensory information

Brain evolution in bats (Mammalia, Chiroptera): auditory, Olfactory and Sensorimotor systems

Data for brain structure volumes was analysed using multiple regression to test for correlated volumetric evolution in bats (Mammalia, Chiroptera). Significant partial correlations were found between major brain subdivisions, and between structures within the Auditory, Olfactory and Sensonmotor Systems that were predicted to have evolved together on the basis of anatomical connectivity and known functional relationships. Results were clearest in the auditory and sensorimotor systems and weakest for the olfactory system which included many limbic structures. Megachiroptera and microchiroptera were analysed separately; there was good general agreement between the patterns of correlated evolution in both of these clades. When compared to previous studies of con elated volumetric evolution in Insectivores and Primates, it was found that the pattern of correlations found in bats showed features that are unique to the order. These results strongly suggest that brain evolution in bats has proceeded in a mosaic fashion with individual functional systems being the targets of selection

Neuroplasticity induced by peripheral nerve stimulation

PhD ThesisNon-invasive methods have been developed to induce plastic changes in the sensorimotor cortex. These rely on stimulating pairs of afferent nerves. By associative stimulation (AS) of two afferent nerves, excitability changes in the motor cortex occur as indicated by studies reporting changes in motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). Repetitive stimulation of those nerves has a potential in rehabilitation and treatment of neurological disorders like stroke or spinal cord injury. Despite promising results and applications in human subjects using these methods, little is understood about the underlying basis for the changes which are seen. In the present study, behavioural, electrophysiological and immunohistochemical assessments were performed before and after paired associative and non-associative (NAS) median and ulnar nerve stimulation. Two macaque monkeys were trained to perform a skilled finger abduction task using refined behavioural methods. Monkeys were not able to move their thumb and index finger as selectively after one hour of paired AS as indicated by an increased number of errors and decreased performance measures. NAS however decreased error numbers and led to increased performances. Additionally, I recorded from identified pyramidal tract neurons and unidentified cells in primary motor cortex (M1), in two macaque monkeys before and after one hour of AS (and NAS) of the median and ulnar nerve. Cell discharge was recorded in response to electrical stimulation of each nerve independently. Some cells in M1 showed changed firing rates in response to nerve stimulation after AS (and NAS). Subsequently, structural changes in response to one week of paired AS were investigated. The laminar-specific density of parvalbumin-positive interneurons, perineuronal nets and the colocalisation of these two entities changed on the stimulated (in comparison to the non-stimulated) sensorimotor cortex. These findings suggest that the sensorimotor cortex undergoes plastic changes in response to AS (and NAS).Wellcome Trus

Neuromorphic Computing Systems for Tactile Sensing Perception

Touch sensing plays an important role in humans daily life. Tasks like exploring, grasping and manipulating objects deeply rely on it. As such, Robots and hand prosthesis endowed with the sense of touch can better and more easily manipulate objects, and physically collaborate with other agents. Towards this goal, information about touched objects and surfaces has to be inferred from raw data coming from the sensors. The orientation of edges, which is employed as a pre-processing stage in both artificial vision and touch, is a key indication for object discrimination. Inspired on the encoding of edges in human first-order tactile afferents, we developed a biologically inspired, spiking models architecture that mimics human tactile perception with computational primitives that are implementable on low-power subthreshold neuromorphic hardware. The network architecture uses three layers of Leaky Integrate and Fire neurons to distinguish different edge orientations of a bar pressed on the artificial skin of the iCub robot. We demonstrated that the network architecture can learn the appropriate connectivity through unsupervised spike-based learning, and that the number and spatial distribution of sensitive areas within receptive fields are important in edge orientation discrimination. The unconstrained and random structure of the connectivity among layers can produce unbalanced activity in the output neurons, which are driven by a variable amount of synaptic inputs. We explored two different mechanisms of synaptic normalization (weights normalization and homeostasis), defining how this can be useful during the learning phase and inference phase. The network is successfully able to discriminate between 35 orientations of 36 (0 degree to 180 degree with 5 degree step increments) with homeostasis and weights normalization mechanism. Besides edge orientation discrimination, we modified the network architecture to be able to classify six different touch modalities (e.g. poke, press, grab, squeeze, push, and rolling a wheel). We demonstrated the ability of the network to learn appropriate connectivity patterns for the classification, achieving a total accuracy of 88.3 %. Furthermore, another application scenario on the tactile object shapes recognition has been considered because of its importance in robotic manipulation. We illustrated that the network architecture with 2 layers of spiking neurons was able to discriminate the tactile object shapes with accuracy 100 %, after integrating to it an array of 160 piezoresistive tactile sensors where the object shapes are applied

