Task Engagement Enhances Population Encoding of Stimulus Meaning in Primary Auditory Cortex

Reliability and Representational Bandwidth in the Auditory Cortex

Functional mapping of cortical areas with optical imaging

Organization of auditory, somatic sensory, and visual projection to association fields of cerebral cortex in the cat.

SUMMARYNeuronal oscillations are suggested to play an important role in auditory working memory (WM), but their contribution to content-specific representations has remained unclear. Here, we measure magnetoencephalography during a retro-cueing task with parametric ripple-sound stimuli, which are spectrotemporally similar to speech but resist non-auditory memory strategies. Using machine learning analyses, with rigorous between-subject cross-validation and non-parametric permutation testing, we show that memorized sound content is strongly represented in phase-synchronization patterns between subregions of auditory and frontoparietal cortices. These phase-synchronization patterns predict the memorized sound content steadily across the studied maintenance period. In addition to connectivity-based representations, there are indices of more local, “activity silent” representations in auditory cortices, where the decoding accuracy of WM content significantly increases after task-irrelevant “impulse stimuli.” Our results demonstrate that synchronization patterns across auditory sensory and association areas orchestrate neuronal coding of auditory WM content. This connectivity-based coding scheme could also extend beyond the auditory domain.

Background:Schizophrenia and bipolar disorder have been linked to alterations in the functional activity and grey matter volume of some brain areas, reflected in impaired regional homogeneity and aberrant voxel-based morphometry. However, because of variable findings and methods used across studies, identifying patterns of brain alteration in schizophrenia and bipolar disorder has been difficult.Methods:We conducted a meta-analysis of differences in regional homogeneity and voxel-based morphometry between patients and healthy controls for schizophrenia and bipolar disorder separately, using seed-based d mapping.Results:We included 45 publications on regional homogeneity (26 in schizophrenia and 19 in bipolar disorder) and 190 publications on voxel-based morphometry (120 in schizophrenia and 70 in bipolar disorder). Patients with schizophrenia showed increased regional homogeneity in the frontal cortex and striatum and the supplementary motor area; they showed decreased regional homogeneity in the insula, primary sensory cortex (visual and auditory cortices) and sensorimotor cortex. Patients with bipolar disorder showed increased regional homogeneity in the frontal cortex and striatum; they showed decreased regional homogeneity in the insula. Patients with schizophrenia showed decreased grey matter volume in the superior temporal gyrus, inferior frontal gyrus, cingulate cortex and cerebellum. Patients with bipolar disorder showed decreased grey matter volume in the insula, cingulate cortex, frontal cortex and thalamus. Overlap analysis showed that patients with schizophrenia displayed decreased regional homogeneity and grey matter volume in the left insula and left superior temporal gyrus; patients with bipolar disorder displayed decreased regional homogeneity and grey matter volume in the left insula.Limitations:The small sample size for our subgroup analysis (unmedicated versus medicated patients and substantial heterogeneity in the results for some regions could limit the interpretability and generalizability of the results.Conclusion:Patients with schizophrenia and bipolar disorder shared a common pattern of regional functional and structural alterations in the insula and frontal cortex. Patients with schizophrenia showed more widespread functional and structural impairment, most prominently in the primary sensory motor areas.

Most mammals rely on the extraction of acoustic information from the environment in order to survive. However, the mechanisms that support sound representation in auditory neural networks involving sensory and association brain areas remain underexplored. In this study, we address the functional connectivity between an auditory region in frontal cortex (the frontal auditory field, FAF) and the auditory cortex (AC) in the bat Carollia perspicillata. The AC is a classic sensory area central for the processing of acoustic information. On the other hand, the FAF belongs to the frontal lobe, a brain region involved in the integration of sensory inputs, modulation of cognitive states, and in the coordination of behavioral outputs. The FAF-AC network was examined in terms of oscillatory coherence (local-field potentials, LFPs), and within an information theoretical framework linking FAF and AC spiking activity. We show that in the absence of acoustic stimulation, simultaneously recorded LFPs from FAF and AC are coherent in low frequencies (1–12 Hz). This “default” coupling was strongest in deep AC layers and was unaltered by acoustic stimulation. However, presenting auditory stimuli did trigger the emergence of coherent auditory-evoked gamma-band activity (>25 Hz) between the FAF and AC. In terms of spiking, our results suggest that FAF and AC engage in distinct coding strategies for representing artificial and natural sounds. Taken together, our findings shed light onto the neuronal coding strategies and functional coupling mechanisms that enable sound representation at the network level in the mammalian brain.

