Responses In Sensory Cortex Research Articles

On the contrast response function of adapted neural populations.

The magnitude of neural responses in sensory cortex depends on the intensity of a stimulus and its probability of being observed within the environment. How these two variables combine to influence the overall response of cortical populations remains unknown. Here we show that, in primary visual cortex, the vector magnitude of the population response is described by a separable power law that factors the intensity of a stimulus and its probability. Moreover, the discriminability between two contrast levels in a cortical population is proportional to the logarithm of the contrast ratio.NEW & NOTEWORTHY The magnitude of neural responses in sensory cortex depends on the intensity of a stimulus and its probability of being observed within the environment. The authors show that, in primary visual cortex, the vector magnitude of the population response is described by a separable power law that factors the intensity of a stimulus and its probability.

Dynamic amplitude modulation of microstimulation evokes biomimetic onset and offset transients and reduces depression of evoked calcium responses in sensory cortices

BackgroundIntracortical microstimulation (ICMS) is an emerging approach to restore sensation to people with neurological injury or disease. Biomimetic microstimulation, or stimulus trains that mimic neural activity in the brain through encoding of onset and offset transients, could improve the utility of ICMS for brain-computer interface (BCI) applications, but how biomimetic microstimulation affects neural activation is not understood. Current “biomimetic” ICMS trains aim to reproduce the strong onset and offset transients evoked in the brain by sensory input through dynamic modulation of stimulus parameters. Stimulus induced depression of neural activity (decreases in evoked intensity over time) is also a potential barrier to clinical implementation of sensory feedback, and dynamic microstimulation may reduce this effect. ObjectiveWe evaluated how bio-inspired ICMS trains with dynamic modulation of amplitude and/or frequency change the calcium response, spatial distribution, and depression of neurons in the somatosensory and visual cortices. MethodsCalcium responses of neurons were measured in Layer 2/3 of visual and somatosensory cortices of anesthetized GCaMP6s mice in response to ICMS trains with fixed amplitude and frequency (Fixed) and three dynamic ICMS trains that increased the stimulation intensity during the onset and offset of stimulation by modulating the amplitude (DynAmp), frequency (DynFreq), or amplitude and frequency (DynBoth). ICMS was provided for either 1-s with 4-s breaks (Short) or for 30-s with 15-s breaks (Long). ResultsDynAmp and DynBoth trains evoked distinct onset and offset transients in recruited neural populations, while DynFreq trains evoked population activity similar to Fixed trains. Individual neurons had heterogeneous responses primarily based on how quickly they depressed to ICMS, where neurons farther from the electrode depressed faster and a small subpopulation (1–5%) were modulated by DynFreq trains. Neurons that depressed to Short trains were also more likely to depress to Long trains, but Long trains induced more depression overall due to the increased stimulation length. Increasing the amplitude during the hold phase resulted in an increase in recruitment and intensity which resulted in more depression and reduced offset responses. Dynamic amplitude modulation reduced stimulation induced depression by 14.6 ± 0.3% for Short and 36.1 ± 0.6% for Long trains. Ideal observers were 0.031 ± 0.009 s faster for onset detection and 1.33 ± 0.21 s faster for offset detection with dynamic amplitude encoding. ConclusionsDynamic amplitude modulation evokes distinct onset and offset transients, reduces depression of neural calcium activity, and decreases total charge injection for sensory feedback in BCIs by lowering recruitment of neurons during long maintained periods of ICMS. In contrast, dynamic frequency modulation evokes distinct onset and offset transients in a small subpopulation of neurons but also reduces depression in recruited neurons by reducing the rate of activation.

Anesthetic Effects of Sevoflurane on the Mouse Somatosensory Cortex: A Flavoprotein Fluorescence Imaging Study

