Behavioral Neuroscience publications

Predation risk induces broad behavioral and physiological responses that have traditionally been considered acute and transitory. However, prolonged or frequent exposure to predators and the sensory cues of their presence they broadcast to the environment impact long-term prey physiology and demographics. Though several studies have assessed acute and chronic stress responses in varied taxa, these attempts have often involved a priori expectations of the molecular pathways involved in physiological responses, such as glucocorticoid pathways and neurohormone production in vertebrates. While relatively little is known about physiological and molecular predator-induced stress in insects, many dramatic insect defensive behaviors have evolved to combat selection by predators. For instance, several moth families, such as Noctuidae, include members equipped with tympanic organs that allow the perception of ultrasonic bat calls and facilitate predation avoidance by eliciting evasive aerial flight maneuvers. In this study, we exposed adult male fall armyworm (Spodoptera frugiperda) moths to recorded ultrasonic bat foraging and attack calls for a prolonged period and constructed a de novo transcriptome based on brain tissue from predator cue-exposed relative to control moths kept in silence. Differential expression analysis revealed that 290 transcripts were highly up- or down-regulated among treatment tissues, with many annotating to noteworthy proteins, including a heat shock protein and an antioxidant enzyme involved in cellular stress. Though nearly 50% of differentially expressed transcripts were unannotated, those that were are implied in a broad range of cellular functions within the insect brain, including neurotransmitter metabolism, ionotropic receptor expression, mitochondrial metabolism, heat shock protein activity, antioxidant enzyme activity, actin cytoskeleton dynamics, chromatin binding, methylation, axonal guidance, cilia development, and several signaling pathways. The five most significantly overrepresented Gene Ontology terms included chromatin binding, macromolecular complex binding, glutamate synthase activity, glutamate metabolic process, and glutamate biosynthetic process. As a first assessment of transcriptional responses to ecologically relevant auditory predator cues in the brain of moth prey, this study lays the foundation for examining the influence of these differentially expressed transcripts on insect behavior, physiology, and life history within the framework of predation risk, as observed in ultrasound-sensitive Lepidoptera and other 'eared' insects.

Daily life often requires the coordination of our actions with those of another partner. After 50 years (1968-2018) of behavioral neurophysiology of motor control, the neural mechanisms that allow such coordination in primates are unknown. We studied this issue by recording cell activity simultaneously from dorsal premotor cortex (PMd) of two male interacting monkeys trained to coordinate their hand forces to achieve a common goal. We found a population of "joint-action cells" that discharged preferentially when monkeys cooperated in the task. This modulation was predictive in nature, because in most cells neural activity led in time the changes of the "own" and of the "other" behavior. These neurons encoded the joint-performance more accurately than "canonical action-related cells", activated by the action per se, regardless of the individual versus interactive context. A decoding of joint-action was obtained by combining the two brains' activities, using cells with directional properties distinguished from those associated to the "solo" behaviors. Action observation-related activity studied when one monkey observed the consequences of the partner's behavior, i.e., the cursor's motion on the screen, did not sharpen the accuracy of joint-action cells' representation, suggesting that it plays no major role in encoding joint-action. When monkeys performed with a non-interactive partner, such as a computer, joint-action cells' representation of the other (non-cooperative) behavior was significantly degraded. These findings provide evidence of how premotor neurons integrate the time-varying representation of the self-action with that of a co-actor, thus offering a neural substrate for successful visuomotor coordination between individuals.SIGNIFICANCE STATEMENT The neural bases of intersubject motor coordination were studied by recording cell activity simultaneously from the frontal cortex of two interacting monkeys, trained to coordinate their hand forces to achieve a common goal. We found a new class of cells, preferentially active when the monkeys cooperated, rather than when the same action was performed individually. These "joint-action neurons" offered a neural representation of joint-behaviors by far more accurate than that provided by the "canonical action-related cells", modulated by the action per se regardless of the individual/interactive context. A neural representation of joint-performance was obtained by combining the activity recorded from the two brains. Our findings offer the first evidence concerning neural mechanisms subtending interactive visuomotor coordination between co-acting agents.

