Modulation Of Auditory Cortex Research Articles

Direct piriform-to-auditory cortical projections shape auditory-olfactory integration.

In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory-olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake male or female mice, we found that odors modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel role of piriform-to-auditory cortical circuitry in shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory-olfactory integration.Significance Statement All living organisms exist within multisensory environments, yet there is a lack in our understanding of how the brain integrates multisensory information. This work highlights a direct piriform-to-auditory cortical circuit governing auditory-olfactory integration. Our results shed new light on a relatively understudied area of multisensory research, promising a more robust understanding of how animals and humans perceive and interact within complex environments.

Movement-Related Modulation in Mouse Auditory Cortex Is Widespread Yet Locally Diverse.

Neurons in the mouse auditory cortex are strongly influenced by behavior, including both suppression and enhancement of sound-evoked responses during movement. The mouse auditory cortex comprises multiple fields with different roles in sound processing and distinct connectivity to movement-related centers of the brain. Here, we asked whether movement-related modulation in male mice might differ across auditory cortical fields, thereby contributing to the heterogeneity of movement-related modulation at the single-cell level. We used wide-field calcium imaging to identify distinct cortical fields and cellular-resolution two-photon calcium imaging to visualize the activity of layer 2/3 excitatory neurons within each field. We measured each neuron's responses to three sound categories (pure tones, chirps, and amplitude-modulated white noise) as mice rested and ran on a non-motorized treadmill. We found that individual neurons in each cortical field typically respond to just one sound category. Some neurons are only active during rest and others during locomotion, and those that are responsive across conditions retain their sound-category tuning. The effects of locomotion on sound-evoked responses vary at the single-cell level, with both suppression and enhancement of neural responses, and the net modulatory effect of locomotion is largely conserved across cortical fields. Movement-related modulation in auditory cortex also reflects more complex behavioral patterns, including instantaneous running speed and nonlocomotor movements such as grooming and postural adjustments, with similar patterns seen across all auditory cortical fields. Our findings underscore the complexity of movement-related modulation throughout the mouse auditory cortex and indicate that movement-related modulation is a widespread phenomenon.

Recovery of auditory evoked response attentional gain modulation following the first psychotic episode indexes improvements in symptom severity.

Attentional control of auditory N100/M100 gain is reduced in individuals with first-episode psychosis (FEP). Persistent problems with executive modulation of auditory sensory activity may impact multiple aspects of psychosis. As a follow-up to our prior work reporting deficits in attentional M100 gain modulation in auditory cortex, we examined changes in M100 gain modulation longitudinally, and further examined relationships between auditory M100 and symptoms of psychosis. We compared auditory M100 in auditory sensory cortex between 21 FEP and 29 matched healthy participants and between timepoints separated by 220 ± 100 days. Magnetoencephalography data were recorded while participants alternately attended or ignored tones in an auditory oddball task. M100 was measured as the average of 80-140 ms post-stimulus in source-localized evoked responses within bilateral auditory cortex. Symptoms were assessed using the PANSS and PSYRATS. M100 amplitudes, attentional modulation of M100 amplitudes, and symptom severity all improved in FEP over time. Further, improvement in M100 modulation correlated with improvements in negative symptoms (PANSS) as well as physical, cognitive, and emotional components of hallucinations (PSYRATS). Conversely, improvements in the overall size of the M100, rather than the difference between active and passive M100 amplitudes, were related to worsening of positive symptoms (PANSS) and physical components of hallucinations. Results indicate a link between symptoms (particularly auditory hallucinations) and auditory cortex neurophysiology in FEP, where auditory attention and auditory sensation have opposed relationships to symptom change. These findings may inform current models of psychosis etiology and could provide nonpharmaceutical avenues for early intervention.

Functional connectivity and gray matter deficits within the auditory attention circuit in first-episode psychosis.

Selective attention deficits in first episode of psychosis (FEP) can be indexed by impaired attentional modulation of auditory M100. It is unknown if the pathophysiology underlying this deficit is restricted to auditory cortex or involves a distributed attention network. We examined the auditory attention network in FEP. MEG was recorded from 27 FEP and 31 matched healthy controls (HC) while alternately ignoring or attending tones. A whole-brain analysis of MEG source activity during auditory M100 identified non-auditory areas with increased activity. Time-frequency activity and phase-amplitude coupling were examined in auditory cortex to identify the attentional executive carrier frequency. Attention networks were defined by phase-locking at the carrier frequency. Spectral and gray matter deficits in the identified circuits were examined in FEP. Attention-related activity was identified in prefrontal and parietal regions, markedly in precuneus. Theta power and phase coupling to gamma amplitude increased with attention in left primary auditory cortex. Two unilateral attention networks were identified with precuneus seeds in HC. Network synchrony was impaired in FEP. Gray matter thickness was reduced within the left hemisphere network in FEP but did not correlate with synchrony. Several extra-auditory attention areas with attention-related activity were identified. Theta was the carrier frequency for attentional modulation in auditory cortex. Left and right hemisphere attention networks were identified, with bilateral functional deficits and left hemisphere structural deficits, though FEP showed intact auditory cortex theta phase-gamma amplitude coupling. These novel findings indicate attention-related circuitopathy early in psychosis potentially amenable to future non-invasive interventions.

