Learning enhances encoding of time and temporal surprise in primary sensory cortex

Primary sensory cortex has long been believed to play a straightforward role in the initial processing of sensory information. Yet, the superficial layers of cortex overall are sparsely active, even during sensory stimulation; moreover, cortical activity is influenced by other modalities, task context, reward, and behavioral state. Our study demonstrates that reinforcement learning dramatically alters representations among longitudinally imaged neurons in superficial layers of mouse primary somatosensory cortex. Learning an object detection task recruits previously unresponsive neurons, enlarging the neuronal population sensitive to touch and behavioral choice. In contrast, cortical responses decrease upon repeated exposure to unrewarded stimuli. Moreover, training improved population encoding of the passage of time, and unexpected deviations in trial timing elicited even stronger responses than touch did. In conclusion, the superficial layers of sensory cortex exhibit a high degree of learning-dependent plasticity and are strongly modulated by non-sensory but behaviorally-relevant features, such as timing and surprise.

Neural Measures of Pitch Processing in EEG Responses to Running Speech

Linearized encoding models are increasingly employed to model cortical responses to running speech. Recent extensions to subcortical responses suggest clinical perspectives, potentially complementing auditory brainstem responses (ABRs) or frequency-following responses (FFRs) that are current clinical standards. However, while it is well-known that the auditory brainstem responds both to transient amplitude variations and the stimulus periodicity that gives rise to pitch, these features co-vary in running speech. Here, we discuss challenges in disentangling the features that drive the subcortical response to running speech. Cortical and subcortical electroencephalographic (EEG) responses to running speech from 19 normal-hearing listeners (12 female) were analyzed. Using forward regression models, we confirm that responses to the rectified broadband speech signal yield temporal response functions consistent with wave V of the ABR, as shown in previous work. Peak latency and amplitude of the speech-evoked brainstem response were correlated with standard click-evoked ABRs recorded at the vertex electrode (Cz). Similar responses could be obtained using the fundamental frequency (F0) of the speech signal as model predictor. However, simulations indicated that dissociating responses to temporal fine structure at the F0 from broadband amplitude variations is not possible given the high co-variance of the features and the poor signal-to-noise ratio (SNR) of subcortical EEG responses. In cortex, both simulations and data replicated previous findings indicating that envelope tracking on frontal electrodes can be dissociated from responses to slow variations in F0 (relative pitch). Yet, no association between subcortical F0-tracking and cortical responses to relative pitch could be detected. These results indicate that while subcortical speech responses are comparable to click-evoked ABRs, dissociating pitch-related processing in the auditory brainstem may be challenging with natural speech stimuli.

Habituation of Somatosensory Evoked Potentials in Patients with Alzheimer’s Disease and Those with Vascular Dementia

Background and Objectives: The most prevalent dementia are Alzheimer’s disease and vascular dementia. There is evidence that cortical synaptic function may differ in these two conditions. Habituation of cortical responses to repeated stimuli is a well-preserved phenomenon in a normal brain cortex, related to an underlying mechanism of synaptic efficacy regulation. Lack of habituation represents a marker of synaptic dysfunction. The purpose of this study was to assess the habituation of somatosensory evoked potentials (SEPs) in 29 patients affected by mild-to-moderate Alzheimer’s disease (AD-type) or vascular (VD-type) dementia. Materials and Methods: All patients underwent a clinical history interview, neuropsychological evaluation, and neuroimaging examination. SEPs were elicited by electrical stimulation of the right median nerve at the wrist. Six-hundred stimuli were delivered, and cortical responses divided in three blocks of 200. Habituation was calculated by measuring changes of N20 amplitude from block 1 to block 3. SEP variables recorded in patients were compared with those recorded in 15 age- and gender-matched healthy volunteers. Results: SEP recordings showed similar N20 amplitudes in AD-type and VD-type patients in block 1, that were higher than those recorded in controls. N20 amplitude decreased from block 1 to block 3 (habituation) in normal subjects and in VD-type patients, whereas in AD-type patients it remained unchanged (lack of habituation). Conclusions: The findings suggest that neurophysiologic mechanisms of synaptic efficacy that underneath habituation are impaired in patients with AD-type dementia but not in patients with VD-type dementia. SEPs habituation may contribute to early distinction of Alzheimer’s disease vs. vascular dementia.

Spatially distributed computation in cortical circuits

The traditional view of neural computation in the cerebral cortex holds that sensory neurons are specialized, i.e., selective for certain dimensions of sensory stimuli. This view was challenged by evidence of contextual interactions between stimulus dimensions in which a neuron's response to one dimension strongly depends on other dimensions. Here we use methods of mathematical modeling, psychophysics, and electrophysiology to address shortcomings of the traditional view. Using a model of a generic cortical circuit, we begin with the simple demonstration that cortical responses are always distributed among neurons, forming characteristic waveforms, which we call neural waves. When stimulated by patterned stimuli, circuit responses arise by interference of neural waves. Resulting patterns of interference depend on interaction between stimulus dimensions. Comparison of these modeled responses with responses of biological vision makes it clear that the framework of neural wave interference provides a useful alternative to the standard concept of neural computation.