The Change in Fingertip Contact Area as a Novel Proprioceptive Cue

Humans, many animals, and certain robotic hands have deformable fingertip pads [1, 2]. Deformable pads have the advantage of conforming to the objects that are being touched, ensuring a stable grasp for a large range of forces and shapes. Pad deformations change with finger displacements during touch. Pushing a finger against an external surface typically provokes an increase of the gross contact area [3], potentially providing a relative motion cue, a situation comparable to looming in vision [4]. The rate of increase of the area of contact also depends on the compliance of the object [5]. Because objects normally do not suddenly change compliance, participants may interpret an artificially induced variation in compliance, which coincides with a change in the gross contact area, as a change in finger displacement, and consequently they may misestimate their finger’s position relative to the touched object. To test this, we asked participants to compare the perceived displacements of their finger while contacting an object varying pseudo-randomly in compliance from trial to trial. Results indicate a bias in the perception of finger displacement induced by the change in compliance, hence in contact area, indicating that participants interpreted the altered cutaneous input as a cue to proprioception. This situation highlights the capacity of the brain to take advantage of knowledge of the mechanical properties of the body and of the external environment

Development and characterization of an intracortical closed-loop brain-computer interface

Intracortical brain-computer interfaces (BCI) have the potential to restore motor function to people with paralysis by extracting movement intent signals directly from motor cortex. While current technology has allowed individuals to perform simple object interactions with robotic arms, such demonstrations have depended exclusively on visual feedback. Additional forms of sensory feedback may lessen the dependence on vision and allow for more dexterous control. Intracortical microstimulation (ICMS) has been proposed as a method of adding somatosensory feedback to BCI by directly stimulating somatosensory cortex to evoke tactile sensations referred to the hand. Our lab recently demonstrated that ICMS can elicit graded and focal tactile sensations in an individual with spinal cord injury (SCI). However, several challenges must be resolved to demonstrate the viability of ICMS as a technique for incorporating sensory feedback in a closed-loop BCI. First, microstimulation generates large voltage transients that appear as artifacts in the neural recordings used for BCI control. These artifacts can corrupt the recorded signal throughout the entire stimulus train, and must be eliminated to allow for continuous BCI decoding. Second, it is unknown whether the sensations elicited by ICMS can be perceived quickly enough for use as a feedback signal. Here, I present several aspects of the development of a closed-loop BCI system, including a method for artifact rejection and the characterization of simple reaction times to ICMS of human somatosensory cortex. A human participant with tetraplegia due to SCI was implanted with four microelectrode arrays in primary motor and somatosensory cortices. I implemented a robust method of artifact rejection that preserves neural data as soon as 750 microseconds after each stimulus pulse by applying signal blanking and an appropriate digital filter. I validated this method by comparing BCI performance with and without ICMS and found that performance was maintained with ICMS and artifact rejection. Next, I characterized simple reaction times to single-channel ICMS, and found that responses to ICMS were comparable, and often faster, than responses to electrical stimulation on the hand. These findings suggest that ICMS is a viable method to provide feedback in a closed-loop BCI

Physiological studies on the postsynaptic dorsal column system

This thesis has made an electrophysiological study of segmental and descending influences on identified neurones of the postsynaptic dorsal column (p.s.d.c.) system and has examined aspects of the relationship between the neurones of this projection and the spinocervical tract (s.c.t.). Extracellular single unit microelectrode recordings were made from the axons of p.s.d.c. neurones ascending the dorsal columns of cats anaesthetised with chloralose.1) The response properties and organisation of the cutaneous receptive fields of p.s.d.c. neurones were investigated using light tactile, and noxious mechanical and thermal stimuli.The receptive fields of units with input from glabrous skin had a complex organisation and many were discontinuous. These units could be inhibited by both light tactile and noxious cutaneous stimuli. In contrast, units with receptive fields confined to hairy skin of the proximal limb often had a concentric receptive field organisation in which the high threshold excitatory component extended beyond the low threshold area. These units could be inhibited only by light tactile stimuli and their inhibitory receptive fields generally covered an extensive area of skin virtually surrounding the excitatory componentsThese observations are contrasted with the (ii) relatively simple receptive field organisation of s.c.t. neurones and are discussed in relation to previous observations of the morphology and ultrastructure of neurones of the p.s.d.c. and s.c.t. systems.2) A study has been made of the influence of systems descending from the brain on the response properties and receptive field organisation of p.s.d.c. neurones. The cutaneous receptive fields of p.s.d.c. units were investigated both before and during a block of conduction in descending fibres produced by cooling a region of cord rostral to the recording site. The results indicate that both the responsiveness of p.s.d.c. neurones to noxious mechanical and thermal stimuli and the area of skin from which such stimuli may effectively excite these cells are powerfully suppressed by inhibitory controls descending from the brain. The possible functions of these descending actions are discussed.3) The relationship between neurones of the p.s.d.c. and s.c.t. systems has been investigated. Contrary to recent reports in the literature, it was established that p.s.d.c. and s.c.t. projections arise in substantial part, if not entirely, from separate populations of neurones in the dorsal horn. There is, however, a close relationship between the two systems at the level of the dorsal horn. Evidence was obtained to support the suggestion that some s.c.t. cells make effective excitatory collateral connections with p.s.d.c. neurones

