Single Neuron Level Research Articles

Representation of internal speech by single neurons in human supramarginal gyrus

Speech brain–machine interfaces (BMIs) translate brain signals into words or audio outputs, enabling communication for people having lost their speech abilities due to diseases or injury. While important advances in vocalized, attempted and mimed speech decoding have been achieved, results for internal speech decoding are sparse and have yet to achieve high functionality. Notably, it is still unclear from which brain areas internal speech can be decoded. Here two participants with tetraplegia with implanted microelectrode arrays located in the supramarginal gyrus (SMG) and primary somatosensory cortex (S1) performed internal and vocalized speech of six words and two pseudowords. In both participants, we found significant neural representation of internal and vocalized speech, at the single neuron and population level in the SMG. From recorded population activity in the SMG, the internally spoken and vocalized words were significantly decodable. In an offline analysis, we achieved average decoding accuracies of 55% and 24% for each participant, respectively (chance level 12.5%), and during an online internal speech BMI task, we averaged 79% and 23% accuracy, respectively. Evidence of shared neural representations between internal speech, word reading and vocalized speech processes was found in participant 1. SMG represented words as well as pseudowords, providing evidence for phonetic encoding. Furthermore, our decoder achieved high classification with multiple internal speech strategies (auditory imagination/visual imagination). Activity in S1 was modulated by vocalized but not internal speech in both participants, suggesting no articulator movements of the vocal tract occurred during internal speech production. This work represents a proof-of-concept for a high-performance internal speech BMI.

Differential clustering of visual and choice- and saccade-related activity in macaque V3A and CIP.

Neurons in sensory and motor cortices tend to aggregate in clusters with similar functional properties. Within the primate dorsal ("where") pathway, an important interface between three-dimensional (3-D) visual processing and motor-related functions consists of two hierarchically organized areas: V3A and the caudal intraparietal (CIP) area. In these areas, 3-D visual information, choice-related activity, and saccade-related activity converge, often at the single-neuron level. Characterizing the clustering of functional properties in areas with mixed selectivity, such as these, may help reveal organizational principles that support sensorimotor transformations. Here we quantified the clustering of visual feature selectivity, choice-related activity, and saccade-related activity by performing correlational and parametric comparisons of the responses of well-isolated, simultaneously recorded neurons in macaque monkeys. Each functional domain showed statistically significant clustering in both areas. However, there were also domain-specific differences in the strength of clustering across the areas. Visual feature selectivity and saccade-related activity were more strongly clustered in V3A than in CIP. In contrast, choice-related activity was more strongly clustered in CIP than in V3A. These differences in clustering may reflect the areas' roles in sensorimotor processing. Stronger clustering of visual and saccade-related activity in V3A may reflect a greater role in within-domain processing, as opposed to cross-domain synthesis. In contrast, stronger clustering of choice-related activity in CIP may reflect a greater role in synthesizing information across functional domains to bridge perception and action.NEW & NOTEWORTHY The occipital and parietal cortices of macaque monkeys are bridged by hierarchically organized areas V3A and CIP. These areas support 3-D visual transformations, carry choice-related activity during 3-D perceptual tasks, and possess saccade-related activity. This study quantifies the functional clustering of neuronal response properties within V3A and CIP for each of these domains. The findings reveal domain-specific cross-area differences in clustering that may reflect the areas' roles in sensorimotor processing.

Neural signatures of natural behaviour in socializing macaques.

Our understanding of the neurobiology of primate behaviour largely derives from artificial tasks in highly controlled laboratory settings, overlooking most natural behaviours that primate brains evolved to produce1-3. How primates navigate the multidimensional social relationships that structure daily life4 and shape survival and reproductive success5 remains largely unclear at the single-neuron level. Here we combine ethological analysis, computer vision and wireless recording technologies to identify neural signatures of natural behaviour in unrestrained, socially interacting pairs of rhesus macaques. Single-neuron and population activity in the prefrontal and temporal cortex robustly encoded 24 species-typical behaviours, as well as social context. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioural mechanism supporting friendships and alliances6, and neural activity maintained a running account of these social investments. Confronted with an aggressive intruder, behavioural and neural population responses reflected empathy and were buffered by the presence of a partner. Our findings reveal a highly distributed neurophysiological ledger of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.

Ocular surface information seen from the somatosensory thalamus and cortex.