Objective: Sevoflurane, a volatile inhaled anesthetic, is used clinically for general anesthesia in humans. However, the mechanism of action of sevoflurane is not fully understood. We used transcranial flavoprotein fluorescence imaging to visualize somatic sensory cortex responses to noxious stimuli in mice without and with sevoflurane inhalation anesthesia at different concentrations to investigate sevoflurane effects in mice. Methods: A bipolar stimulating electrode was inserted into the left buccal region of the mouse, and changes in flavoprotein fluorescence intensity in the right somatic sensory cortex were recorded before and after electrical stimulation. Measurements were taken while the mouse was awake, at four levels of sevoflurane concentration (0.5%, 1.0%, 1.5%, and 2.0%; 5 min each), and at 10, 20, and 30 min after the end of sevoflurane inhalation. Results: During the awake period, flavoprotein fluorescence intensities in the right sensory cortex decreased after the onset of electrical stimulation, but after 0.9 s, the fluorescence intensity began to increase, reaching a peak value at 2.1 s. This biphasic response significantly decreased at 0.5% sevoflurane and completely disappeared at sevoflurane concentrations above 1.5%, and restored 10 min after cessation of the sevoflurane inhalation. Furthermore, low concentrations of sevoflurane had little effect on the reduction of receptive fields or the conduction of excitation. Conclusion: We conclude that low concentrations of sevoflurane have little effect on the reduction of receptive fields or the conduction of excitation, and that sevoflurane concentrations above 1.5% completely abolish the sensory cortex response elicited by noxious stimulation.

Juvenile depletion of microglia reduces orientation but not high spatial frequency selectivity in mouse V1

Microglia contain multiple mechanisms that shape the synaptic landscape during postnatal development. Whether the synaptic changes mediated by microglia reflect the developmental refinement of neuronal responses in sensory cortices, however, remains poorly understood. In postnatal life, the development of increased orientation and spatial frequency selectivity of neuronal responses in primary visual cortex (V1) supports the emergence of high visual acuity. Here, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to rapidly and durably deplete microglia in mice during the juvenile period in which increased orientation and spatial frequency selectivity emerge. Excitatory and inhibitory tuning properties were measured simultaneously using multi-photon calcium imaging in layer II/III of mouse V1. We found that microglia depletion generally increased evoked activity which, in turn, reduced orientation selectivity. Surprisingly, microglia were not required for the emergence of high spatial frequency tuned responses. In addition, microglia depletion did not perturb cortical binocularity, suggesting normal depth processing. Together, our finding that orientation and high spatial frequency selectivity in V1 are differentially supported by microglia reveal that microglia are required normal sensory processing, albeit selectively.

Spontaneous activity competes with externally evoked responses in sensory cortex

The interaction between spontaneous and externally evoked neuronal activity is fundamental for a functional brain. Increasing evidence suggests that bursts of high-power oscillations in the 15- to 30-Hz beta-band represent activation of internally generated events and mask perception of external cues. Yet demonstration of the effect of beta-power modulation on perception in real time is missing, and little is known about the underlying mechanism. Here, we used a closed-loop stimulus-intensity adjustment system based on online burst-occupancy analyses in rats involved in a forepaw vibrotactile detection task. We found that the masking influence of burst occupancy on perception can be counterbalanced in real time by adjusting the vibration amplitude. Offline analysis of firing rates (FRs) and local field potentials across cortical layers and frequency bands confirmed that beta-power in the somatosensory cortex anticorrelated with sensory evoked responses. Mechanistically, bursts in all bands were accompanied by transient synchronization of cell assemblies, but only beta-bursts were followed by a reduction of FR. Our closed loop approach reveals that spontaneous beta-bursts reflect a dynamic state that competes with external stimuli.

Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents.

In the neocortex, neuronal processing of sensory events is significantly influenced by context. For instance, responses in sensory cortices are suppressed to repetitive or redundant stimuli, a phenomenon termed “stimulus-specific adaptation” (SSA). However, in a context in which that same stimulus is novel, or deviates from expectations, neuronal responses are augmented. This augmentation is termed “deviance detection” (DD). This contextual modulation of neural responses is fundamental for how the brain efficiently processes the sensory world to guide immediate and future behaviors. Notably, context modulation is deficient in some neuropsychiatric disorders such as schizophrenia (SZ), as quantified by reduced “mismatch negativity” (MMN), an electroencephalography waveform reflecting a combination of SSA and DD in sensory cortex. Although the role of NMDA-receptor function and other neuromodulatory systems on MMN is established, the precise microcircuit mechanisms of MMN and its underlying components, SSA and DD, remain unknown. When coupled with animal models, the development of powerful precision neurotechnologies over the past decade carries significant promise for making new progress into understanding the neurobiology of MMN with previously unreachable spatial resolution. Currently, rodent models represent the best tool for mechanistic study due to the vast genetic tools available. While quantifying human-like MMN waveforms in rodents is not straightforward, the “oddball” paradigms used to study it in humans and its underlying subcomponents (SSA/DD) are highly translatable across species. Here we summarize efforts published so far, with a focus on cortically measured SSA and DD in animals to maintain relevance to the classically measured MMN, which has cortical origins. While mechanistic studies that measure and contrast both components are sparse, we synthesize a potential set of microcircuit mechanisms from the existing rodent, primate, and human literature. While MMN and its subcomponents likely reflect several mechanisms across multiple brain regions, understanding fundamental microcircuit mechanisms is an important step to understand MMN as a whole. We hypothesize that SSA reflects adaptations occurring at synapses along the sensory-thalamocortical pathways, while DD depends on both SSA inherited from afferent inputs and resulting disinhibition of non-adapted neurons arising from the distinct physiology and wiring properties of local interneuronal subpopulations and NMDA-receptor function.

Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex.

Nicotine activates nicotinic acetylcholine receptors and improves cognitive and sensory function, in part by its actions in cortical regions. Physiological studies show that nicotine amplifies stimulus‐evoked responses in sensory cortex, potentially contributing to enhancement of sensory processing. However, the role of specific cell types and circuits in the nicotinic modulation of sensory cortex remains unclear. Here, we performed whole‐cell recordings from pyramidal (Pyr) neurons and inhibitory interneurons expressing parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) in mouse auditory cortex, in vitro. Bath application of nicotine strongly depolarized and excited VIP neurons, weakly depolarized Pyr neurons, and had no effect on the membrane potential of SOM or PV neurons. The use of receptor antagonists showed that nicotine's effects on VIP and Pyr neurons were direct and indirect, respectively. Nicotine also enhanced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in Pyr, VIP, and SOM, but not PV, cells. Using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we show that chemogenetic inhibition of VIP neurons prevents nicotine's effects on Pyr neurons. Since VIP cells preferentially contact other inhibitory interneurons, we suggest that nicotine drives VIP cell firing to disinhibit Pyr cell somata, potentially making Pyr cells more responsive to auditory stimuli. In parallel, activation of VIP cells also directly inhibits Pyr neurons, likely altering integration of other synaptic inputs. These cellular and synaptic mechanisms likely contribute to nicotine's beneficial effects on cognitive and sensory function.

Acute Exercise Modulates Feature-selective Responses in Human Cortex.

An organism's current behavioral state influences ongoing brain activity. Nonhuman mammalian and invertebrate brains exhibit large increases in the gain of feature-selective neural responses in sensory cortex during locomotion, suggesting that the visual system becomes more sensitive when actively exploring the environment. This raises the possibility that human vision is also more sensitive during active movement. To investigate this possibility, we used an inverted encoding model technique to estimate feature-selective neural response profiles from EEG data acquired from participants performing an orientation discrimination task. Participants (n = 18) fixated at the center of a flickering (15 Hz) circular grating presented at one of nine different orientations and monitored for a brief shift in orientation that occurred on every trial. Participants completed the task while seated on a stationary exercise bike at rest and during low- and high-intensity cycling. We found evidence for inverted-U effects; such that the peak of the reconstructed feature-selective tuning profiles was highest during low-intensity exercise compared with those estimated during rest and high-intensity exercise. When modeled, these effects were driven by changes in the gain of the tuning curve and in the profile bandwidth during low-intensity exercise relative to rest. Thus, despite profound differences in visual pathways across species, these data show that sensitivity in human visual cortex is also enhanced during locomotive behavior. Our results reveal the nature of exercise-induced gain on feature-selective coding in human sensory cortex and provide valuable evidence linking the neural mechanisms of behavior state across species.

Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR–NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses.

The most sensitive inputs to cutaneous representing regions of primary somatosensory cortex do not change with behavioral training.