Skill learning is fundamental to the acquisition of many complex behaviors that emerge during development. For example, years of practice give rise to perceptual improvements that contribute to mature speech and language skills. While fully honed learning skills might be thought to offer an advantage during the juvenile period, the ability to learn actually continues to develop through childhood and adolescence, suggesting that the neural mechanisms that support skill learning are slow to mature. To address this issue, we asked whether the rate and magnitude of perceptual learning varies as a function of age as male and female gerbils trained on an auditory task. Adolescents displayed a slower rate of perceptual learning compared with their young and mature counterparts. We recorded auditory cortical neuron activity from a subset of adolescent and adult gerbils as they underwent perceptual training. While training enhanced the sensitivity of most adult units, the sensitivity of many adolescent units remained unchanged, or even declined across training days. Therefore, the average rate of cortical improvement was significantly slower in adolescents compared with adults. Both smaller differences between sound-evoked response magnitudes and greater trial-to-trial response fluctuations contributed to the poorer sensitivity of individual adolescent neurons. Together, these findings suggest that elevated sensory neural variability limits adolescent skill learning. SIGNIFICANCE STATEMENT The ability to learn new skills emerges gradually as children age. This prolonged development, often lasting well into adolescence, suggests that children, teens, and adults may rely on distinct neural strategies to improve their sensory and motor capabilities. Here, we found that practice-based improvement on a sound detection task is slower in adolescent gerbils than in younger or older animals. Neural recordings made during training revealed that practice enhanced the sound sensitivity of adult cortical neurons, but had a weaker effect in adolescents. This latter finding was partially explained by the fact that adolescent neural responses were more variable than in adults. Our results suggest that one mechanistic basis of adult-like skill learning is a reduction in neural response variability.

The integration of direct bottom-up inputs with contextual information is a core feature of neocortical circuits. In area V1, neurons may reduce their firing rates when their receptive field input can be predicted by spatial context. Gamma-synchronized (30–80 Hz) firing may provide a complementary signal to rates, reflecting stronger synchronization between neuronal populations receiving mutually predictable inputs. We show that large uniform surfaces, which have high spatial predictability, strongly suppressed firing yet induced prominent gamma synchronization in macaque V1, particularly when they were colored. Yet, chromatic mismatches between center and surround, breaking predictability, strongly reduced gamma synchronization while increasing firing rates. Differences between responses to different colors, including strong gamma-responses to red, arose from stimulus adaptation to a full-screen background, suggesting prominent differences in adaptation between M- and L-cone signaling pathways. Thus, synchrony signaled whether RF inputs were predicted from spatial context, while firing rates increased when stimuli were unpredicted from context.

Hearing loss has been implicated as a risk factor for schizophrenia, but it is not known whether this association arises from common etiology, top-down influences (e.g., social isolation), bottom-up neurobiological mechanisms, or combinations of these factors. Patients with 22q11.2 Deletion Syndrome (22q11.2DS) have a 25-30% risk of developing schizophrenia, and also suffer frequent hearing loss. Here, we used the Df1 /+ mouse model of 22q11.2DS to investigate the relationship between hearing loss and susceptibility to schizophrenia-relevant brain and behavioral abnormalities. Df1 /+ mice have a multi-gene deletion analogous to the chromosomal microdeletion that causes human 22q11.2DS, and like human 22q11.2DS patients exhibit high rates of hearing loss arising primarily from susceptibility to middle ear inflammation. We found that hearing loss in Df1 /+ mice affected schizophrenia-relevant endophenotypes, including electrophysiological measures of central auditory gain and behavioral measures of auditory sensorimotor gating. Moreover, PV+ inhibitory interneurons, another marker for schizophrenia pathology, were significantly reduced in density in auditory cortex but not secondary motor cortex of Df1 /+ mice with hearing loss. These results reveal bottom-up neurobiological mechanisms through which peripheral hearing loss arising from the 22q11.2 deletion may promote the emergence of schizophrenia-relevant auditory brain and behavioral abnormalities, and also suggest a link between conductive hearing loss and reduced PV+ interneuron density in the auditory cortex. SIGNIFICANCE STATEMENT Hearing loss is a known risk factor for schizophrenia. Deletion of chromosomal locus 22q11.2 is associated with both schizophrenia and hearing loss in humans. In the Df1 /+ mouse model of human 22q11.2 Deletion Syndrome, we find that hearing loss shapes measures that are considered schizophrenia-relevant endophenotypes, such as central auditory gain and auditory sensorimotor gating. Moreover, we report a reduction in density of PV+ inhibitory interneurons in the auditory cortex, but not secondary motor cortex, of Df1 /+ mice with hearing loss. These results suggest mechanisms through which hearing loss associated with the 22q11.2 deletion may promote emergence of schizophrenia-relevant auditory brain and behavioral abnormalities and indicate that conductive hearing loss may influence PV+ interneuron density in the auditory cortex.