Ocular Surface (OS) somatosensory innervation detects external stimuli producing perceptions, such as pain or dryness, the most relevant symptoms in many OS pathologies. Nevertheless, little is known about the central nervous system circuits involved in these perceptions, and how they integrate multimodal inputs in general. Here, we aim to describe the thalamic and cortical activity in response to OS stimulation of different modalities. Electrophysiological extracellular recordings in anaesthetized rats were used to record neural activity, while saline drops at different temperatures were applied to stimulate the OS. Neurons were recorded in the ophthalmic branch of the trigeminal ganglion (TG, 49 units), the thalamic VPM-POm nuclei representing the face (Th, 69 units) and the primary somatosensory cortex (S1, 101 units). The precise locations for Th and S1 neurons receiving OS information are reported here for the first time. Interestingly, all recorded nuclei encode modality both at the single neuron and population levels, with noxious stimulation producing a qualitatively different activity profile from other modalities. Moreover, neurons responding to new combinations of stimulus modalities not present in the peripheral TG subsequently appear in Th and S1, being organized in space through the formation of clusters. Besides, neurons that present higher multimodality display higher spontaneous activity. These results constitute the first anatomical and functional characterization of the thalamocortical representation of the OS. Furthermore, they provide insight into how information from different modalities gets integrated from the peripheral nervous system into the complex cortical networks of the brain. KEY POINTS: Anatomical location of thalamic and cortical ocular surface representation. Thalamic and cortical neuronal responses to multimodal stimulation of the ocular surface. Increasing functional complexity along trigeminal neuroaxis. Proposal of a new perspective on how peripheral activity shapes central nervous system function.

Single neurons in the thalamus and subthalamic nucleus process cardiac and respiratory signals in humans

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

On the functions of astrocyte-mediated neuronal slow inward currents.

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extrasynaptic N-methyl-D-aspartate receptors with the contribution of astrocytes. These events are significantly slower than the excitatory postsynaptic currents. Parameters of slow inward currents are determined by several factors including the mechanisms of astrocytic activation and glutamate release, as well as the diffusion pathways from the release site towards the extrasynaptic receptors. Astrocytes are stimulated by neuronal network activity, which in turn excite neurons, forming an astrocyte-neuron feedback loop. Mostly as a consequence of brain edema, astrocytic swelling can also induce slow inward currents under pathological conditions. There is a growing body of evidence on the roles of slow inward currents on a single neuron or local network level. These events often occur in synchrony on neurons located in the same astrocytic domain. Besides synchronization of neuronal excitability, slow inward currents also set synaptic strength via eliciting timing-dependent synaptic plasticity. In addition, slow inward currents are also subject to non-synaptic plasticity triggered by long-lasting stimulation of the excitatory inputs. Of note, there might be important region-specific differences in the roles and actions triggering slow inward currents. In greater networks, the pathophysiological roles of slow inward currents can be better understood than physiological ones. Slow inward currents are identified in the pathophysiological background of autism, as slow inward currents drive early hypersynchrony of the neural networks. Slow inward currents are significant contributors to paroxysmal depolarizational shifts/interictal spikes. These events are related to epilepsy, but also found in Alzheimer's disease, Parkinson's disease, and stroke, leading to the decline of cognitive functions. Events with features overlapping with slow inward currents (excitatory, N-methyl-D-aspartate-receptor mediated currents with astrocytic contribution) as ischemic currents and spreading depolarization also have a well-known pathophysiological role in worsening consequences of stroke, traumatic brain injury, or epilepsy. One might assume that slow inward currents occurring with low frequency under physiological conditions might contribute to synaptic plasticity and memory formation. However, to state this, more experimental evidence from greater neuronal networks or the level of the individual is needed. In this review, I aimed to summarize findings on slow inward currents and to speculate on the potential functions of it.

High-throughput mapping of single-neuron projection and molecular features by retrograde barcoded labeling.

Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding brain function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron connectivity patterns, but with limited throughput. Barcode-based connectomics maps large numbers of single-neuron projections, but remains a challenge for jointly analyzing single-cell transcriptomics. Here, we established a rAAV2-retro barcode-based multiplexed tracing method that simultaneously characterizes the projectome and transcriptome at the single neuron level. We uncovered dedicated and collateral projection patterns of ventromedial prefrontal cortex (vmPFC) neurons to five downstream targets and found that projection-defined vmPFC neurons are molecularly heterogeneous. We identified transcriptional signatures of projection-specific vmPFC neurons, and verified Pou3f1 as a marker gene enriched in neurons projecting to the lateral hypothalamus, denoting a distinct subset with collateral projections to both dorsomedial striatum and lateral hypothalamus. In summary, we have developed a new multiplexed technique whose paired connectome and gene expression data can help reveal organizational principles that form neural circuits and process information.

