A Brain-Machine Interface Instructed by Direct Intracortical Microstimulation

Brain–machine interfaces (BMIs) establish direct communication between the brain and artificial actuators. As such, they hold considerable promise for restoring mobility and communication in patients suffering from severe body paralysis. To achieve this end, future BMIs must also provide a means for delivering sensory signals from the actuators back to the brain. Prosthetic sensation is needed so that neuroprostheses can be better perceived and controlled. Here we show that a direct intracortical input can be added to a BMI to instruct rhesus monkeys in choosing the direction of reaching movements generated by the BMI. Somatosensory instructions were provided to two monkeys operating the BMI using either: (a) vibrotactile stimulation of the monkey's hands or (b) multi-channel intracortical microstimulation (ICMS) delivered to the primary somatosensory cortex (S1) in one monkey and posterior parietal cortex (PP) in the other. Stimulus delivery was contingent on the position of the computer cursor: the monkey placed it in the center of the screen to receive machine–brain recursive input. After 2 weeks of training, the same level of proficiency in utilizing somatosensory information was achieved with ICMS of S1 as with the stimulus delivered to the hand skin. ICMS of PP was not effective. These results indicate that direct, bi-directional communication between the brain and neuroprosthetic devices can be achieved through the combination of chronic multi-electrode recording and microstimulation of S1. We propose that in the future, bidirectional BMIs incorporating ICMS may become an effective paradigm for sensorizing neuroprosthetic devices

Perceptual Strategies and Neuronal Underpinnings underlying Pattern Recognition through Visual and Tactile Sensory Modalities in Rats

The aim of my PhD project was to investigate multisensory perception and multimodal recognition abilities in the rat, to better understand the underlying perceptual strategies and neuronal mechanisms. I have chosen to carry out this project on the laboratory rat, for two reasons. First, the rat is a flexible and highly accessible experimental model, where it is possible to combine state-of-the-art neurophysiological approaches (such as multi-electrode neuronal recordings) with behavioral investigation of perception and (more in general) cognition. Second, extensive research concerning multimodal integration has already been conducted in this species, both at the neurophysiological and behavioral level. My thesis work has been organized in two projects: a psychophysical assessment of object categorization abilities in rats, and a neurophysiological study of neuronal tuning in the primary visual cortex of anaesthetized rats. In both experiments, unisensory (visual and tactile) and multisensory (visuo-tactile) stimulation has been used for training and testing, depending on the task. The first project has required development of a new experimental rig for the study of object categorization in rat, using solid objects, so as to be able to assess their recognition abilities under different modalities: vision, touch and both together. The second project involved an electrophysiological study of rat primary visual cortex, during visual, tactile and visuo-tactile stimulation, with the aim of understanding whether any interaction between these modalities exists, in an area that is mainly deputed to one of them. The results of both of the studies are still preliminary, but they already offer some interesting insights on the defining features of these abilities

Differential modulation of corticospinal excitability during haptic sensing of 2-D patterns vs. textures

<p>Abstract</p> <p>Background</p> <p>Recently, we showed a selective enhancement in corticospinal excitability when participants actively discriminated raised 2-D symbols with the index finger. This extra-facilitation likely reflected activation in the premotor and dorsal prefrontal cortices modulating motor cortical activity during attention to haptic sensing. However, this parieto-frontal network appears to be finely modulated depending upon whether haptic sensing is directed towards material or geometric properties. To examine this issue, we contrasted changes in corticospinal excitability when young adults (n = 18) were engaged in either a roughness discrimination on two gratings with different spatial periods, or a 2-D pattern discrimination of the relative offset in the alignment of a row of small circles in the upward or downward direction.</p> <p>Results</p> <p>A significant effect of task conditions was detected on motor evoked potential amplitudes, reflecting the observation that corticospinal facilitation was, on average, ~18% greater in the pattern discrimination than in the roughness discrimination.</p> <p>Conclusions</p> <p>This differential modulation of corticospinal excitability during haptic sensing of 2-D patterns vs. roughness is consistent with the existence of preferred activation of a visuo-haptic cortical dorsal stream network including frontal motor areas during spatial vs. intensive processing of surface properties in the haptic system.</p

