EEG/ECoG/EMG publications

Animal models of tinnitus are essential for determining the underlying mechanisms and testing pharmacotherapies. However, there is doubt over the validity of current behavioural methods for detecting tinnitus. Here, we applied a stimulus paradigm widely used in a behavioural test (gap-induced inhibition of the acoustic startle reflex GPIAS) whilst recording from the auditory cortex, and showed neural response changes that mirror those found in the behavioural tests. We implanted guinea pigs (GPs) with electrocorticographic (ECoG) arrays and recorded baseline auditory cortical responses to a startling stimulus. When a gap was inserted in otherwise continuous background noise prior to the startling stimulus, there was a clear reduction in the subsequent evoked response (termed gap-induced reductions in evoked potentials; GIREP), suggestive of a neural analogue of the GPIAS test. We then unilaterally exposed guinea pigs to narrowband noise (left ear; 8-10 kHz; 1 h) at one of two different sound levels - either 105 dB SPL or 120 dB SPL - and recorded the same responses seven-to-ten weeks following the noise exposure. Significant deficits in GIREP were observed for all areas of the auditory cortex (AC) in the 120 dB-exposed GPs, but not in the 105 dB-exposed GPs. These deficits could not simply be accounted for by changes in response amplitudes. Furthermore, in the contralateral (right) caudal AC we observed a significant increase in evoked potential amplitudes across narrowband background frequencies in both 105 dB and 120 dB-exposed GPs. Taken in the context of the large body of literature that has used the behavioural test as a demonstration of the presence of tinnitus, these results are suggestive of objective neural correlates of the presence of noise-induced tinnitus and hyperacusis.

Following acute traumatic brain injury (TBI), timely transport to a hospital can significantly improve the prognosis for recovery. There is, however, a dearth of quantitative biomarkers for brain injury that can be rapidly acquired and interpreted in active, field environments in which TBIs are frequently incurred. We explored potential functional indicators for TBI that can be noninvasively obtained through portable detection modalities, namely optical and electrophysiological approaches. By combining diffuse correlation spectroscopy with colocalized electrophysiological measurements in a mouse model of TBI, we observed concomitant alterations in sensory-evoked cerebral blood flow (CBF) and electrical potentials following controlled cortical impact. Injury acutely reduced the peak amplitude of both electrophysiological and CBF responses, which mostly recovered to baseline values within 30 min, and intertrial variability for these parameters was also acutely altered. Notably, the postinjury dynamics of the CBF overshoot and undershoot amplitudes differed significantly; whereas the amplitude of the initial peak of stimulus-evoked CBF recovered relatively rapidly, the ensuing undershoot did not appear to recover within 30 min of injury. Additionally, acute injury induced apparent low-frequency oscillatory behavior in CBF (<1 Hz). Histological assessment indicated that these physiological alterations were not associated with any major, persisting anatomical changes. Several time-domain features of the blood flow and electrophysiological responses showed strong correlations in recovery kinetics. Overall, our results reveal an array of stereotyped, injury-induced alterations in electrophysiological and hemodynamic responses that can be rapidly obtained using a combination of portable detection techniques.

How do humans flexibly respond to changing environmental demands on a sub-second temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behavior, yet the core mechanisms that translate sensory information into behavior remain undefined. Utilizing direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity, indexed by the broadband gamma signal, while sixteen participants performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centered in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behavior.

The auditory brainstem response to a dolphin's own emitted biosonar click can be measured by averaging epochs of the instantaneous electroencephalogram (EEG) that are time-locked to the emitted click. In this study, averaged EEGs were measured using surface electrodes placed on the head in six different configurations while dolphins performed an echolocation task. Simultaneously, biosonar click emissions were measured using contact hydrophones on the melon and a hydrophone in the farfield. The averaged EEGs revealed an electrophysiological potential (the pre-auditory wave, PAW) that preceded the production of each biosonar click. The largest PAW amplitudes occurred with the non-inverting electrode just right of the midline-the apparent side of biosonar click generation-and posterior of the blowhole. Although the source of the PAW is unknown, the temporal and spatial properties rule out an auditory source. The PAW may be a neural or myogenic potential associated with click production; however, it is not known if muscles within the dolphin nasal system can be actuated at the high rates reported for dolphin click production, or if sufficiently coordinated and fast motor endplates of nasal muscles exist to produce a PAW detectable with surface electrodes.