The Interactions of Temporal and Sensory Representations in the Basal Ganglia.

In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a paramount role. Diverse evidence ranging from individual neurons to population activity has demonstrated that this area hosts temporal-related neural representations that may be instrumental for the perception and production of time intervals. However, little is known about how temporal representations interact with other well-known striatal representations, such as kinematic parameters of movements or somatosensory representations. An attractive hypothesis suggests that somatosensory representations may serve as the scaffold for complex representations such as elapsed time. Alternatively, these representations may coexist as independent streams of information that could be integrated into downstream nuclei, such as the substantia nigra or the globus pallidus. In this review, we will revise the available information suggesting an instrumental role of sensory representations in the construction of temporal representations at population and single-neuron levels throughout the basal ganglia.

Single-neuron analysis of axon arbors reveals distinct presynaptic organizations between feedforward and feedback projections

The morphology and spatial distribution of axon arbors and boutons are crucial for neuron presynaptic functions. However, the principles governing their whole-brain organization at the single-neuron level remain unclear. We developed a machine-learning method to separate axon arbors from passing axons in single-neuron reconstruction from fluorescence micro-optical sectioning tomography imaging data and obtained 62,374 axon arbors that displayed distinct morphology, spatial patterns, and scaling laws dependent on neuron types and targeted brain areas. Focusing on the axon arbors in the thalamus and cortex, we revealed the segregated spatial distributions and distinct morphology but shared topographic gradients between feedforward and feedback projections. Furthermore, we uncovered an association between arbor complexity and microglia density. Finally, we found that the boutons on terminal arbors show branch-specific clustering with a log-normal distribution that again differed between feedforward and feedback terminal arbors. Together, our study revealed distinct presynaptic structural organizations underlying diverse functional innervation of single projection neurons.

A paradigm for ethanol consumption in head-fixed mice during prefrontal cortical two-photon calcium imaging

The prefrontal cortex (PFC) is a hub for cognitive behaviors and is a key target for neuroadaptations in alcohol use disorders. Recent advances in genetically encoded sensors and functional microscopy allow multimodal in vivo PFC activity recordings at subcellular and cellular scales. While these methods could enable a deeper understanding of the relationship between alcohol and PFC function/dysfunction, they typically require animals to be head-fixed. Here, we present a method in mice for binge-like ethanol consumption during head-fixation. Male and female mice were first acclimated to ethanol by providing home cage access to 20% ethanol (v/v) for 4 or 8 days. After home cage drinking, mice consumed ethanol from a lick spout during head-fixation. We used two-photon calcium imaging during the head-fixed drinking paradigm to record from a large population of PFC neurons (>1000) to explore how acute ethanol affects their activity. Drinking exerted temporally heterogeneous effects on PFC activity at single neuron and population levels. Intoxication modulated the tonic activity of some neurons while others showed phasic responses around ethanol receipt. Population level activity did not show tonic or phasic modulation but tracked ethanol consumption over the minute-timescale. Network level interactions assessed through between-neuron pairwise correlations were largely resilient to intoxication at the population level while neurons with increased tonic activity showed higher synchrony by the end of the drinking period. By establishing a method for binge-like drinking in head-fixed mice, we lay the groundwork for leveraging advanced microscopy technologies to study alcohol-induced neuroadaptations in PFC and other brain circuits.This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

Outcome of stereo-electroencephalography with single-unit recording in drug-refractory epilepsy.