The cognitive neuroscience of prehension: recent developments

Prehension, the capacity to reach and grasp, is the key behavior that allows humans to change their environment. It continues to serve as a remarkable experimental test case for probing the cognitive architecture of goal-oriented action. This review focuses on recent experimental evidence that enhances or modifies how we might conceptualize the neural substrates of prehension. Emphasis is placed on studies that consider how precision grasps are selected and transformed into motor commands. Then, the mechanisms that extract action relevant information from vision and touch are considered. These include consideration of how parallel perceptual networks within parietal cortex, along with the ventral stream, are connected and share information to achieve common motor goals. On-line control of grasping action is discussed within a state estimation framework. The review ends with a consideration about how prehension fits within larger action repertoires that solve more complex goals and the possible cortical architectures needed to organize these actions

Neuronal correlates of tactile working memory in rat barrel cortex and prefrontal cortex

The neuronal mechanisms of parametric working memory \u2013 the short-term storage of graded stimuli to guide behavior \u2013 are not fully elucidated. We have designed a working memory task where rats compare two sequential vibrations, S1 and S2, delivered to their whiskers (Fassihi et al, 2014). Vibrations are a series of velocities sampled from a zero-mean normal distribution. Rats must judge which stimulus had greater velocity standard deviation, \u3c3 (e.g. \u3c31 > \u3c32 turn left, \u3c31 < \u3c32 turn right). A critical operation in this task is to hold S1 information in working memory for subsequent comparison. In an earlier work we uncovered this cognitive capacity in rats (Fassihi et al, 2014), an ability previously ascribed only to primates. Where in the brain is such a memory kept and what is the nature of its representation? To address these questions, we performed simultaneous multi-electrode recordings from barrel cortex \u2013 the entryway of whisker sensory information into neocortex \u2013 and prelimbic area of medial prefrontal cortex (mPFC) which is involved in higher order cognitive functioning in rodents. During the presentation of S1 and S2, a majority of neurons in barrel cortex encoded the ongoing stimulus by monotonically modulating their firing rate as a function of \u3c3; i.e. 42% increased and 11% decreased their firing rate for progressively larger \u3c3 values. During the 2 second delay interval between the two stimuli, neuronal populations in barrel cortex kept a graded representation of S1 in their firing rate; 30% at early delay and 15% at the end. In mPFC, neurons expressed divers coding characteristics yet more than one-fourth of them varied their discharge rate according to the ongoing stimulus. Interestingly, a similar proportion carried the stimulus signal up to early parts of delay period. A smaller but considerable proportion (10%) kept the memory until the end of delay interval. We implemented novel information theoretic measures to quantify the stimulus and decision signals in neuronal responses in different stages of the task. By these measures, a decision signal was present in barrel cortex neurons during the S2 period and during the post stimulus delay, when the animal needed to postpone its action. Medial PFC units also represented animal choice, but later in the trial in comparison to barrel cortex. Decision signals started to build up in this area after the termination of S2. We implemented a regularized linear discriminant algorithm (RDA) to decode stimulus and decision signals in the population activity of barrel cortex and mPFC neurons. The RDA outperformed individual clusters and the standard linear discriminant analysis (LDA). The stimulus and animal\u2019s decision could be extracted from population activity simply by linearly weighting the responses of neuronal clusters. The population signal was present even in epochs of trial where no single cluster was informative. We predicted that coherent oscillations between brain areas might optimize the flow of information within the networks engaged by this task. Therefore, we quantified the phase synchronization of local field potentials in barrel cortex and mPFC. The two signals were coherent at theta range during S1 and S2 and, interestingly, prior to S1. We interpret the pre-stimulus coherence as reflecting top-down preparatory and expectation mechanisms. We showed, for the first time to our knowledge, the neuronal correlates of parametric working memory in rodents. The existence of both positive and negative codes in barrel cortex, besides the representation of stimulus memory and decision signals suggests that multiple functions might be folded into single modules. The mPFC also appears to be part of parametric working memory and decision making network in rats

Funzioni di alto livello nella corteccia somatosensoriale secondaria (SII)