Based on anatomical connectivity and basic response characteristics, primate auditory cortex is divided into a central core surrounded by belt and parabelt regions. The encoding of pitch, a prototypical element of sound identity, has been studied in primary auditory cortex (A1) but little is known about how it is encoded and represented beyond A1. The caudal auditory belt and parabelt cortical fields process spatial information but also contain information on non-spatial aspects of sounds. In this study, we examined neuronal responses in these areas to pitch-varied marmoset vocalizations, to derive the consequent representation of pitch in these regions and the potential underlying mechanisms, to compare to the encoding and representation of pitch of the same sounds in A1. With respect to response patterns to the vocalizations, neurons in caudal medial belt (CM) showed similar short-latency and short-duration response patterns to A1, but caudal lateral belt (CL) neurons at the same hierarchical level and caudal parabelt (CPB) neurons at a higher hierarchical level showed delayed or much delayed response onset and prolonged response durations. With respect to encoding of pitch, neurons in all cortical fields showed sensitivity to variations in the vocalization pitch either through modulation of spike-count or of first spike-latency. The utility of the encoding mechanism differed between fields: pitch sensitivity was reliably represented by spike-count variations in A1 and CM, while first spike-latency variation was better for encoding pitch in CL and CPB. In summary, our data show that (a) the traditionally-defined belt area CM is functionally very similar to A1 with respect to the representation and encoding of complex naturalistic sounds, (b) the CL belt area, at the same hierarchical level as CM, and the CPB area, at a higher hierarchical level, have very different response patterns and appear to use different pitch-encoding mechanisms, and (c) caudal auditory fields, proposed to be specialized for encoding spatial location, can also contain robust representations of sound identity.

Midbrain dopamine neurons are thought to play a crucial role in motivating behaviors toward desired goals. While the activity of dopamine single-units is known to adhere closely to the reward prediction error (RPE) signal hypothesized by learning theory, much less is known about the dynamic coordination of population-level neuronal activities in the midbrain. Local field potentials (LFPs) are thought to reflect the changes in membrane potential synchronized across a population of neurons nearby a recording electrode. These changes involve complex combinations of local spiking activity with synaptic processing that are difficult to interpret. Here we sampled LFPs from the substantia nigra pars compacta (SNc) of behaving monkeys to determine if local population-level synchrony encodes specific aspects of a reward/effort instrumental task and whether dopamine single-units participate in that signal. We found that reward-correlated information is encoded in a low-frequency signal (<32-Hz; delta and beta bands) that is synchronized across a neural population that includes dopamine neurons. Conversely, high-frequency power (>33-Hz; gamma band) was anticorrelated with predicted reward value and dopamine single-units were never phase-locked to those frequencies. This high-frequency signal may reflect inhibitory processes that were not otherwise observable. LFP encoding of movement-related parameters was negligible. Together, LFPs provide novel insights into the multidimensional processing of reward information subserved by dopaminergic and other components of the midbrain.