The aim of this study was to evaluate the utility and safety of "hybrid" stereo-electroencephalography (SEEG) in guiding epilepsy surgery and in providing information at single-neuron levels (i.e., single-unit recording) to further the understanding of the mechanisms of epilepsy and the neurocognitive processes unique to humans. The authors evaluated 218 consecutive patients undergoing SEEG procedures from 1993 through 2018 at a single academic medical center to assess the utility and safety of this technique in both guiding epilepsy surgery and providing single-unit recordings. The hybrid electrodes used in this study contained macrocontacts and microwires to simultaneously record intracranial EEG and single-unit activity (hybrid SEEG). The outcomes of SEEG-guided surgical interventions were examined, as well as the yield and scientific utility of single-unit recordings in 213 patients who participated in the research involving single-unit recordings. All patients underwent SEEG implantation by a single surgeon and subsequent video-EEG monitoring (mean of 10.2 electrodes per patient and 12.0 monitored days). Epilepsy networks were localized in 191 (87.6%) patients. Two clinically significant procedural complications (one hemorrhage and one infection) were noted. Of 130 patients who underwent subsequent focal epilepsy surgery with a minimum 12-month follow-up, 102 (78.5%) underwent resective surgery and 28 (21.5%) underwent closed-loop responsive neurostimulation (RNS) with or without resection. Seizure freedom was achieved in 65 (63.7%) patients in the resective group. In the RNS group, 21 (75.0%) patients achieved 50% or greater seizure reduction. When the initial period of 1993 through 2013 before responsive neurostimulator implantation in 2014 was compared with the subsequent period of 2014 through 2018, the proportion of SEEG patients undergoing focal epilepsy surgery grew from 57.9% to 79.7% due to the advent of RNS, despite a decline in focal resective surgery from 55.3% to 35.6%. A total of 18,680 microwires were implanted in 213 patients, resulting in numerous significant scientific findings. Recent recordings from 35 patients showed a yield of 1813 neurons, with a mean yield of 51.8 neurons per patient. Hybrid SEEG enables safe and effective localization of epileptogenic zones to guide epilepsy surgery and provides unique scientific opportunities to investigate neurons from various brain regions in conscious patients. This technique will be increasingly utilized due to the advent of RNS and may prove a useful approach to probe neuronal networks in other brain disorders.

Configuration-sensitive face-body interactions in primate visual cortex

Traditionally, the neural processing of faces and bodies is studied separately, although they are encountered together, as parts of an agent. Despite its social importance, it is poorly understood how faces and bodies interact, particularly at the single-neuron level. Here, we examined the interaction between faces and bodies in the macaque inferior temporal (IT) cortex, targeting an fMRI-defined patch. We recorded responses of neurons to monkey images in which the face was in its natural location (natural face-body configuration), or in which the face was mislocated with respect to the upper body (unnatural face-body configuration). On average, the neurons did not respond stronger to the natural face-body configurations compared to the summed responses to their faces and bodies, presented in isolation. However, the neurons responded stronger to the natural compared to the unnatural face-body configurations. This configuration effect was present for face- and monkey-centered images, did not depend on local feature differences between configurations, and was present when the face was replaced by a small object. The face-body interaction rules differed between natural and unnatural configurations. In sum, we show for the first time that single IT neurons process faces and bodies in a configuration-specific manner, preferring natural face-body configurations.

Stochastic resonance in sparse neuronal network: functional role of ongoing activity to detect weak sensory input in awake auditory cortex of rat.

The awake cortex is characterized by a higher level of ongoing spontaneous activity, but it has a better detectability of weak sensory inputs than the anesthetized cortex. However, the computational mechanism underlying this paradoxical nature of awake neuronal activity remains to be elucidated. Here, we propose a hypothetical stochastic resonance, which improves the signal-to-noise ratio (SNR) of weak sensory inputs through nonlinear relations between ongoing spontaneous activities and sensory-evoked activities. Prestimulus and tone-evoked activities were investigated via in vivo extracellular recording with a dense microelectrode array covering the entire auditory cortex in rats in both awake and anesthetized states. We found that tone-evoked activities increased supralinearly with the prestimulus activity level in the awake state and that the SNR of weak stimulus representation was optimized at an intermediate level of prestimulus ongoing activity. Furthermore, the temporally intermittent firing pattern, but not the trial-by-trial reliability or the fluctuation of local field potential, was identified as a relevant factor for SNR improvement. Since ongoing activity differs among neurons, hypothetical stochastic resonance or "sparse network stochastic resonance" might offer beneficial SNR improvement at the single-neuron level, which is compatible with the sparse representation in the sensory cortex.

A Miniature Ultrasound Source for Neural Modulation.