Primary auditory cortex is a critical stage in the human auditory pathway, a gateway between subcortical and higher-level cortical areas. Receiving the output of all subcortical processing, it sends its output on to higher-level cortex. Non-invasive physiological recordings of primary auditory cortex using electroencephalography (EEG) and magnetoencephalography (MEG), however, may not have sufficient specificity to separate responses generated in primary auditory cortex from those generated in underlying subcortical areas or neighboring cortical areas. This limitation is important for investigations of effects of top-down processing (e.g., selective-attention-based) on primary auditory cortex: higher-level areas are known to be strongly influenced by top-down processes, but subcortical areas are often assumed to perform strictly bottom-up processing. Fortunately, recent advances have made it easier to isolate the neural activity of primary auditory cortex from other areas. In this perspective, we focus on time-locked responses to stimulus features in the high gamma band (70-150 Hz) and with early cortical latency (∼40 ms), intermediate between subcortical and higher-level areas. We review recent findings from physiological studies employing either repeated simple sounds or continuous speech, obtaining either a frequency following response (FFR) or temporal response function (TRF). The potential roles of top-down processing are underscored, and comparisons with invasive intracranial EEG (iEEG) and animal model recordings are made. We argue that MEG studies employing continuous speech stimuli may offer particular benefits, in that only a few minutes of speech generates robust high gamma responses from bilateral primary auditory cortex, and without measurable interference from subcortical or higher-level areas.

Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic "gate," which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences <8% between states). The processing of deviant tones was also compared in sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13-20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas.

Characteristics of neurons in auditory cortex of monkeys performing a simple auditory task.

The generators of the initial cortical component of somatosensory evoked potentials in response to tibial nerve stimulation (Tib-somatosensory evoked potentials) are still uncertain. The purpose of this study is to localize the generators of it. A 15-year-old boy with intractable parietal lobe epilepsy was studied. Subdural electrodes were chronically implanted for presurgical evaluation of epilepsy surgery, covering the primary motor, primary sensory, and supplementary sensorimotor areas of the right leg. Tib-somatosensory evoked potentials were recorded from these areas. Highly localized prominent positive activities were recorded from electrodes on the primary motor area of the leg at 32.4 to 34.0 milliseconds. No corresponding large negative peak was recorded in any other electrodes. Weak negative activities distributed widely around the postcentral area at 33.2 to 33.6 milliseconds, accompanied by similar but positive activities in the precentral area at 32.8 to 33.2 milliseconds. There was an independent positive field on supplementary sensorimotor areas at 34.0 to 34.8 milliseconds. A small negative peak was also recorded but only from a single electrode within supplementary sensorimotor areas at 34.0 milliseconds. Our data suggest that the initial response of Tib-somatosensory evoked potentials has at least three independent generators: a radial dipole on the primary motor, a tangential dipole on the primary sensory area, and a dipole on the supplementary sensorimotor areas oriented perpendicularly to the mesial hemispheric surface.

Embodied theories of grounded semantics postulate that, when word meaning is first acquired, a link is established between symbol (word form) and corresponding semantic information present in modality-specific—including primary—sensorimotor cortices of the brain. Direct experimental evidence documenting the emergence of such a link (i.e., showing that presentation of a previously unknown, meaningless word sound induces, after learning, category-specific reactivation of relevant primary sensory or motor brain areas), however, is still missing. Here, we present new neuroimaging results that provide such evidence. We taught participants aspects of the referential meaning of previously unknown, senseless novel spoken words (such as “Shruba” or “Flipe”) by associating them with either a familiar action or a familiar object. After training, we used functional magnetic resonance imaging to analyze the participants’ brain responses to the new speech items. We found that hearing the newly learnt object-related word sounds selectively triggered activity in the primary visual cortex, as well as secondary and higher visual areas.These results for the first time directly document the formation of a link between the novel, previously meaningless spoken items and corresponding semantic information in primary sensory areas in a category-specific manner, providing experimental support for perceptual accounts of word-meaning acquisition in the brain.