Le proprietà della corteccia somato-sensoriale secondaria (SII) sono state largamente discusse in molteplici studi sia nella scimmia, sia nell’uomo, suggerendo che quest’area assolva funzioni di alto livello nel processamento dello stimolo tattile, quali, ad esempio, l’apprendimento o la memoria. Recentemente, alcuni studi su scimmia hanno evidenziato che, oltre agli stimoli somato-sensoriali, SII risponde anche alla stimolazione dello spazio peri-personale, all’esecuzione di azioni, alla vista di oggetti in movimento ed all’osservazione di azioni, candidando SII ad essere un’area complessa, non limitata a sole funzioni somato-sensoriali. Partendo dallo studio delle risposte di SII agli stimoli tattili, lo scopo di questa tesi è di investigare la risposta di quest’area a stimoli complessi, con particolare attenzione a task di integrazione visuo-tattile e all’osservazione di azioni nell’uomo. Con queste finalità, gli esperimenti presentati sono stati condotti mediante elettroencefalografia stereotassica (stereo-EEG) su pazienti epilettici farmaco-resistenti, impiantati come parte della loro valutazione pre-chirurgica. In una prima fase, sono stati studiati la distribuzione spaziale ed il profilo temporale delle risposte intra-corticali alla stimolazione del nervo mediano controlaterale ed ipsilaterale. I risultati ottenuti indicano che mentre la corteccia somato-sensoriale primaria (SI), il giro precentrale ed il solco intra-parietale rispondono solo alla stimolazione controlaterale, la corteccia somato-sensoriale secondaria e l’insula posteriore sono attivate bilateralmente. Inoltre, queste ultime sono caratterizzate da una risposta tonica e duratura nel tempo. Questa potrebbe rappresentare un meccanismo di ritenzione temporale dell’informazione tattile ed essere l’espressione di funzioni di alto livello quali appunto la memoria e l’apprendimento degli stimoli. Nella seconda sezione della tesi, per testare il possibile coinvolgimento dell’opercolo parietale nell’integrazione visuo-tattile, la stimolazione del nervo mediano controlaterale è stata somministrata congiuntamente ad una stimolazione visiva (i.e. flash). I risultati ottenuti evidenziano un aumento in ampiezza della componente tonica, se comparato alla sola stimolazione tattile, localizzato nell’insula posteriore e nelle porzioni più rostrali dell’opercolo parietale mentre SII mostra un comportamento del tutto inalterato. Tuttavia, tenendo in considerazione che studi su primati non umani riportano risposte visiva in SII a stimoli biologici, sono necessarie ulteriori indagini per comprendere quale tipologia di stimolazione determina l’attivazione di quest’area. Infine, la terza parte della tesi mostra le risposte intra-corticali di SI e SII ad un task motorio che include compiti di afferramento e manipolazione di oggetti, e all’osservazione delle stesse azioni eseguite da un altro individuo. I risultati evidenziano un’attivazione bilaterale di SII, sia durante l’esecuzione sia durante l’osservazione di azioni, con un profilo temporale sincrono. Al contrario SI è attiva solo durante l’esecuzione: l’input a SI durante l’osservazione non ha dunque una natura somato-sensoriale ma piuttosto deve essere sostenuto da un circuito visuo-motorio capace di operare in maniera simultanea. In conclusione, questa tesi dimostra il ruolo cruciale di SII non solo nel processamento degli stimoli tattili ma anche nell’integrazione di stimoli visuo-motori.The somatosensory properties of the second somatosensory cortex (SII) have been largely described by many studies in both monkeys and humans, suggesting for this area a high-order role in tactile stimulation processing with functions including tactile learning and memory. More interestingly, recent studies on monkeys showed that beyond somatosensory stimuli, SII responds to a wider number of stimuli including peripersonal space stimulation, active movements, observation of objects displacement and action observation. Taking into account these results, SII is a candidate to be more than just a somatosensory area. Starting from its somatosensory properties, this thesis aims to disentangle the role of SII in more complex tasks with particular attention to visuo-tactile integration and action observation in humans. To this purpose, the experiments presented in this thesis are carried with stereotactic electroencephalography (stereo-EEG) on drug-resistant epileptic patients to take advantage of its high temporal and spatial resolution. Firstly, I investigated the spatial distribution and the temporal profile of the intracortical responses to both contralateral and ipsilateral median nerve stimulation. Results indicated that while the primary somatosensory area, precentral gyrus and intra-parietal sulcus respond only to the contralateral stimulation, the secondary somatosensory cortex and posterior insula are activated bilaterally. Furthermore, these regions exhibit a tonic long-lasting temporal profile, which might represent a mechanism of temporal retention of the tactile information, and thus be the signature of high-level somatosensory functions such as tactile memory and awareness. In a second stage of the thesis, to test the possible involvement of parietal operculum in visuo-tactile integration, we administered to patients contralateral median nerve stimulation jointly with visual stimulation (i.e. flash) to about 100 drug-resistant epileptic patients. Results underline an enhancement of the tonic components relative to tactile stimulation only, limited to posterior insula and to the rostral areas of parietal operculum, with SII maintaining an unaltered behavior. Considering previous findings in non-human primates, which reported visual responses in SII in response to biological stimuli, further researches are needed to understand which threshold in the stimulus might determine the eventual activation of this area. With this aim, the third part of this thesis presents the intracortical responses of both SI and SII to a motor task requiring reaching, grasping and manipulation, as well as to the observation of the same actions performed by another individual. The results obtained highlighted that SII activates bilaterally, both during the execution and the observation of actions, with a synchronous temporal profile. Conversely, SI activates only during the execution, leading to the conclusion that the input to SII during the observation condition has not a somatosensory nature, but rather that it is sustained by visuo-motor circuits operating simultaneously. Taking together all the evidence, this thesis demonstrates the pivotal role of SII not only in somatosensory functions, as largely reported in literature, but also in the integration of visuo-motor stimuli