This work describes a unique ultrasound (US) exposure system designed to create very localized ( [Formula: see text]) sound fields at operating frequencies that are currently being used for preclinical US neuromodulation. This system can expose small clusters of neuronal tissue, such as cell cultures or intact brain structures in target animal models, opening up opportunities to examine possible mechanisms of action. We modified a dental descaler and drove it at a resonance frequency of 96 kHz, well above its nominal operating point of 28 kHz. A ceramic microtip from an ultrasonic wire bonder was attached to the end of the applicator, creating a 100- [Formula: see text] point source. The device was calibrated with a polyvinylidene difluoride (PVDF) membrane hydrophone, in a novel, air-backed, configuration. The experimental results were confirmed by simulation using a monopole model. The results show a consistent decaying sound field from the tip, well-suited to neural stimulation. The system was tested on an existing neurological model, Drosophila melanogaster, which has not previously been used for US neuromodulation experiments. The results show brain-directed US stimulation induces or suppresses motor actions, demonstrated through synchronized tracking of fly limb movements. These results provide the basis for ongoing and future studies of US interaction with neuronal tissue, both at the level of single neurons and intact organisms.

Neural mechanisms for spatial cognition across vertebrates

The ability to navigate the world is a critical cognitive skill that most animals use to find food, shelter, and mates. Understanding the neural basis of navigation requires probing how the brain encodes spatial information through the study of the activity of single neurons and neuronal populations. Classically in vertebrates, studies have centered on the rodent hippocampal formation, which led to the discovery of place, grid, head direction and other cell types. However, since navigation skills are essential to almost all vertebrates, spatial cognition in different species also needs to be explored. In recent years, as a result of advances in technology, new data have emerged on the ways in which space is represented during navigation in the brains of vertebrates other than rodents, including teleost fish, birds, and other mammal species. Here, we review the state of the art on the neural representation of an animal’s position and motion across vertebrates at the level of single neurons. We argue that it is time to pool information across vertebrates to identify the underlying algorithms that lead to successful navigation. Although rodent-based data are important, findings in rodents are unlikely to cover the full spectrum of neural computations supporting navigation strategies in the vertebrate kingdom. Studying other species can shed light on length scales such as in large environments, and different scenarios such as naturalistic environments that are hard to carry out in rodents. In addition, a rodent-centric view may neglect the fact that different species are likely to represent positions in the world in ways that do not exist in mammals. Finally, we provide an outlook for the future which includes prediction about findings in unexplored species, and the opportunities for discoveries and understanding in this field.

A prefrontal cortex alpha/delta switch controls the transition from positive to negative affective states

Positive and negative emotional states in rats can be studied by investigating ultrasonic vocalizations (USVs). Positive affect in rats is indexed by 50 kHz hedonic USVs, and negative affect is indexed by 22 kHz aversive calls. We examined the relationship of emotional states in rats using medial prefrontal cortex (MPFC) quantitative electroencephalograms (qEEG) and found that hedonic USVs were associated with active wake qEEG (high alpha/low delta power), and aversive USVs occurred with groggy wake qEEG (low alpha/high delta). Further, alpha frequency electrical stimulation of the MPFC induces hedonic calls and reward-seeking behavior, whereas delta frequency stimulation produces aversive calls and avoidance behavior. The brain region responsible for generating motor output for USVs, the periaqueductal gray (PAG), shows a motor-evoked potential that is temporally locked to the alpha (hedonic) and delta (aversive) motor-evoked potential. Closed-loop alpha frequency electrical stimulation could prevent delta qEEG and aversive USVs. At the neuronal circuit level, the alpha rhythm was associated with synaptic long-term potentiation (LTP) in the cortex, whereas the delta rhythm was associated with synaptic depotentiation (LTD) in the cortex. At the pharmacological level, NMDAR and growth factor modulation regulated these forms of neuroplasticity. At the single neuron level, excitatory neurons show increased activity in response to alpha frequencies and decreased activity during delta frequencies. In humans, the feeling of joy increased alpha and decreased delta power in frontal scalp qEEG, and the opposite response was seen for sadness. Thus, the synchronization of alpha/delta oscillations through the neuronal circuit responsible for emotional expression coordinates emotional behavior, and the switch between active wake/positive affect and groggy wake/negative affect is under the control of an LTP- LTD synaptic plasticity mechanism.

Neuronal Encoding of Speech Features in the Human Thalamus in Parkinson's Disease and Essential Tremor Patients.