Intracorporeal Cortical Telemetry as a Step to Automatic Closed-Loop EEG-Based CI Fitting: A Proof of Concept

Electrically evoked auditory potentials have been used to predict auditory thresholds in patients with a cochlear implant (CI). However, with exception of electrically evoked compound action potentials (eCAP), conventional extracorporeal EEG recording devices are still needed. Until now, built-in (intracorporeal) back-telemetry options are limited to eCAPs. Intracorporeal recording of auditory responses beyond the cochlea is still lacking. This study describes the feasibility of obtaining longer latency cortical responses by concatenating interleaved short recording time windows used for eCAP recordings. Extracochlear reference electrodes were dedicated to record cortical responses, while intracochlear electrodes were used for stimulation, enabling intracorporeal telemetry (i.e., without an EEG device) to assess higher cortical processing in CI recipients. Simultaneous extra- and intra-corporeal recordings showed that it is feasible to obtain intracorporeal slow vertex potentials with a CI similar to those obtained by conventional extracorporeal EEG recordings. Our data demonstrate a proof of concept of closed-loop intracorporeal auditory cortical response telemetry (ICT) with a cochlear implant device. This research breaks new ground for next generation CI devices to assess higher cortical neural processing based on acute or continuous EEG telemetry to enable individualized automatic and/or adaptive CI fitting with only a CI.

The Effects of Working Memory Load on Auditory Distraction in Adults With Attention Deficit Hyperactivity Disorder

Cognitive control provides us with the ability to inter alia, regulate the locus of attention and ignore environmental distractions in accordance with our goals. Auditory distraction is a frequently cited symptom in adults with attention deficit hyperactivity disorder (aADHD)–yet few task-based fMRI studies have explored whether deficits in cognitive control (associated with the disorder) impedes on the ability to suppress/compensate for exogenously evoked cortical responses to noise in this population. In the current study, we explored the effects of auditory distraction as function of working memory (WM) load. Participants completed two tasks: an auditory target detection (ATD) task in which the goal was to actively detect salient oddball tones amidst a stream of standard tones in noise, and a visual n-back task consisting of 0-, 1-, and 2-back WM conditions whilst concurrently ignoring the same tonal signal from the ATD task. Results indicated that our sample of young aADHD (n = 17), compared to typically developed controls (n = 17), had difficulty attenuating auditory cortical responses to the task-irrelevant sound when WM demands were high (2-back). Heightened auditory activity to task-irrelevant sound was associated with both poorer WM performance and symptomatic inattentiveness. In the ATD task, we observed a significant increase in functional communications between auditory and salience networks in aADHD. Because performance outcomes were on par with controls for this task, we suggest that this increased functional connectivity in aADHD was likely an adaptive mechanism for suboptimal listening conditions. Taken together, our results indicate that aADHD are more susceptible to noise interference when they are engaged in a primary task. The ability to cope with auditory distraction appears to be related to the WM demands of the task and thus the capacity to deploy cognitive control.

Distinct Patterns of P1 and C2 VEP Potentiation and Attenuation in Visual Snow: A Case Report

Visual snow syndrome, characterized by persistent flickering dots throughout the visual field, has been hypothesized to arise from abnormal neuronal responsiveness in visual processing regions. Previous research has reported a lack of typical VEP habituation to repeated stimulus presentation in patients with visual snow. Yet these studies generally used pattern-reversal paradigms, which are suboptimal for measuring cortical responses to the onset of foveal stimulation. Instead, these responses are better indexed by the C2, a pattern-onset VEP peaking 100–120 ms after stimulus onset. In this case study, we analyzed the C2 and its adaptation profile in data previously collected from a single patient with visual snow using a “double-pulse” presentation paradigm. In controls, shorter intervals between stimulus pairs were associated with greater attenuation of the C2 VEP, with recovery from adaptation at longer stimulus onset asynchronies (SOAs). However, the visual snow patient showed the opposite pattern, with reduced C2 amplitude at longer SOAs despite distinct C2 peaks at the shortest SOAs. These results stand in contrast not only to the pattern of C2 VEP attenuation in controls, but also to a lack of adaptation previously reported for the pattern-onset P1 VEP in this patient. Exploratory source localization using equivalent current dipole fitting further suggested that P1 and C2 VEPs in the visual snow patient arose from distinct sources in extrastriate visual cortex. While preliminary, these results support differential patterns of VEP attenuation and potentiation within the same individual, potentially pointing toward multiple mechanisms of abnormal neuronal responsiveness in visual snow syndrome.

Similarities Between Somatosensory Cortical Responses Induced via Natural Touch and Microstimulation in the Ventral Posterior Lateral Thalamus in Macaques

Lost sensations, such as touch, could be restored by microstimulation (MiSt) along the sensory neural substrate. Such neuroprosthetic sensory information can be used as feedback from an invasive brain-machine interface (BMI) to control a robotic arm/hand, such that tactile and proprioceptive feedback from the sensorized robotic arm/hand is directly given to the BMI user. Microstimulation in the human somatosensory thalamus (Vc) has been shown to produce somatosensory perceptions. However, until recently, systematic methods for using thalamic stimulation to evoke naturalistic touch perceptions were lacking. We have recently presented rigorous methods for determining a mapping between ventral posterior lateral thalamus (VPL) MiSt, and neural responses in the somatosensory cortex (S1), in a rodent model (Choi et al., 2016; Choi and Francis, 2018). Our technique minimizes the difference between S1 neural responses induced by natural sensory stimuli and those generated via VPL MiSt. Our goal is to develop systems that know what MiSt will produce a given neural response and possibly a more natural "sensation." To date, our optimization has been conducted in the rodent model and simulations. Here we present data from simple non-optimized thalamic MiSt during peri-operative experiments, where we MiSt in the VPL of macaques with a somatosensory system more like humans. We implanted arrays of microelectrodes across the hand area of the macaque S1 cortex as well as in the VPL thalamus. Multi and single-unit recordings were used to compare cortical responses to natural touch and thalamic MiSt in the anesthetized state. Post stimulus time histograms were highly correlated between the VPL MiSt and natural touch modalities, adding support to the use of VPL MiSt towards producing a somatosensory neuroprosthesis in humans.