Perception of tactile vibrations and a putative neuronal code

We devised a delayed comparison task, appropriate for human and rats, in which subjects discriminate between pairs of vibration delivered either to their whiskers, in rats, or fingertips, in humans, with a delay inserted between the two stimuli. Stimuli were composed of a random time series of velocity values (\u201cnoise\u201d) taken from a Gaussian distribution with 0 mean and standard deviation referred to as \u3c31 for the first stimulus and \u3c32 for the second stimulus. The subject must select a response depending on the two vibrations\u2019 relative standard deviations, \u3c31>\u3c32 or \u3c31<\u3c32. In the standard condition, the base and comparison stimuli both had duration of 400 ms and they were separated by a 800 ms pause. In this condition, humans had better performance than did rats on average, yet the best rats were better than the worst humans. To learn how signals are integrated over time, we varied the duration of the second stimulus. In rats, the performance was progressively improved when the comparison stimulus duration increased from 200 to 400 and then to 600 ms. In humans, the effect of comparison stimulus duration was different: an increase in duration did not improve their performance but biased their choice. Stimuli of longer duration were perceived as having a larger value of \u3c3. We employed a novel psychophysical reverse correlation method to find out which kinematic features of the stochastic stimulus influenced the choices of the subjects. This analysis revealed that rats rely principally on features related to velocity and speed values normalized by stimulus duration \u2013 that is, the rate of velocity and speed features per unit time. In contrast, while human subjects used velocity- and speed-related features, they tended to be influenced by the summated values of those features over time. The summation strategy in humans versus the rate strategy in rats accounts for both (i) the lack of improvement in humans for greater stimulus durations and (ii) the bias by which they judged longer stimuli as having a greater value of \u3c3. Next, we focused on the capacity of rats to accomplish a task of parametric working memory, a capacity until now not found in rodents. For delays between the base and comparison stimuli of up to 6-10 seconds, humans and rats showed similar performance. However when the difference in \u3c3 was small, the rats\u2019 performance began to decay over long inter-stimulus delays more markedly than did the humans\u2019 performance. The next chapter reports the analyses of the activity of barrel cortex neurons during the vibration comparison task. 35% of sampled neuron clusters showed a significant change in firing rate as \u3c3 varied, and the change was positive in every case \u2013 the slope of firing rate versus \u3c3 was positive. We used methods related to signal detection theory to estimate the behavioral performance that could be supported by single neuron clusters and found that the resulting \u201cneurometric\u201d curve was much less steep performance than the psychometric curve (the performance of the whole rat). This led to the notion that stimuli are encoded by larger populations. A general linear model (GLM) that combined multiple simultaneously recorded 2 clusters performed much better than single clusters and began to approach animal performance. We conclude that a potential code for the stimulus is the variation in firing rate according to \u3c3, distributed across large populations.In conclusion, this thesis characterizes the perceptual capacities of humans and rats in a novel working memory task. Both humans and rats can extract the statistical structure of a \u201cnoisy\u201d tactile vibration, but seem to integrate signals by different operations. A major finding is that rats are endowed with a capacity to hold stimulus parameters in working memory with a proficiency that, until now, could be ascribed only to primates. The statistical properties of the stimulus appear to be encoded by a distributed population

Task-related enhancement in corticomotor excitability during haptic sensing with the contra- or ipsilateral hand in young and senior adults