Learning a sensory detection task leads to an increased primary sensory cortex response to the detected stimulus, while learning a sensory discrimination task additionally leads to a decreased sensory cortex response to the distractor stimulus. Neural responses are scaled up, and down, in strength, along with concomitant changes in receptive field size. The present work considers neural response properties that are invariant to learning. Data are drawn from two animals that were trained to detect and discriminate spatially separate taps delivered to positions on the skin of their fingers. Each animal was implanted with electrodes positioned in area 3b, and responses were derived on a near daily basis over 84days in animal 1 and 202days in animal 2. Responses to taps delivered in the receptive field were quantitatively measured each day, and receptive fields were audiomanually mapped each day. In the subset of responses that had light cutaneous receptive fields, a preponderance of the days, the most sensitive region of the field was invariant to training. This skin region was present in the receptive field on all, or nearly all, occasions in which the receptive field was mapped, and this region constituted roughly half of the most sensitive region. These results suggest that maintaining the most sensitive inputs as dominant in cortical receptive fields provide a measure of stability that may be transformationally useful for minimizing reconstruction errors and perceptual constancy.

Progesterone Exacerbates Short-Term Effects of Traumatic Brain Injury on Supragranular Responses in Sensory Cortex and Over-Excites Infragranular Responses in the Long Term.

Progesterone (P4) has been suggested as a neuroprotective agent for traumatic brain injury (TBI) because it ameliorates many post-TBI sequelae. We examined the effects of P4 treatment on the short-term (4 days post-TBI) and long-term (8 weeks post-TBI) aftermath on neuronal processing in the rodent sensory cortex of impact acceleration-induced diffuse TBI. We have previously reported that in sensory cortex, diffuse TBI induces a short-term hypoexcitation that is greatest in the supragranular layers and decreases with depth, but a long-term hyperexcitation that is exclusive to the supragranular layers. Now, adult male TBI-treated rats administered P4 showed, in the short term, even greater suppression in neural responses in supragranular layers but a reversal of the TBI-induced suppression in granular and infragranular layers. In long-term TBI there were only inconsistent effects of P4 on the TBI-induced hyperexcitation in supragranular responses but infragranular responses, which were not affected by TBI alone, were elevated by P4 treatment. Intriguingly, the effects in the injured brain were almost identical to P4 effects in the normal brain, as seen in sham control animals treated with P4: in the short term, P4 effects in the normal brain were identical to those exercised in the injured brain and in the long term, P4 effects in the normal brain were rather similar to what was seen in the TBI brain. Overall, these results provide no support for any protective effects of P4 treatment on neuronal encoding in diffuse TBI, and this was reflected in sensorimotor and other behavior tasks also tested here. Additionally, the effects suggest that mechanisms used for P4 effects in the normal brain are also intact in the injured brain.

Locomotion Controls Spatial Integration in Mouse Visual Cortex

SummaryGrowing evidence indicates that responses in sensory cortex are modulated by factors beyond direct sensory stimulation [1–8]. In primary visual cortex (V1), for instance, responses increase with locomotion [9, 10]. Here we show that this increase is accompanied by a profound change in spatial integration. We recorded from V1 neurons in head-fixed mice placed on a spherical treadmill. We characterized spatial integration and found that the responses of most neurons were suppressed by large stimuli. As in primates [11, 12], this surround suppression increased with stimulus contrast. These effects were captured by a divisive normalization model [13, 14], where the numerator originates from a central region driving the neuron and the denominator originates from a larger suppressive field. We then studied the effects of locomotion and found that it markedly reduced surround suppression, allowing V1 neurons to integrate over larger regions of visual space. Locomotion had two main effects: it increased spontaneous activity, and it weakened the suppressive signals mediating normalization, relative to the driving signals. We conclude that a fundamental aspect of visual processing, spatial integration, is controlled by an apparently unrelated factor, locomotion. This control might operate through the mechanisms that are in place to deliver surround suppression.

Striatal Prediction Error Modulates Cortical Coupling

Both perceptual inference and motor responses are shaped by learned probabilities. For example, stimulus-induced responses in sensory cortices and preparatory activity in premotor cortex reflect how (un)expected a stimulus is. This is in accordance with predictive coding accounts of brain function, which posit a fundamental role of prediction errors for learning and adaptive behavior. We used functional magnetic resonance imaging and recent advances in computational modeling to investigate how (failures of) learned predictions about visual stimuli influence subsequent motor responses. Healthy volunteers discriminated visual stimuli that were differentially predicted by auditory cues. Critically, the predictive strengths of cues varied over time, requiring subjects to continuously update estimates of stimulus probabilities. This online inference, modeled using a hierarchical Bayesian learner, was reflected behaviorally: speed and accuracy of motor responses increased significantly with predictability of the stimuli. We used nonlinear dynamic causal modeling to demonstrate that striatal prediction errors are used to tune functional coupling in cortical networks during learning. Specifically, the degree of striatal trial-by-trial prediction error activity controls the efficacy of visuomotor connections and thus the influence of surprising stimuli on premotor activity. This finding substantially advances our understanding of striatal function and provides direct empirical evidence for formal learning theories that posit a central role for prediction error-dependent plasticity.

