Cortico-cortical connectivity behind acoustic information transfer to mouse orbitofrontal cortex is sensitive to neuromodulation and displays local sensory gating: relevance in disorders with auditory hallucinations?

Background: Auditory hallucinations (which occur when the distinction between thoughts and perceptions is blurred) are common in psychotic disorders. The orbitofrontal cortex (OFC) may be implicated, because it receives multiple inputs, including sound and affective value via the amygdala, orchestrating complex emotional responses. We aimed to elucidate the circuit and neuromodulatory mechanisms that underlie the processing of emotionally salient auditory stimuli in the OFC — mechanisms that may be involved in auditory hallucinations. Methods: We identified the cortico-cortical connectivity conveying auditory information to the mouse OFC; its sensitivity to neuromodulators involved in psychosis and postpartum depression, such as dopamine and neurosteroids; and its sensitivity to sensory gating (defective in dysexecutive syndromes). Results: Retrograde tracers in OFC revealed input cells in all auditory cortices. Acoustic responses were abolished by pharmacological and chemogenetic inactivation of the above-identified pathway. Acoustic responses in the OFC were reduced by local dopaminergic agonists and neurosteroids. Noticeably, apomorphine action lasted longer in the OFC than in auditory areas, and its effect was modality-specific (augmentation for visual responses), whereas neurosteroid action was sex-specific. Finally, acoustic responses in the OFC reverberated to the auditory association cortex via feedback connections and displayed sensory gating, a phenomenon of local origin, given that it was not detectable in input auditory cortices. Limitations: Although our findings were for mice, connectivity and sensitivity to neuromodulation are conserved across mammals. Conclusion: The corticocortical loop from the auditory association cortex to the OFC is dramatically sensitive to dopamine and neurosteroids. This suggests a clinically testable circuit behind auditory hallucinations. The function of OFC input–output circuits can be studied in mice with targeted and clinically relevant mutations related to their response to emotionally salient sounds.

Attention to speech: Mapping distributed and selective attention systems

Daily life is full of situations where many people converse at the same time. Under these noisy circumstances, individuals can employ different listening strategies to deal with the abundance of sounds around them. In this fMRI study we investigated how applying two different listening strategies – Selective vs. Distributed attention – affects the pattern of neural activity. Specifically, in a simulated ‘cocktail party’ paradigm, we compared brain activation patterns when listeners attend selectively to only one speaker and ignore all others, versus when they distribute their attention and attempt to follow two or four speakers at the same time. Results indicate that the two attention types activate a highly overlapping, bilateral fronto-temporal-parietal network of functionally connected regions. This network includes auditory association cortex (bilateral STG/STS) and higher-level regions related to speech processing and attention (bilateral IFG/insula, right MFG, left IPS). Within this network, responses in specific areas were modulated by the type of attention required. Specifically, auditory and speech-processing regions exhibited higher activity during Distributed attention, whereas fronto-parietal regions were activated more strongly during Selective attention. This pattern suggests that a common perceptual-attentional network is engaged when dealing with competing speech-inputs, regardless of the specific task at hand. At the same time, local activity within nodes of this network varies when implementing different listening strategies, reflecting the different cognitive demands they impose. These results nicely demonstrate the system’s flexibility to adapt its internal computations to accommodate different task requirements and listener goals.Significance StatementHearing many people talk simultaneously poses substantial challenges for the human perceptual and cognitive systems. We compared neural activity when listeners applied two different listening strategy to deal with these competing inputs: attending selectively to one speaker vs. distributing attention among all speakers. A network of functionally connected brain regions, involved in auditory processing, language processing and attentional control was activated when applying both attention types. However, activity within this network was modulated by the type of attention required and the number of competing speakers. These results suggest a common ‘attention to speech’ network, providing the computational infrastructure to deal effectively with multi-speaker input, but with sufficient flexibility to implement different prioritization strategies and to adapt to different listener goals.

Differences in Clinical Characteristics and Brain Activity between Patients with Low- and High-Frequency Tinnitus

This study was aimed at delineating and comparing differences in clinical characteristics and brain activity between patients with low- and high-frequency tinnitus (LFT and HFT, respectively) using high-density electroencephalography (EEG). This study enrolled 3217 patients with subjective tinnitus who were divided into LFT (frequency<4000 Hz) and HFT (≥4000 Hz) groups. Data regarding medical history, Tinnitus Handicap Inventory, tinnitus matching, and hearing threshold were collected from all patients. Twenty tinnitus patients and 20 volunteers were subjected to 256-channel EEG, and neurophysiological differences were evaluated using standardized low-resolution brain electromagnetic tomography (sLORETA) source-localized EEG recordings. Significant differences in sex (p<0.001), age (p=0.022), laterality (p<0.001), intensity (p<0.001), tinnitus type (p<0.001), persistent tinnitus (p=0.04), average threshold (p<0.001), and hearing loss (p=0.028) were observed between LFT and HFT groups. The tinnitus pitch only appeared to be correlated with the threshold of the worst hearing loss in the HFT group. Compared with the controls, the LFT group exhibited increased gamma power (p<0.05), predominantly in the posterior cingulate cortex (PCC, BA31), whereas the HFT group had significantly decreased alpha1 power (p<0.05) in the angular gyrus (BA39) and auditory association cortex (BA22). Higher gamma linear connectivity between right BA39 and right BA41 was observed in the HFT group relative to controls (t=3.637, p=0.027). Significant changes associated with increased gamma in the LFT group and decreased alpha1 in the HFT group indicate that tinnitus pitch is crucial for matching between the tinnitus and control groups. Differences of band frequency energy in brain activity levels may contribute to the clinical characteristics and internal tinnitus “spectrum” differences.