Interaction of the effects associated with auditory-motor integration and attention-engaging listening tasks

A number of previous studies have implicated regions in posterior auditory cortex (AC) in auditory-motor integration during speech production. Other studies, in turn, have shown that activation in AC and adjacent regions in the inferior parietal lobule (IPL) is strongly modulated during active listening and depends on task requirements. The present fMRI study investigated whether auditory-motor effects interact with those related to active listening tasks in AC and IPL. In separate task blocks, our subjects performed either auditory discrimination or 2-back memory tasks on phonemic or nonphonemic vowels. They responded to targets by either overtly repeating the last vowel of a target pair, overtly producing a given response vowel, or by pressing a response button. We hypothesized that the requirements for auditory-motor integration, and the associated activation, would be stronger during repetition than production responses and during repetition of nonphonemic than phonemic vowels. We also hypothesized that if auditory-motor effects are independent of task-dependent modulations, then the auditory-motor effects should not differ during discrimination and 2-back tasks. We found that activation in AC and IPL was significantly modulated by task (discrimination vs. 2-back), vocal-response type (repetition vs. production), and motor-response type (vocal vs. button). Motor-response and task effects interacted in IPL but not in AC. Overall, the results support the view that regions in posterior AC are important in auditory-motor integration. However, the present study shows that activation in wide AC and IPL regions is modulated by the motor requirements of active listening tasks in a more general manner. Further, the results suggest that activation modulations in AC associated with attention-engaging listening tasks and those associated with auditory-motor performance are mediated by independent mechanisms.

Asymmetric Interhemispheric Transfer in the Auditory Network: Evidence from TMS, Resting-State fMRI, and Diffusion Imaging.

Hemispheric asymmetries in human auditory cortical function and structure are still highly debated. Brain stimulation approaches can complement correlational techniques by uncovering causal influences. Previous studies have shown asymmetrical effects of transcranial magnetic stimulation (TMS) on task performance, but it is unclear whether these effects are task-specific or reflect intrinsic network properties. To test how modulation of auditory cortex (AC) influences functional networks and whether this influence is asymmetrical, the present study measured resting-state fMRI connectivity networks in 17 healthy volunteers before and immediately after TMS (continuous theta burst stimulation) to the left or right AC, and the vertex as a control. We also examined the relationship between TMS-induced interhemispheric signal propagation and anatomical properties of callosal auditory fibers as measured with diffusion-weighted MRI. We found that TMS to the right AC, but not the left, resulted in widespread connectivity decreases in auditory- and motor-related networks in the resting state. Individual differences in the degree of change in functional connectivity between auditory cortices after TMS applied over the right AC were negatively related to the volume of callosal auditory fibers. The findings show that TMS-induced network modulation occurs, even in the absence of an explicit task, and that the magnitude of the effect differs across individuals as a function of callosal structure, supporting a role for the corpus callosum in mediating functional asymmetry. The findings support theoretical models emphasizing hemispheric differences in network organization and are of practical significance in showing that brain stimulation studies need to take network-level effects into account.

The effect of precision and power grips on activations in human auditory cortex.

The neuroanatomical pathways interconnecting auditory and motor cortices play a key role in current models of human auditory cortex (AC). Evidently, auditory-motor interaction is important in speech and music production, but the significance of these cortical pathways in other auditory processing is not well known. We investigated the general effects of motor responding on AC activations to sounds during auditory and visual tasks (motor regions were not imaged). During all task blocks, subjects detected targets in the designated modality, reported the relative number of targets at the end of the block, and ignored the stimuli presented in the opposite modality. In each block, they were also instructed to respond to targets either using a precision grip, power grip, or to give no overt target responses. We found that motor responding strongly modulated AC activations. First, during both visual and auditory tasks, activations in widespread regions of AC decreased when subjects made precision and power grip responses to targets. Second, activations in AC were modulated by grip type during the auditory but not during the visual task. Further, the motor effects were distinct from the present strong attention-related modulations in AC. These results are consistent with the idea that operations in AC are shaped by its connections with motor cortical regions.