The human thalamus is known, from stimulation studies and functional imaging, to participate in high-level language tasks. The goal of this study is to find whether and how speech features, in particular, vowel phonemes, are encoded in the neuronal activity of the thalamus, and specifically of the left ventralis intermediate nucleus (Vim), during speech production, perception, and imagery. In this cross-sectional study, we intraoperatively recorded single neuron activity in the left Vim of eight neurosurgical patients with Parkinson's disease (PD) (n = 4) or essential tremor (n = 4) undergoing implantation of deep brain stimulation (n = 3) or radiofrequency lesioning (n = 5) while patients articulated the five monophthongal vowel sounds. In this article, we report that single neurons in the left Vim encode individual vowel phonemes mainly during speech production but also during perception and imagery. They mainly use one of two encoding schemes: broad or sharp tuning, with a similar percentage of units each. Sinusoidal tuning has been demonstrated in almost half of the broadly tuned units. Patients with PD had a lower percentage of speech-related units in each aspect of speech (production, perception, and imagery), a significantly lower percentage of broadly tuned units, and significantly lower median firing rates during speech production and perception, but significantly higher rates during imagery, than patients with essential tremor. The results suggest that the left Vim uses mixed encoding schemes for speech features. Our findings explain, at the single neuron level, why deep brain stimulation and radiofrequency lesioning of the left Vim are likely to cause speech side effects. Moreover, they may indicate that speech-related units in the left Vim of patients with PD may be degraded even in the subclinical phase.

Distractor-Specific Single Neuron Activity Predicts Visual Working Memory Task Outcomes


 
 
 
 This paper explores the relationship between neural activity and behavioral performance in the form of visual working memory (VWM) task outcomes, by answering the question: Are there any significant differences in the firing rates of individual neurons during the distractor presentation period of a VWM task between success and error trials that can predict the outcome of a trial? Distractor-specific single neuron firing rates during a VWM task were analyzed to answer this question. A logistic regression was used to identify the predictive capability of neural firing rate on trial outcome with the neural activity of 51 cells from the lateral prefrontal cortex (LPFC) of a primate. This study found that a best-fit logistic model could predict the behavioral performance of the primate (success or error of the VWM task) with 63.01% accuracy, with additional machine learning techniques producing scores upwards of 68% accuracy. Moreover, greater firing rates in response to the distractor, indicating less efficient distractor suppression, accompanied the error trials of the VWM task. This suggests that stronger neural responses to task-specific distractors can hinder the attentional filtering required for efficient working memory, supporting previous research that found that distractor suppression is a mechanism that heavily influences WM efficiency. These findings indicate that people, particularly children, with disorders that affect WM capacity such as ADHD may experience stronger neural responses to distractors, and therefore inefficient distractor suppression, at the single neuron level when engaging in goal-oriented behaviors, which can significantly impact learning and other developmental processes.
 
 
 

Sequence anticipation and spike-timing-dependent plasticity emerge from a predictive learning rule

Intelligent behavior depends on the brain’s ability to anticipate future events. However, the learning rules that enable neurons to predict and fire ahead of sensory inputs remain largely unknown. We propose a plasticity rule based on predictive processing, where the neuron learns a low-rank model of the synaptic input dynamics in its membrane potential. Neurons thereby amplify those synapses that maximally predict other synaptic inputs based on their temporal relations, which provide a solution to an optimization problem that can be implemented at the single-neuron level using only local information. Consequently, neurons learn sequences over long timescales and shift their spikes towards the first inputs in a sequence. We show that this mechanism can explain the development of anticipatory signalling and recall in a recurrent network. Furthermore, we demonstrate that the learning rule gives rise to several experimentally observed STDP (spike-timing-dependent plasticity) mechanisms. These findings suggest prediction as a guiding principle to orchestrate learning and synaptic plasticity in single neurons.

Serotonin increases population coding of behaviorally relevant stimuli by enhancing responses of ON but not OFF-type sensory neurons

How neural populations encode sensory input to generate behavioral responses remains a central problem in systems neuroscience. Here we investigated how neuromodulation influences population coding of behaviorally relevant stimuli to give rise to behavior in the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. We performed multi-unit recordings from ON and OFF sensory pyramidal cells in response to stimuli whose amplitude (i.e., envelope) varied in time, before and after electrical stimulation of the raphe nuclei. Overall, raphe stimulation increased population coding by ON- but not by OFF-type cells, despite both cell types showing similar sensitivities to the stimulus at the single neuron level. Surprisingly, only changes in population coding by ON-type cells were correlated with changes in behavioral responses. Taken together, our results show that neuromodulation differentially affects ON vs. OFF-type cells in order to enhance perception of behaviorally relevant sensory input.