<p>Abstract</p> <p>Background</p> <p>Haptic sensing with the fingers represents a unique class of manipulative actions, engaging motor, somatosensory and associative areas of the cortex while requiring only minimal forces and relatively simple movement patterns. Using transcranial magnetic stimulation (TMS), we investigated task-related changes in motor evoked potential (MEP) amplitude associated with unimanual haptic sensing in two related experiments. In Experiment I, we contrasted changes in the excitability of the hemisphere controlling the task hand in young and old adults under two trial conditions, i.e. when participants either touched a fine grating (<it>smooth trials</it>) or touched a coarse grating to detect its groove orientation (<it>grating trials</it>). In Experiment II, the same contrast between tasks was performed but with TMS applied over the hemisphere controlling the resting hand, while also addressing hemispheric (right vs. left) and age differences.</p> <p>Results</p> <p>In Experiment I, a main effect of <it>trial type </it>on MEP amplitude was detected (p = 0.001), MEPs in the task hand being ~50% larger during grating than smooth trials. No interaction with age was detected. Similar results were found for Experiment II, <it>trial type </it>having a large effect on MEP amplitude in the resting hand (p < 0.001) owing to selective increase in MEP size (~2.6 times greater) for grating trials. No interactions with age or side (right vs. left) were detected.</p> <p>Conclusions</p> <p>Collectively, these results indicate that adding a haptic component to a simple unilateral finger action can elicit robust corticomotor facilitation not only in the working hemisphere but also in the opposite hemisphere. The fact that this facilitation seems well preserved with age, when task difficulty is adjusted, has some potential clinical implications.</p

Temporal structure in neuronal activity during working memory in Macaque parietal cortex

A number of cortical structures are reported to have elevated single unit firing rates sustained throughout the memory period of a working memory task. How the nervous system forms and maintains these memories is unknown but reverberating neuronal network activity is thought to be important. We studied the temporal structure of single unit (SU) activity and simultaneously recorded local field potential (LFP) activity from area LIP in the inferior parietal lobe of two awake macaques during a memory-saccade task. Using multitaper techniques for spectral analysis, which play an important role in obtaining the present results, we find elevations in spectral power in a 50--90 Hz (gamma) frequency band during the memory period in both SU and LFP activity. The activity is tuned to the direction of the saccade providing evidence for temporal structure that codes for movement plans during working memory. We also find SU and LFP activity are coherent during the memory period in the 50--90 Hz gamma band and no consistent relation is present during simple fixation. Finally, we find organized LFP activity in a 15--25 Hz frequency band that may be related to movement execution and preparatory aspects of the task. Neuronal activity could be used to control a neural prosthesis but SU activity can be hard to isolate with cortical implants. As the LFP is easier to acquire than SU activity, our finding of rich temporal structure in LFP activity related to movement planning and execution may accelerate the development of this medical application.Comment: Originally submitted to the neuro-sys archive which was never publicly announced (was 0005002

Processing of relevant information in the primate prefrontal cortex

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1999.Includes bibliographical references.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Extracellular recordings of neural activity were made in areas around and ventral to the principal sulcus of the lateral prefrontal (PF) cortex in two monkeys (macacca mulatta). Activity was assessed during the performance of three visual memory tasks. In the first task, the sensory and mnemonic receptive fields were studied, by requiring monkeys to simultaneously remember both the identity and the location of an object presented at different locations. We report that many conveyed both object and spatial information during the sensory and mnemonic period. Receptive field size was similar during the two periods (10.8 deg. during sensory, 9.3 deg. during mnemonic period). In addition, visual space contralateral to the recording site was preferentially represented. In a second task, the effect of attention on the responses of PF neurons was studied. Visual scenes were presented which contained three objects, only one of which was relevant for behavior. We report that PF neural activity selectively represented information about this relevant object, and activity was often identical to when the relevant object was presented alone. In addition, we describe the time-course of this attentional effect, and show that the relevant object captures PF activity very early, as soon as 140msec after onset of the visual scene. In a third task, the role of PF neurons in a visual-visual association task was assessed. Monkeys were presented with sample objects, and had to choose the test objects that had been associated with them during training after a short delay. The behavior of the monkeys suggested that they were using a prospective strategy to solve this task, i.e. they were recalling the associated visual information soon after sample presentation, and maintaining this in working memory. We report that many neurons showed activity consistent with prospective coding. Examination of the time course of this effect suggests that the recall took place several 100 msec after sample presentation, and that the strongest prospective effects appeared 300-500msec before test object presentation. In conclusion, across these three tasks PF neural activity selectively represented information relevant to immediate behavioral demands.by Gregor Rainer.Ph.D