The subthalamic nucleus (STN) is hypothesized to play a central role in the rapid stopping of movement in reaction to a stop signal. Single-unit recording evidence for such a role is sparse, however, and it remains uncertain how that role relates to the disparate functions described for anatomic subdivisions of the STN. Here we address that gap in knowledge using non-human primates and a task that distinguishes reactive and proactive action inhibition, switching and skeletomotor functions. We found that specific subsets of STN neurons have activity consistent with causal roles in reactive action stopping or switching. Importantly, these neurons were strictly segregated to a ventromedial region of STN. Neurons in other subdivisions encoded task dimensions such as movement per se and proactive control. We propose that the involvement of STN in reactive control is restricted to its ventromedial portion, further implicating this STN subdivision in impulse control disorders.

Micro-electrocorticograph (μECoG) arrays offer the flexibility to record local field potentials (LFPs) from the surface of the cortex, using high density electrodes that are sub-mm in diameter. Research to date has not provided conclusive evidence for the underlying signal generation of μECoG recorded LFPs, or if μECoG arrays can capture network activity from the cortex. We studied the pervading view of the LFP signal by exploring the spatial scale at which the LFP can be considered elemental. We investigated the underlying signal generation and ability to capture functional networks by implanting, μECoG arrays to record sensory-evoked potentials in four rats. The organization of the sensory cortex was studied by analyzing the sensory-evoked potentials with two distinct modeling techniques: (1) The volume conduction model, that models the electrode LFPs with an electrostatic representation, generated by a single cortical generator, and (2) the dynamic causal model (DCM), that models the electrode LFPs with a network model, whose activity is generated by multiple interacting cortical sources. The volume conduction approach modeled activity from electrodes separated < 1000 μm, with reasonable accuracy but a network model like DCM was required to accurately capture activity > 1500 μm. The extrinsic network component in DCM was determined to be essential for accurate modeling of observed potentials. These results all point to the presence of a sensory network, and that μECoG arrays are able to capture network activity in the neocortex. The estimated DCM network models the functional organization of the cortex, as signal generators for the μECoG recorded LFPs, and provides hypothesis-testing tools to explore the brain.

Cannabinoids have been suggested as a therapeutic target for a variety of brain disorders. Despite the presence of their receptors throughout the auditory system, little is known about how cannabinoids affect auditory function. We sought to determine whether administration of arachidonyl-2'-chloroethylamide (ACEA), a highly-selective CB1 agonist, could attenuate a variety of auditory effects caused by prior administration of salicylate, and potentially treat tinnitus. We recorded cortical resting-state activity, auditory-evoked cortical activity and auditory brainstem responses (ABRs), from chronically-implanted awake guinea pigs, before and after salicylate + ACEA. Salicylate-induced reductions in click-evoked ABR amplitudes were smaller in the presence of ACEA, suggesting that the ototoxic effects of salicylate were less severe. ACEA also abolished salicylate-induced changes in cortical alpha band (6-10 Hz) oscillatory activity. However, salicylate-induced increases in cortical evoked activity (suggestive of the presence of hyperacusis) were still present with salicylate + ACEA. ACEA administered alone did not induce significant changes in either ABR amplitudes or oscillatory activity, but did increase cortical evoked potentials. Furthermore, in two separate groups of non-implanted animals, we found no evidence that ACEA could reverse behavioural identification of salicylate- or noise-induced tinnitus. Together, these data suggest that while ACEA may be potentially otoprotective, selective CB1 agonists are not effective in diminishing the presence of tinnitus or hyperacusis.