Behavior exerts a strong influence over sensory responses in the brain. In the auditory cortex, neural responses to self-generated sounds are suppressed, suggesting that prediction may play a critical role in local sensory processing. However, it is unclear whether this phenomenon derives from a precise movement-based prediction or how it affects the neural representation of incoming stimuli. We address these questions by designing a behavioral paradigm where mice learn to expect the predictable acoustic consequences of a simple forelimb movement. Dense neuronal recordings from auditory cortex revealed suppression of neural responses that was strongest for the expected tone during a narrow time window surrounding the specific sound-associated movement. Predictive suppression was concentrated in layers 2/3 and 5, preceded by the arrival of movement information in deep layers, and driven by motor-sensory coupling rather than task engagement, behavioral relevance, or reward association. Despite large-scale suppression at the population level, the auditory cortex retained a sparse representation of the expected self-generated sounds, while a substantial population of auditory cortex neurons in L2/3 and L5 encoded prediction errors. These findings illustrate that expectation, learned through motor-sensory experience, drives layer-specific predictive processing in the mouse auditory cortex.

Behavioral tasks involving auditory cues activate inhibitory neurons within auditory cortex, leading to a reduction in the amplitude of auditory evoked response potentials (ERPs). One hypothesis is that this process, termed "task engagement," may enable context-dependent behaviors. Here we set out to determine (1) whether the medial prefrontal cortex (mPFC) plays a role in task engagement and (2) how task engagement relates to the context-dependent processing of auditory cues in male and female mice performing a decision-making task that can be guided by either auditory or visual cues. We found that, in addition to auditory ERP suppression, task engagement is associated with increased mPFC activity and an increase in theta band (4-7 Hz) synchronization between the mPFC and auditory cortex. Optogenetically inhibiting the mPFC eliminates the task engagement-induced auditory ERP suppression, while also preventing mice from switching between auditory and visual cue-based rules. However, mPFC inhibition, which eliminates task engagement-induced auditory ERP suppression, did not prevent mice from making decisions based on auditory cues. Furthermore, a more specific manipulation, selective disruption of mPFC outputs to the mediodorsal (MD) thalamus, is sufficient to prevent switching between auditory and visual rules but does not affect auditory ERPs. Based on these findings, we conclude that (1) the mPFC contributes to both task engagement and behavioral flexibility; (2) mPFC-MD projections are important for behavioral flexibility but not task engagement; and (3) task engagement, evidenced by the suppression of cortical responses to sensory input, is not required for sensory cue-guided decision making.SIGNIFICANCE STATEMENT When rodents perform choice-selection tasks based on sensory cues, neural responses to these cues are modulated compared with task-free conditions. Here we demonstrate that this phenomenon depends on the prefrontal cortex and thus represents a form of "top-down" regulation. However, we also show that this phenomenon is not critical for task performance, as rodents can make decisions based on specific sensory cues even when the task-dependent modulation of responses to those cues is abolished. Furthermore, disrupting one specific set of prefrontal outputs impairs rule switching but not the task-dependent modulation of sensory responses. These results show that the prefrontal cortex comprises multiple circuits that mediate dissociable functions related to behavioral flexibility and sensory processing.

Categorical sensory representations are critical for many behaviors, including speech perception. In the auditory system, categorical information is thought to arise hierarchically, becoming increasingly prominent in higher-order cortical regions. The neural mechanisms that support this robust and flexible computation remain poorly understood. Here, we studied sound representations in the ferret primary and non-primary auditory cortex while animals engaged in a challenging sound discrimination task. Population-level decoding of simultaneously recorded single neurons revealed that task engagement caused categorical sound representations to emerge in non-primary auditory cortex. In primary auditory cortex, task engagement caused a general enhancement of sound decoding that was not specific to task-relevant categories. These findings are consistent with mixed selectivity models of neural disentanglement, in which early sensory regions build an overcomplete representation of the world and allow neurons in downstream brain regions to flexibly and selectively read out behaviorally relevant, categorical information.

Multisensory connections of monkey auditory cerebral cortex