Unilateral Auditory Cortex Lesions Impair or Improve Discrimination Learning of Amplitude Modulated Sounds, Depending on Lesion Side

A fundamental principle of brain organization is bilateral symmetry of structures and functions. For spatial sensory and motor information processing, this organization is generally plausible subserving orientation and coordination of a bilaterally symmetric body. However, breaking of the symmetry principle is often seen for functions that depend on convergent information processing and lateralized output control, e.g. left hemispheric dominance for the linguistic speech system. Conversely, a subtle splitting of functions into hemispheres may occur if peripheral information from symmetric sense organs is partly redundant, e.g. auditory pattern recognition, and therefore allows central conceptualizations of complex stimuli from different feature viewpoints, as demonstrated e.g. for hemispheric analysis of frequency modulations in auditory cortex (AC) of mammals including humans. Here we demonstrate that discrimination learning of rapidly but not of slowly amplitude modulated tones is non-uniformly distributed across both hemispheres: While unilateral ablation of left AC in gerbils leads to impairment of normal discrimination learning of rapid amplitude modulations, right side ablations lead to improvement over normal learning. These results point to a rivalry interaction between both ACs in the intact brain where the right side competes with and weakens learning capability maximally attainable by the dominant left side alone.

Sensitivity of human auditory cortex to rapid frequency modulation revealed by multivariate representational similarity analysis.

Functional Magnetic Resonance Imaging (fMRI) was used to investigate the extent, magnitude, and pattern of brain activity in response to rapid frequency-modulated sounds. We examined this by manipulating the direction (rise vs. fall) and the rate (fast vs. slow) of the apparent pitch of iterated rippled noise (IRN) bursts. Acoustic parameters were selected to capture features used in phoneme contrasts, however the stimuli themselves were not perceived as speech per se. Participants were scanned as they passively listened to sounds in an event-related paradigm. Univariate analyses revealed a greater level and extent of activation in bilateral auditory cortex in response to frequency-modulated sweeps compared to steady-state sounds. This effect was stronger in the left hemisphere. However, no regions showed selectivity for either rate or direction of frequency modulation. In contrast, multivoxel pattern analysis (MVPA) revealed feature-specific encoding for direction of modulation in auditory cortex bilaterally. Moreover, this effect was strongest when analyses were restricted to anatomical regions lying outside Heschl's gyrus. We found no support for feature-specific encoding of frequency modulation rate. Differential findings of modulation rate and direction of modulation are discussed with respect to their relevance to phonetic discrimination.

Representations of pitch and slow modulation in auditory cortex

Iterated ripple noise (IRN) is a type of pitch-evoking stimulus that is commonly used in neuroimaging studies of pitch processing. When contrasted with a spectrally matched Gaussian noise, it is known to produce a consistent response in a region of auditory cortex that includes an area antero-lateral to the primary auditory fields (lateral Heschl's gyrus). The IRN-related response has often been attributed to pitch, although recent evidence suggests that it is more likely driven by slowly varying spectro-temporal modulations not related to pitch. The present functional magnetic resonance imaging (fMRI) study showed that both pitch-related temporal regularity and slow modulations elicited a significantly greater response than a baseline Gaussian noise in an area that has been pre-defined as pitch-responsive. The region was sensitive to both pitch salience and slow modulation salience. The responses to pitch and spectro-temporal modulations interacted in a saturating manner, suggesting that there may be an overlap in the populations of neurons coding these features. However, the interaction may have been influenced by the fact that the two pitch stimuli used (IRN and unresolved harmonic complexes) differed in terms of pitch salience. Finally, the results support previous findings suggesting that the cortical response to IRN is driven in part by slow modulations, not by pitch.

Invariance of firing rate and field potential dynamics to stimulus modulation rate in human auditory cortex

The effect of stimulus modulation rate on the underlying neural activity in human auditory cortex is not clear. Human studies (using both invasive and noninvasive techniques) have demonstrated that at the population level, auditory cortex follows stimulus envelope. Here we examined the effect of stimulus modulation rate by using a rare opportunity to record both spiking activity and local field potentials (LFP) in auditory cortex of patients during repeated presentations of an audio-visual movie clip presented at normal, double, and quadruple speeds. Mean firing rate during evoked activity remained the same across speeds and the temporal response profile of firing rate modulations at increased stimulus speeds was a linearly scaled version of the response during slower speeds. Additionally, stimulus induced power modulation of local field potentials in the high gamma band (64-128 Hz) exhibited similar temporal scaling as the neuronal firing rate modulations. Our data confirm and extend previous studies in humans and anesthetized animals, supporting a model in which both firing rate, and high-gamma LFP power modulations in auditory cortex follow the temporal envelope of the stimulus across different modulation rates.