Introduction Resting‐state connectivity patterns have been observed in humans and other mammal species, and can be recorded using a variety of different technologies. Functional connectivity has been previously compared between species using resting‐state fMRI , but not in electrophysiological studies. Methods We compared connectivity with implanted electrodes in humans (electrocorticography) to macaques and sheep (microelectrocorticography), which are capable of recording neural data at high frequencies with spatial precision. We specifically examined synchrony, implicated in functional integration between regions. Results We found that connectivity strength was overwhelmingly similar in humans and monkeys for pairs of two different brain regions (prefrontal, motor, premotor, parietal), but differed more often within single brain regions. The two connectivity measures, correlation and phase locking value, were similar in most comparisons. Connectivity strength agreed more often between the species at higher frequencies. Where the species differed, monkey synchrony was stronger than human in all but one case. In contrast, human and sheep connectivity within somatosensory cortex diverged in almost all frequencies, with human connectivity stronger than sheep. Discussion Our findings imply greater heterogeneity within regions in humans than in monkeys, but comparable functional interactions between regions in the two species. This suggests that monkeys may be effectively used to probe resting‐state connectivity in humans, and that such findings can then be validated in humans. Although the discrepancy between humans and sheep is larger, we suggest that findings from sheep in highly invasive studies may be used to provide guidance for studies in other species.

Oscillatory neural activity in different frequency bands and phase-amplitude coupling (PAC) are hypothesized to be biomarkers of Parkinson’s disease (PD) that could explain dysfunction in the motor circuit and be used for closed-loop deep brain stimulation (DBS). How these putative biomarkers change from the normal to the parkinsonian state across nodes in the motor circuit and within the same subject, however, remains unknown. In this study, we characterized how parkinsonism and vigilance altered oscillatory activity and PAC within the primary motor cortex (M1), subthalamic nucleus (STN), and globus pallidus (GP) in two nonhuman primates. Static and dynamic analyses of local field potential (LFP) recordings indicate that 1) after induction of parkinsonism using the neurotoxin MPTP, low-frequency power (8–30 Hz) increased in the STN and GP in both subjects, but increased in M1 in only one subject; 2) high-frequency power (~330 Hz) was present in the STN in both normal subjects but absent in the parkinsonian condition; 3) elevated PAC measurements emerged in the parkinsonian condition in both animals, but in different sites in each animal (M1 in one subject and GPe in the other); and 4) the state of vigilance significantly impacted how oscillatory activity and PAC were expressed in the motor circuit. These results support the hypothesis that changes in low- and high-frequency oscillatory activity and PAC are features of parkinsonian pathophysiology and provide evidence that closed-loop DBS systems based on these biomarkers may require subject-specific configurations as well as adaptation to changes in vigilance. NEW & NOTEWORTHY Chronically implanted electrodes were used to record neural activity across multiple nodes in the basal ganglia-thalamocortical circuit simultaneously in a nonhuman primate model of Parkinson’s disease, enabling within-subject comparisons of electrophysiological biomarkers between normal and parkinsonian conditions and different vigilance states. This study improves our understanding of the role of oscillatory activity and phase-amplitude coupling in the pathophysiology of Parkinson’s disease and supports the development of more effective DBS therapies based on pathophysiological biomarkers.

Objectives/Hypothesis Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses. Study Design Acute experiments in cats. Methods The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat‐crush injury, and one cat received a transection‐reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement. Results Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments. Conclusions We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury‐model experiments, suggesting a potential role for intraneural MEA implantation in VFP management. Level of Evidence NA. Laryngoscope , 128:1606–1614, 2018