Fifty percent of inner ear disorders are caused by genetic mutations. To develop treatments for genetic inner ear disorders, we designed gene replacement therapies using synthetic adeno-associated viral vectors to deliver the coding sequence for Transmembrane Channel-Like ( Tmc ) 1 or 2 into sensory hair cells of mice with hearing and balance deficits due to mutations in Tmc1 and closely related Tmc2 . Here we report restoration of function in inner and outer hair cells, enhanced hair cell survival, restoration of cochlear and vestibular function, restoration of neural responses in auditory cortex and recovery of behavioral responses to auditory and vestibular stimulation. Secondarily, we find that inner ear Tmc gene therapy restores breeding efficiency, litter survival and normal growth rates in mouse models of genetic inner ear dysfunction. Although challenges remain, the data suggest that Tmc gene therapy may be well suited for further development and perhaps translation to clinical application.

Processing incentive and drive is essential for control of goal-directed behavior. The limbic part of the basal ganglia has been emphasized in these processes, yet the exact neuronal mechanism has remained elusive. In this study, we examined the neuronal activity of the ventral pallidum (VP) and its upstream area, the rostromedial caudate (rmCD), while two male macaque monkeys performed an instrumental lever release task in which a visual cue indicated the forthcoming reward size. We found that the activity of some neurons in VP and rmCD reflected the expected reward size transiently following the cue. Reward size coding appeared earlier and stronger in VP than in rmCD. We also found that the activity in these areas was modulated by the satiation level of monkeys, which also occurred more frequently in VP than in rmCD. The information regarding reward size and satiation level was independently signaled in the neuronal populations of these areas. The data thus highlighted the neuronal coding of key variables for goal-directed behavior in VP. Furthermore, pharmacological inactivation of VP induced more severe deficit of goal-directed behavior than inactivation of rmCD, which was indicated by abnormal error repetition and diminished satiation effect on the performance. These results suggest that VP encodes incentive value and internal drive and plays a pivotal role in the control of motivation to promote goal-directed behavior. SIGNIFICANCE STATEMENT The limbic part of the basal ganglia has been implicated in the motivational control of goal-directed action. Here, we investigated how the ventral pallidum (VP) and the rostromedial caudate (rmCD) encode incentive value and internal drive and control goal-directed behavior. Neuronal recording and subsequent pharmacological inactivation revealed that VP had stronger coding of reward size and satiation level than rmCD. Reward size and satiation level were independently encoded in the neuronal population of these areas. Furthermore, VP inactivation impaired goal-directed behavior more severely than rmCD inactivation. These results highlight the central role of VP in the motivational control of goal-directed action.

How does the human brain rapidly process incoming information in working memory? In growing divergence from a single-region focus on the prefrontal cortex (PFC), recent work argues for emphasis on how distributed neural networks are rapidly coordinated in support of this central neurocognitive function. Previously, we showed that working memory for everyday "what," "where," and "when" associations depends on multiplexed oscillatory systems, in which signals of different frequencies simultaneously link the PFC to parieto-occipital and medial temporal regions, pointing to a complex web of sub-second, bidirectional interactions. Here, we used direct brain recordings to delineate the frontoparietal oscillatory correlates of working memory with high spatiotemporal precision. Seven intracranial patients with electrodes simultaneously localized to prefrontal and parietal cortices performed a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. First, task-induced oscillations in the same delta-theta (2-7 Hz) and alpha-beta (9-24 Hz) frequency ranges previously identified using scalp electroencephalography (EEG) carried information about the contents of working memory. Second, maintenance was linked to directional connectivity from the parietal cortex to the PFC. However, presentation of the test prompt to cue identity, spatial, or temporal information changed delta-theta coordination from a unidirectional, parietal-led system to a bidirectional, frontoparietal system. Third, the processing of spatiotemporal information was more bidirectional in the delta-theta range than was the processing of identity information, where alpha-beta connectivity did not exhibit sensitivity to the contents of working memory. These findings implicate a bidirectional delta-theta mechanism for frontoparietal control over the contents of working memory.