A novel role of dendritic gap junction and mechanisms underlying its interaction with thalamocortical conductance in fast spiking inhibitory neurons

BackgroundLittle is known about the roles of dendritic gap junctions (GJs) of inhibitory interneurons in modulating temporal properties of sensory induced responses in sensory cortices. Electrophysiological dual patch-clamp recording and computational simulation methods were used in combination to examine a novel role of GJs in sensory mediated feed-forward inhibitory responses in barrel cortex layer IV and its underlying mechanisms.ResultsUnder physiological conditions, excitatory post-junctional potentials (EPJPs) interact with thalamocortical (TC) inputs within an unprecedented few milliseconds (i.e. over 200 Hz) to enhance the firing probability and synchrony of coupled fast-spiking (FS) cells. Dendritic GJ coupling allows fourfold increase in synchrony and a significant enhancement in spike transmission efficacy in excitatory spiny stellate cells. The model revealed the following novel mechanisms: 1) rapid capacitive current (Icap) underlies the activation of voltage-gated sodium channels; 2) there was less than 2 milliseconds in which the Icap underlying TC input and EPJP was coupled effectively; 3) cells with dendritic GJs had larger input conductance and smaller membrane response to weaker inputs; 4) synchrony in inhibitory networks by GJ coupling leads to reduced sporadic lateral inhibition and increased TC transmission efficacy.ConclusionDendritic GJs of neocortical inhibitory networks can have very powerful effects in modulating the strength and the temporal properties of sensory induced feed-forward inhibitory and excitatory responses at a very high frequency band (>200 Hz). Rapid capacitive currents are identified as main mechanisms underlying interaction between two transient synaptic conductances.

Functional near-infrared spectroscopy study on primary motor and sensory cortex response to clenching

The purpose of this study was to elucidate the influence of clenching and clenching intensity on oxygenated hemoglobin (OxyHb) levels in regional cerebral blood flow as an indicator of brain activity in the primary motor and sensory cortices. Functional near-infrared spectroscopy (fNIRS) was used to minimize the effect of clenching-associated muscle activity in eight healthy subjects. Subjects were required to clench at 20%, 50% and 80% of maximum clenching force. To minimize the effect of temporal muscle activity on the working side of the jaw, the fNIRS probes were positioned contralaterally, in the left temporal region. Activation of the primary motor and sensory cortices with clenching was noted in all subjects, irrespective of intensity of clenching. A significant increase was observed in OxyHb in the primary motor cortex between at 80% and both 20% and 50% clenching intensity. In the primary sensory cortex, OxyHb showed a significant increase between all levels of clenching intensity. The results suggest that clenching elicits activation of both the primary motor and sensory cortices, and that intensity of clenching influences activation levels in the brain.

Cortical representation of dermatomes: MEG-derived maps after tactile stimulation

Mechanical stimulation of skin receptors is known to evoke cortical responses arising from the somatosensory cortex. Here we present a magnetoencephalographic (MEG) study where dermatomal somatosensory-evoked fields (DSSEFs) were recorded after mechanical stimulation of sacral (S1), lumbar (L3), thoracic (Th7), and cervical (C4) dermatomes in three healthy volunteers. All MEG measurements were repeated in order to test the replicability of the results. DSSEFs were successfully measured and modeled in all three participants. The topography and temporal dynamics of cortical responses derived after stimulation of each dermatome are described. We found that cortical-evoked responses can be reliably recorded using MEG after mechanical stimulation of dermatomes when a sufficiently large skin region within the dermatome is stimulated. Primary sensory cortex response (SI) to each of the four dermatomes was replicable and showed stability over time. The MEG-derived individual maps of activation confirm the somatotopic representation of dermatomes in primary sensory cortex and the utility of MEG recordings in disentangling the interactions between primary and secondary sensory cortex during somatic perception.

Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.

Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.