Absence epilepsy is characterized by the occurrence of generalized spike and wave discharges (GSWDs) in electrocorticographical (ECoG) recordings representing oscillatory activity in thalamocortical networks. The oscillatory nature of GSWDs has been shown to be reflected in the simple spike activity of cerebellar Purkinje cells and in the activity of their target neurons in the cerebellar nuclei, but it is unclear to what extent complex spike activity is implicated in generalized epilepsy. Purkinje cell complex spike firing is elicited by climbing fiber activation and reflects action potential firing in the inferior olive. Here, we investigated to what extent modulation of complex spike firing is reflected in the temporal patterns of seizures. Extracellular single-unit recordings in awake, head-restrained homozygous tottering mice, which suffer from a mutation in the voltage-gated CaV2.1 calcium channel, revealed that a substantial proportion of Purkinje cells (26%) showed increased complex spike activity and rhythmicity during GSWDs. Moreover, Purkinje cells, recorded either electrophysiologically or by using Ca2+-imaging, showed a significant increase in complex spike synchronicity for both adjacent and remote Purkinje cells during ictal events. These seizure-related changes in firing frequency, rhythmicity and synchronicity were most prominent in the lateral cerebellum, a region known to receive cerebral input via the inferior olive. These data indicate profound and widespread changes in olivary firing that are most likely induced by seizure-related activity changes in the thalamocortical network, thereby highlighting the possibility that olivary neurons can compensate for pathological brain-state changes by dampening oscillations.

Electrocortical stimulation (ECS) mapping is routinely used to identify critical language sites before resective neurosurgery. The precise locations of these sites are highly variable across patients, occurring in the frontal, temporal, and parietal lobes-it is this variability that necessitates individual patient mapping. But why these particular anatomical sites are so privileged in each patient is unknown. We hypothesized that critical language sites have greater functional connectivity with nearby cortex than sites without critical functions, since they serve as central nodes within the language network. Functional connectivity across language, motor, and cleared sites was measured in 15 patients undergoing electrocortiographic (ECoG) mapping for epilepsy surgery. Critical language sites had significantly higher connectivity than sites without critical functions (P = 0.001), and this also held for motor sites (P = 0.022). These data support the hypothesis that critical language sites are highly connected within the local cortical network, perhaps explaining why their disruption with ECS leads to transient disturbances in language function. It is our hope that improved understanding of the mechanisms of ECS will permit improved surgical planning and perhaps contribute to the understanding of normal language physiology.

Cathodal-transcranial direct current stimulation induces therapeutic effects in animal ischemia models by preventing the expansion of ischemic injury during the hyperacute phase of ischemia. However, its efficacy is limited by an accompanying decrease in cerebral blood flow. On the other hand, peripheral sensory stimulation can increase blood flow to specific brain areas resulting in rescue of neurovascular functions from ischemic damage. Therefore, the two modalities appear to complement each other to form an integrated treatment modality. Our results showed that hemodynamics was improved in a photothrombotic ischemia model, as cerebral blood volume and hemoglobin oxygen saturation (SO2) recovered to 71% and 76% of the baseline values, respectively. Furthermore, neural activities, including somatosensory-evoked potentials (110% increase), the alpha-to-delta ratio (27% increase), and the (delta+theta)/(alpha+beta) ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with a 2-fold preservation in the number of neurons and a 6-fold reduction in the number of active microglia in the infarct region compared with the untreated group. Grip strength was also better preserved (28% higher) compared with the untreated group. Overall, this nonpharmacological, nonintrusive approach could be prospectively developed into a clinical treatment modality.

Background: Our group has previously shown that activation of specific facial nerve (FN) fiber populations and selective activation of facial musculature can be achieved through acute intraneural multichannel microelectrode array (MEA) implantation in the feline model. Hypothesis: Selective stimulation of facial muscles will be maintained in the setting of 1) chronic and 2) acute MEA implantation after FN injury and subsequent recovery. Methods: This study included seven cats. In three cats with normal facial function, 4-channel penetrating MEAs were implanted chronically in the FN and tested biweekly for 6 months. Electrical current pulses were delivered to each channel individually, and elicited electromyographic (EMG) voltage outputs were recorded for each of several facial muscles. For FN injury experiments, two cats received a standardized hemostat-crush injury, and two cats received a transection-reapproximation injury to the FN main trunk. These four underwent acute implantation of MEA and EMG recording in terminal experiments 4 months postinjury. Results: Stimulation through individual channels selectively activated restricted nerve populations, resulting in activation of individual muscles in cats with chronic MEA implantation and after nerve injury. Increasing stimulation current levels resulted in increasing EMG voltage responses in all patients. Nerve histology showed only minor neural tissue reaction to the implant. Conclusion: We have established in the animal model the ability of a chronically implanted MEA to selectively stimulate restricted FN fiber populations and elicit activations in specific facial muscles. Likewise, after FN injury, selective stimulation of restricted FN fiber populations and subsequent activation of discrete facial muscles can be achieved after acute MEA implantation.

Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV+) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations. We found that contextual fear conditioning increased ripple-spindle coupling in mice. However, inhibition of PV+ cells in either CA1 or mPFC eliminated this learning-induced increase in ripple-spindle coupling without affecting ripple or spindle incidence. Consistent with the hypothesized importance of ripple-spindle coupling in memory consolidation, post-training inhibition of PV+ cells disrupted contextual fear memory consolidation. These results indicate that successful memory consolidation requires coherent hippocampal-neocortical communication mediated by PV+ cells.

Cardiac arrest (CA) entails significant risks of coma resulting in poor neurological and behavioral outcomes after resuscitation. Significant subsequent morbidity and mortality in post-CA patients are largely due to the cerebral and cardiac dysfunction that accompanies prolonged whole-body ischemia post-CA syndrome (PCAS). PCAS results in strong inflammatory responses including neuroinflammation response leading to poor outcome. Currently, there are no proven neuroprotective therapies to improve post-CA outcomes apart from therapeutic hypothermia. Furthermore, there are no acceptable approaches to promote cortical or cognitive arousal following successful return of spontaneous circulation (ROSC). Hypothalamic orexinergic pathway is responsible for arousal and it is negatively affected by neuroinflammation. However, whether activation of the orexinergic pathway can curtail neuroinflammation is unknown. We hypothesize that targeting the orexinergic pathway via intranasal orexin-A (ORXA) treatment will enhance arousal from coma and decrease the production of proinflammatory cytokines resulting in improved functional outcome after resuscitation. We used a highly validated CA rat model to determine the effects of intranasal ORXA treatment 30-minute post resuscitation. At 4hrs post-CA, the mRNA levels of proinflammatory markers (IL1β, iNOS, TNF-α, GFAP, CD11b) and orexin receptors (ORX1R and ORX2R) were examined in different brain regions. CA dramatically increased proinflammatory markers in all brain regions particularly in the prefrontal cortex, hippocampus and hypothalamus. Post-CA intranasal ORXA treatment significantly ameliorated the CA-induced neuroinflammatory markers in the hypothalamus. ORXA administration increased production of orexin receptors (ORX1R and ORX2R) particularly in hypothalamus. In addition, ORXA also resulted in early arousal as measured by quantitative electroencephalogram (EEG) markers, and recovery of the associated behavioral neurologic deficit scale score (NDS). Our results indicate that intranasal delivery of ORXA post-CA has an anti-inflammatory effect and accelerates cortical EEG and behavioral recovery. Beneficial outcomes from intranasal ORXA treatment lay the groundwork for therapeutic clinical approach to treating post-CA coma.

Increasing evidence suggests that cortical dynamics during wake exhibits long-range temporal correlations suitable to integrate inputs over extended periods of time to increase the signal-to-noise ratio in decision making and working memory tasks. Accordingly, sleep has been suggested as a state characterized by a breakdown of long-range correlations. However, detailed measurements of neuronal timescales that support this view have so far been lacking. Here, we show that the cortical timescales measured at the individual neuron level in freely behaving male rats change as a function of vigilance state and time awake. Although quiet wake and rapid eye movement (REM) sleep are characterized by similar, long timescales, these long timescales are abrogated in non-REM sleep. We observe that cortex dynamics exhibits rapid transitions between long-timescale states and sleep-like states governed by short timescales even during wake. This becomes particularly evident during sleep deprivation, when the interplay between these states can lead to an increasing disruption of long timescales that are restored after sleep. Experiments and modeling identify the intrusion of neuronal offline periods as a mechanism that disrupts the long timescales arising from reverberating cortical network activity. Our results provide novel mechanistic and functional links among behavioral manifestations of sleep, wake, and sleep deprivation and specific measurable changes in the network dynamics relevant for characterizing the brain's changing information-processing capabilities. They suggest a network-level function of sleep to reorganize cortical networks toward states governed by long timescales to ensure efficient information integration for the time awake. SIGNIFICANCE STATEMENT Lack of sleep deteriorates several key cognitive functions, yet the neuronal underpinnings of these deficits have remained elusive. Cognitive capabilities are generally believed to benefit from a neural circuit's ability to reliably integrate information. Persistent network activity characterized by long timescales may provide the basis for this integration in cortex. Here, we show that long-range temporal correlations indicated by slowly decaying autocorrelation functions in neuronal activity are dependent on vigilance states. Although wake and rapid eye movement (REM) sleep exhibit long timescales, these long-range correlations break down during non-REM sleep. Our findings thus suggest two distinct states in terms of timescale dynamics. During extended wake, the rapid switching to sleep-like states with short timescales can lead to an overall decline in cortical timescales.