Peripheral mechanisms for fine tactile perception: behavioural and modelling approach

The tactile system is highly complex. The properties of its central and peripheral components determine the way external stimuli are transformed into perception. At the very first stage, first-order tactile neurons respond to skin mechanical deformation and their activation convey a representation of the sensed object (i.e., encoding). However, there are several open questions regarding which factors can significantly influence the peripheral neural response and hence, perception. The goal of the work presented in this thesis is to provide new evidence about the link between skin properties, object’s characteristics, first-order tactile neurons response and discriminative judgments. Chapter One provides an overview of the tactile system with a focus on the peripheral components (e.g., skin, first-order tactile neurons), as well as a summary of the relevant behavioural findings on tactile perception in Young and Elderly. Chapter Two outlines the methods used in this work including psychophysics, a device to present tactile stimuli in a controlled fashion, skin measurement techniques, and manufacturing of fine-textured stimuli. Chapter Three provides an in-depth review of computational models that simulate the response of first-order neurons and how they can be applied for psychophysical research. Chapter Four is the first empirical chapter that evaluates the effects of skin and mechanoreceptive afferent properties on spatial tactile sensitivity in young and elderly participants assessed with the 2-point discrimination task. Chapter 5 is the second empirical chapter that investigates the effects of the interaction between finger and surface properties on the detection sensitivity for a single microdot in young participants with active exploration. Chapter Six summarises the findings of the research undertaken in my doctoral studies and discusses their implications for understanding the sensory mechanisms underlying tactile perception. Overall, the findings presented in this thesis suggest that the progressive loss of mechanoafferent units contribute to the decline in tactile spatial acuity as predicted by a population model of the afferent response, and provide new evidence on the complex effects of frictional changes and the role of skin biomechanics on the detection of a microdot

Investigating the Inhibition of the Return of Attention in the Tactile Domain

Purpose: The time-course needed to elicit tactile inhibition of return (IOR) has not been well-defined due to the paucity of research in this area especially studies investigating spatial discrimination. Reportedly tactile IOR uses higher-order mental representations to orient attention spatially yet the properties of low-level dermatomal maps may better account for how IOR orients tactile attention in space although its contribution is unclear. The present study sought to establish a time-course that evokes IOR in a unimodal tactile spatial discrimination task and decouples the contribution of the dermatome from higher-order representations. Methods: Two conditions containing distinct tactile cue-target paradigms designed to tap into either the whole finger representation (Finger trial) and its response gradient or the dermatomal representation (Location trial) were applied to the index and middle finger-tips of both hands of 17 participants. Targets appeared at a cued or uncued finger following an inter-stimulus interval (ISI; 150, 600, or 1200 ms) for Finger trials and they appeared at cued or uncued locations after an ISI within a single finger-tip for Location trials. Results: At ISIs of 1200 ms IOR and facilitation of response times (RTs) were elicited for cued and uncued homologous Finger trials respectively. As ISIs increased, RTs for uncued homologous and adjacent Finger trials linearly decreased and increased respectively. Thus, Finger trial type trends exhibited a non-linear response gradient but they were not different from those of Location trials, specifically cued and uncued Location trials mirrored cued and uncued homologous Finger trials. While no facilitation and IOR occurred between Location trials, cued and uncued trials showed trends typical of IOR. Conclusion: We showed that tactile IOR can be elicited in a unimodal spatial discrimination task and that tactile spatial attention, oriented via IOR, is likely driven by low-level dermatomal maps