Mesoscale cortical activity can be defined as the organization of activity of large neuron populations into collective action, forming time-dependent patterns such as traveling waves. Although collective action may play an important role in the cross-scale integration of brain activity and in the emergence of cognitive behavior, a comprehensive formulation of the laws governing its dynamics is still lacking. Because collective action processes are macroscopic with respect to neuronal activity, these processes cannot be described directly with methods and models developed for the microscale (individual neurons).To identify the characteristic features of mesoscopic dynamics, and to lay the foundations for a theoretical description of mesoscopic activity in the hippocampus, we conduct a comprehensive examination of observational data of hippocampal local field potential (LFP) recordings. We use the strong correlation between rat running-speed and the LFP power to parameterize the energy input into the hippocampus, and show that both the power and non-linearity of collective action (e.g., theta and gamma rhythms) increase with increased speed. Our results show that collective-action dynamics are stochastic (the precise state of a single neuron is irrelevant), weakly non-linear, and weakly dissipative. These are the principles of the theory of weak turbulence. Therefore, we propose weak turbulence a theoretical framework for the description of mesoscopic activity in the hippocampus. The weak turbulence framework provides a complete description of the cross-scale energy exchange (the energy cascade). It uncovers the mechanism governing major features of LFP spectra and bispectra, such as the physical meaning of the exponent α of power-law LFP spectra (e.g., f -α, where f is the frequency), the strengthening of theta-gamma coupling with energy input into the hippocampus, as well as specific phase lags associated with their interaction. Remarkably, the weak turbulence framework is consistent with the theory of self organized criticality, which provides a simple explanation for the existence of the power-law background spectrum. Together with self-organized criticality, weak turbulence could provide a unifying approach to modeling the dynamics of mesoscopic activity.

Neuronal signals in the prefrontal cortex have been reported to predict upcoming decisions. Such activity patterns are often coupled to perceptual cues indicating correct choices or values of different options. How does the prefrontal cortex signal future decisions when no cues are present but when decisions are made based on internal valuations of past experiences with stochastic outcomes? We trained rats to perform a two-arm bandit-task, successfully adjusting choices between certain-small or possible-big rewards with changing long-term advantages. We discovered specialized prefrontal neurons, whose firing during the encounter of no-reward predicted the subsequent choice of animals, even for unlikely or uncertain decisions and several seconds before choice execution. Optogenetic silencing of the prelimbic cortex exclusively timed to encounters of no reward, provoked animals to excessive gambling for large rewards. Firing of prefrontal neurons during outcome evaluation signals subsequent choices during gambling and is essential for dynamically adjusting decisions based on internal valuations.

Closed-loop neuromodulation systems aim to treat a variety of neurological conditions by delivering and adjusting therapeutic electrical stimulation in response to a patient's neural state, recorded in real time. Existing systems are limited by low channel counts, lack of algorithmic flexibility, and the distortion of recorded signals by large and persistent stimulation artefacts. Here, we describe an artefact-free wireless neuromodulation device that enables research applications requiring high-throughput data streaming, low-latency biosignal processing, and simultaneous sensing and stimulation. The device is a miniaturized neural interface capable of closed-loop recording and stimulation on 128 channels, with on-board processing to fully cancel stimulation artefacts. In addition, it can detect neural biomarkers and automatically adjust stimulation parameters in closed-loop mode. In a behaving non-human primate, the device enabled long-term recordings of local field potentials and the real-time cancellation of stimulation artefacts, as well as closed-loop stimulation to disrupt movement preparatory activity during a delayed-reach task. The neuromodulation device may help advance neuroscientific discovery and preclinical investigations of stimulation-based therapeutic interventions.