The basal forebrain (BF) has long been implicated in attention, learning and memory, and recent studies have established a causal relationship between artificial BF activation and arousal. However, neural ensemble dynamics in the BF still remains unclear. Here, recording neural population activity in the BF and comparing it with simultaneously recorded cortical population under both anesthetized and unanesthetized conditions, we investigate the difference in the structure of spontaneous population activity between the BF and the auditory cortex (AC) in mice. The AC neuronal population show a skewed spike rate distribution, a higher proportion of short (≤80 ms) inter-spike intervals (ISIs) and a rich repertoire of rhythmic firing across frequencies. Although the distribution of spontaneous firing rate in the BF is also skewed, a proportion of short ISIs can be explained by a Poisson model at short time scales (≤20 ms) and spike count correlations are lower compared to AC cells, with optogenetically identified cholinergic cell pairs showing exceptionally higher correlations. Furthermore, a smaller fraction of BF neurons shows spike-field entrainment across frequencies: a subset of BF neurons fire rhythmically at slow (≤6 Hz) frequencies, with varied phase preferences to ongoing field potentials, in contrast to a consistent phase preference of AC populations. Firing of these slow rhythmic BF cells is correlated to a greater degree than other rhythmic BF cell pairs. Overall, the fundamental difference in the structure of population activity between the AC and BF is their temporal coordination, in particular their operational timescales. These results suggest that BF neurons slowly modulate downstream populations whereas cortical circuits transmit signals on multiple timescales. Thus, the characterization of the neural ensemble dynamics in the BF provides further insight into the neural mechanisms, by which brain states are regulated.

The sensitivity of ocular dominance to regulation by monocular deprivation is the canonical model of plasticity confined to a critical period. However, we have previously shown that visual deprivation through dark exposure (DE) reactivates critical period plasticity in adults. Previous work assumed that the elimination of visual input was sufficient to enhance plasticity in the adult mouse visual cortex. In contrast, here we show that light reintroduction (LRx) after DE is responsible for the reactivation of plasticity. LRx triggers degradation of the ECM, which is blocked by pharmacological inhibition or genetic ablation of matrix metalloproteinase-9 (MMP-9). LRx induces an increase in MMP-9 activity that is perisynaptic and enriched at thalamo-cortical synapses. The reactivation of plasticity by LRx is absent in Mmp9−/− mice, and is rescued by hyaluronidase, an enzyme that degrades core ECM components. Thus, the LRx-induced increase in MMP-9 removes constraints on structural and functional plasticity in the mature cortex.

Significance Previous studies demonstrated “auditory looming bias” exclusively by manipulating overall sound intensity. Hence, it is not clear whether this bias truly reflects perceptual differences in sensitivity to motion direction rather than changes in intensity. We manipulated individualized spectral cues to create stimuli that were perceived as either approaching or receding, while controlling loudness. We assessed discrimination of motion direction and analyzed simultaneously recorded neural responses using electroencephalography. Our results show both behavioral and neural evidence of looming bias. Therefore, our study demonstrates that the bias is truly about perceived motion in distance, not intensity changes.