Interaction of speech and script in human auditory cortex: Insights from neuro-imaging and effective connectivity

In addition to visual information from the face of the speaker, a less natural, but nowadays extremely important visual component of speech is its representation in script. In this review, neuro-imaging studies are examined which were aimed to understand how speech and script are associated in the adult “literate” brain. The reviewed studies focused on the role of different stimulus and task factors and effective connectivity between different brain regions. The studies will be summarized in a neural mechanism for the integration of speech and script that can serve as a basis for future studies addressing (the failure of) literacy acquisition. In this proposed mechanism, speech sound processing in auditory cortex is modulated by co-presented visual letters, depending on the congruency of the letter–sound pairs. Other factors of influence are temporal correspondence, input quality and task instruction. We present results showing that the modulation of auditory cortex is most likely mediated by feedback from heteromodal areas in the superior temporal cortex, but direct influences from visual cortex are not excluded. The influence of script on speech sound processing occurs automatically and shows extended development during reading acquisition. This review concludes with suggestions to answer currently still open questions to get closer to understanding the neural basis of normal and impaired literacy.

Level Dependence of Contextual Modulation in Auditory Cortex

Responses of cortical neurons to sensory stimuli within their receptive fields can be profoundly altered by the stimulus context. In visual and somatosensory cortex, contextual interactions have been shown to change sign from facilitation to suppression depending on stimulus strength. Contextual modulation of high-contrast stimuli tends to be suppressive, but for low-contrast stimuli tends to be facilitative. This trade-off may optimize contextual integration by cortical cells and has been suggested to be a general feature of cortical processing, but it remains unknown whether a similar phenomenon occurs in auditory cortex. Here we used whole cell and single-unit recordings to investigate how contextual interactions in auditory cortical neurons depend on the relative intensity of masker and probe stimuli in a two-tone stimulus paradigm. We tested the hypothesis that relatively low-level probes should show facilitation, whereas relatively high-level probes should show suppression. We found that contextual interactions were primarily suppressive across all probe levels, and that relatively low-level probes were subject to stronger suppression than high-level probes. These results were virtually identical for spiking and subthreshold responses. This suggests that, unlike visual cortical neurons, auditory cortical neurons show maximal suppression rather than facilitation for relatively weak stimuli.

Remapping Auditory-Motor Representations in Voice Production

Evidence regarding visually guided limb movements suggests that the motor system learns and maintains neural maps between motor commands and sensory feedback. Such systems are hypothesized to be used in a feed-forward control strategy that permits precision and stability without the delays of direct feedback control. Human vocalizations involve precise control over vocal and respiratory muscles. However, little is known about the sensorimotor representations underlying speech production. Here, we manipulated the heard fundamental frequency of the voice during speech to demonstrate learning of auditory-motor maps. Mandarin speakers repeatedly produced words with specific pitch patterns (tone categories). On each successive utterance, the frequency of their auditory feedback was increased by 1/100 of a semitone until they heard their feedback one full semitone above their true pitch. Subjects automatically compensated for these changes by lowering their vocal pitch. When feedback was unexpectedly returned to normal, speakers significantly increased the pitch of their productions beyond their initial baseline frequency. This adaptation was found to generalize to the production of another tone category. However, results indicate that a more robust adaptation was produced for the tone that was spoken during feedback alteration. The immediate aftereffects suggest a global remapping of the auditory-motor relationship after an extremely brief training period. However, this learning does not represent a complete transformation of the mapping; rather, it is in part target dependent.

Auditory event-related potentials during target detection are abnormal in mild cognitive impairment

Objective: To define brain activity and behavioral changes in mild cognitive impairment (MCI), an isolated memory deficit in the elderly that is a major risk factor for Alzheimer's disease.Methods: Brain potentials and reaction time were examined in elderly controls (n=12) and MCI (n=15) using a target detection paradigm. Subjects listened to a sequence of tones and responded to high-pitched target tones (P=0.20) that were randomly mixed with low-pitched tones (P=0.80). Measures were a pre-stimulus readiness potential (RP), post-stimulus potentials (P50, N100, P200, N200, P300), and reaction time.Results: Accuracy was equivalent between groups, but there was a trend for longer reaction times in MCI (P=0.08). Two potentials differed between groups: (1) P50 amplitude and latency were significantly increased in MCI, and (2) P300 latency was significantly longer in MCI. Results from two MCI subjects that converted to Alzheimer's disease are also discussed.Conclusions: Brain potentials in MCI subjects during target detection have certain features similar to healthy aging (RP, N100, P200, N200), and other features similar to Alzheimer's disease (delayed P300 latency, slower reaction time). P50 differences in MCI may reflect pathophysiological changes in the modulation of auditory cortex by association cortical regions having neuropathological changes in early Alzheimer's disease.

RESPONSES OF AUDITORY CORTICAL NEURONS TO STIMULI OF CHANGING FREQUENCY.

RESPONSES OF AUDITORY CORTICAL NEURONS TO STIMULI OF CHANGING FREQUENCY.