Psychophysical methods similar to those employed with bats were used to examine jittered echo-delay resolution in bottlenose dolphins (Tursiops truncatus). Two dolphins were trained to produce echolocation clicks and report a change from electronic echoes with a fixed delay of ~ 12.6 ms (~ 9.4 m simulated range) to echoes with delays that alternated (jittered) between successive emitted signals. Jitter delays varied from 0 to 50 µs. Jittered echo-delay thresholds were between 1 and 2 µs-the lowest achievable (non-zero) values with the hardware configuration. Error functions matched the click autocorrelation function near zero jitter delay, and were well within the envelope of the autocorrelation function; however, measured jitter delay thresholds were larger than predictions for a coherent or semicoherent receiver at comparable signal-to-noise ratios. When one of the two alternating jittered echoes was inverted in polarity, both dolphins reliably discriminated echoes at all jittered echo delays, including 0 µs (i.e., only jittering in polarity, not delay). Finally, both dolphins used unusual patterns of click emissions, where groups of echolocation clicks were interspersed with silent gaps. Further tests with sub-microsecond jitter values and various echo signal-to-noise ratios would be necessary for proper direct comparison with jitter detection values obtained for bats.

Activation of the mesolimbic dopamine system reinforces goal-directed behaviours. With repetitive stimulation-for example, by chronic drug abuse-the reinforcement may become compulsive and intake continues even in the face of major negative consequences. Here we gave mice the opportunity to optogenetically self-stimulate dopaminergic neurons and observed that only a fraction of mice persevered if they had to endure an electric shock. Compulsive lever pressing was associated with an activity peak in the projection terminals from the orbitofrontal cortex (OFC) to the dorsal striatum. Although brief inhibition of OFC neurons temporarily relieved compulsive reinforcement, we found that transmission from the OFC to the striatum was permanently potentiated in persevering mice. To establish causality, we potentiated these synapses in vivo in mice that stopped optogenetic self-stimulation of dopamine neurons because of punishment; this led to compulsive lever pressing, whereas depotentiation in persevering mice had the converse effect. In summary, synaptic potentiation of transmission from the OFC to the dorsal striatum drives compulsive reinforcement, a defining symptom of addiction.

Hearing depends on extracting frequency, intensity, and temporal properties from sound to generate an auditory map for acoustical signal processing. How physiology intersects with molecular specification to fine tune the developing properties of the auditory system that enable these aspects remains unclear. We made a novel conditional deletion model that eliminates the transcription factor NEUROD1 exclusively in the ear. These mice (both sexes) develop a truncated frequency range with no neuroanatomically recognizable mapping of spiral ganglion neurons onto distinct locations in the cochlea nor a cochleotopic map presenting topographically discrete projections to the cochlear nuclei. The disorganized primary cochleotopic map alters tuning properties of the inferior colliculus units, which display abnormal frequency, intensity, and temporal sound coding. At the behavioral level, animals show alterations in the acoustic startle response, consistent with altered neuroanatomical and physiological properties. We demonstrate that absence of the primary afferent topology during embryonic development leads to dysfunctional tonotopy of the auditory system. Such effects have never been investigated in other sensory systems because of the lack of comparable single gene mutation models. SIGNIFICANCE STATEMENT All sensory systems form a topographical map of neuronal projections from peripheral sensory organs to the brain. Neuronal projections in the auditory pathway are cochleotopically organized, providing a tonotopic map of sound frequencies. Primary sensory maps typically arise by molecular cues, requiring physiological refinements. Past work has demonstrated physiologic plasticity in many senses without ever molecularly undoing the specific mapping of an entire primary sensory projection. We genetically manipulated primary auditory neurons to generate a scrambled cochleotopic projection. Eliminating tonotopic representation to auditory nuclei demonstrates the inability of physiological processes to restore a tonotopic presentation of sound in the midbrain. Our data provide the first insights into the limits of physiology-mediated brainstem plasticity during the development of the auditory system.