Audiovisual Speech Enhancement via Cross-Modal Suppression of Auditory Association Cortex by Visual Speech

INTRODUCTION Speech is multisensory. The addition of visual speech to auditory speech greatly improves comprehension, especially under noisy auditory conditions. However, the neural mechanism for this visual enhancement of auditory speech is poorly understood. We used electrocorticography (ECoG) to study how auditory, visual, and audiovisual speech is processed in the posterior superior temporal gyrus (pSTG), an area of auditory association cortex involved in audiovisual speech integration. We hypothesized that early visual mouth movements modulate audiovisual speech integration through a mechanism of cross-modal suppression, suggesting that the pSTG response to early mouth movements should correlate with comprehension benefits gained by the addition of visual speech to auditory speech. METHODS Words were presented under auditory-only (AUD), visual-only (VIS), and audiovisual (AV) conditions to epilepsy patients (n = 8) implanted with intracranial electrodes for phase-2 monitoring. We measured high-frequency broadband activity (75-150 Hz), a marker for local neuronal firing, in 28 electrodes over the pSTG. RESULTS The early neural response to visual-only words was compared to the reduction in neural response seen from AUD to AV words, a reduction correlated with an improvement in speech comprehension that occurs with the addition of visual to auditory speech. In words that showed a comprehension benefit with the addition of visual speech, there was a strong early response to visual speech and a correlation between early visual response and the AUD-AV difference (r = 0.64, P = 104). In words where visual speech did not provide any comprehension benefit, there was a weak early visual response and no correlation (r = 0.18, P = .35). CONCLUSION Words with a visual speech comprehension benefit also elicit a strong neural response to early visual speech in pSTG, while words with no comprehension benefit do not cause a strong early response. This suggests that cross-modal suppression of auditory association cortex (pSTG) by early visual plays an important role in audiovisual speech perception.

The visual speech head start improves perception and reduces superior temporal cortex responses to auditory speech

Visual information about speech content from the talker’s mouth is often available before auditory information from the talker's voice. Here we examined perceptual and neural responses to words with and without this visual head start. For both types of words, perception was enhanced by viewing the talker's face, but the enhancement was significantly greater for words with a head start. Neural responses were measured from electrodes implanted over auditory association cortex in the posterior superior temporal gyrus (pSTG) of epileptic patients. The presence of visual speech suppressed responses to auditory speech, more so for words with a visual head start. We suggest that the head start inhibits representations of incompatible auditory phonemes, increasing perceptual accuracy and decreasing total neural responses. Together with previous work showing visual cortex modulation (Ozker et al., 2018b) these results from pSTG demonstrate that multisensory interactions are a powerful modulator of activity throughout the speech perception network.

Cross-modal Suppression of Auditory Association Cortex by Visual Speech as a Mechanism for Audiovisual Speech Perception

Vision provides a perceptual head start for speech perception because most speech is “mouth-leading”: visual information from the talker’s mouth is available before auditory information from the voice. However, some speech is “voice-leading” (auditory before visual). Consistent with a model in which vision modulates subsequent auditory processing, there was a larger perceptual benefit of visual speech for mouth-leading vs. voice-leading words (28% vs. 4%). The neural substrates of this difference were examined by recording broadband high-frequency activity from electrodes implanted over auditory association cortex in the posterior superior temporal gyrus (pSTG) of epileptic patients. Responses were smaller for audiovisual vs. auditory-only mouth-leading words (34% difference) while there was little difference (5%) for voice-leading words. Evidence for cross-modal suppression of auditory cortex complements our previous work showing enhancement of visual cortex (Ozker et al., 2018b) and confirms that multisensory interactions are a powerful modulator of activity throughout the speech perception network.Impact StatementHuman perception and brain responses differ between words in which mouth movements are visible before the voice is heard and words for which the reverse is true.

Adaptation of high-gamma responses in human auditory association cortex

This study investigates adaptation of high-frequency cortical responses [>60 Hz; high-gamma (HG)] to simple and complex sounds in human nonprimary auditory cortex. We used intracranial electrocorticographic recordings to measure event-related changes in HG power as a function of stimulus probability. Tone and speech stimuli were presented in a series of traditional oddball and control paradigms. We hypothesized that HG power attenuates with stimulus repetition over multiple concurrent time scales in auditory association cortex. Time-frequency analyses were performed to identify auditory-responsive sites. Single-trial analyses and quantitative modeling were then used to measure trial-to-trial changes in HG power for high (frequent), low (infrequent), and equal (control) stimulus probabilities. Results show strong reduction of HG responses to frequently repeated tones and speech, with no differences in responses to infrequent and equal-probability stimuli. Adaptation of the HG frequent response, and not stimulus-acoustic differences or deviance-detection enhancement effects, accounted for the differential responses observed for frequent and infrequent sounds. Adaptation of HG responses showed a rapid onset (less than two trials) with slower adaptation between consecutive, repeated trials (2–10 s) and across trials in a stimulus block (∼7 min). The auditory-evoked N100 response also showed repetition-related adaptation, consistent with previous human scalp and animal single-unit recordings. These findings indicate that HG responses are highly sensitive to the regularities of simple and complex auditory events and show adaptation on multiple concurrent time scales in human auditory association cortex.