Figure-ground segregation is the process by which the visual system identifies image elements of figures and segregates them from the background. Previous studies examined figure-ground segregation in the visual cortex of monkeys where figures elicit stronger neuronal responses than backgrounds. It was demonstrated in anesthetized mice that neurons in the primary visual cortex (V1) of mice are sensitive to orientation contrast, but it is unknown whether mice can perceptually segregate figures from a background. Here, we examined figure-ground perception of mice and found that mice can detect figures defined by an orientation that differs from the background while the figure size, position or phase varied. Electrophysiological recordings in V1 of awake mice revealed that the responses elicited by figures were stronger than those elicited by the background and even stronger at the edge between figure and background. A figural response could even be evoked in the absence of a stimulus in the V1 receptive field. Current-source-density analysis suggested that the extra activity was caused by synaptic inputs into layer 2/3. We conclude that the neuronal mechanisms of figure-ground segregation in mice are similar to those in primates, enabling investigation with the powerful techniques for circuit analysis now available in mice.

Tinnitus and hyperacusis are life-disrupting perceptual abnormalities that are often preceded by acoustic overexposure. Animal models of overexposure have suggested a link between these phenomena and neural hyperactivity, i.e., elevated spontaneous rates (SRs) and sound-evoked responses. Prior work has focused on changes in central auditory responses, with less attention paid to the exact nature of the associated cochlear damage. The demonstration that acoustic overexposure can cause cochlear neuropathy without permanent threshold elevation suggests cochlear neuropathy per se may be a key elicitor of neural hyperactivity. We addressed this hypothesis by recording responses in the mouse inferior colliculus (IC) following a bilateral, neuropathic noise exposure. One to three weeks post-exposure, mean SRs were unchanged in mice recorded while awake, or under anesthesia. SRs were also unaffected by more intense, or unilateral exposures. These results suggest that neither neuropathy nor hair cell loss are sufficient to raise SRs in the IC, at least in 7-week-old mice, 1-3 weeks post exposure. However, it is not clear whether our mice had tinnitus. Tone-evoked rate-level functions at the CF were steeper following exposure, specifically in the region of maximal neuropathy. Furthermore, suppression driven by off-CF tones and by ipsilateral noise were reduced. Both changes were especially pronounced in neurons of awake mice. This neural hypersensitivity may manifest as behavioral hypersensitivity to sound - prior work reports that this same exposure causes elevated acoustic startle. Together, these results indicate that neuropathy may initiate a compensatory response in the central auditory system leading to the genesis of hyperacusis.

The selection of behaviorally relevant information from cluttered visual scenes (often referred to as “attention”) is mediated by a cortical large-scale network consisting of areas in occipital, temporal, parietal, and frontal cortex that is organized into a functional hierarchy of feedforward and feedback pathways. In the human brain, little is known about the temporal dynamics of attentional processing from studies at the mesoscopic level of electrocorticography (ECoG), that combines millisecond temporal resolution with precise anatomical localization of recording sites. We analyzed high-frequency broadband responses (HFB) responses from 626 electrodes implanted in 8 epilepsy patients who performed a spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system. HFB responses showed high spatial selectivity and tuning, constituting ECoG response fields (RFs), within and outside the topographic visual system. In accordance with monkey physiology studies, both RF widths and onset latencies increased systematically across the visual processing hierarchy. We used the spatial specificity of HFB responses to quantitatively study spatial attention effects and their temporal dynamics to probe a hierarchical top-down model suggesting that feedback signals back propagate the visual processing hierarchy. Consistent with such a model, the strengths of attentional modulation were found to be greater and modulation latencies to be shorter in posterior parietal cortex, middle temporal cortex and ventral extrastriate cortex compared with early visual cortex. However, inconsistent with such a model, attention effects were weaker and more delayed in anterior parietal and frontal cortex. SIGNIFICANCE STATEMENT In the human brain, visual attention has been predominantly studied using methods with high spatial, but poor temporal resolution such as fMRI, or high temporal, but poor spatial resolution such as EEG/MEG. Here, we investigate temporal dynamics and attention effects across the human visual system at a mesoscopic level that combines precise spatial and temporal measurements by using electrocorticography in epilepsy patients performing a classical spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system, thereby relating them to topography and processing hierarchy. We demonstrate regional differences in temporal dynamics across the attention network. Our findings do not fully support a top-down model that promotes influences on visual cortex by reversing the processing hierarchy.