Disturbed Balance of Inhibitory Signaling Links Hearing Loss and Cognition

Neuronal hyperexcitability in the central auditory pathway linked to reduced inhibitory activity is associated with numerous forms of hearing loss, including noise damage, age-dependent hearing loss, and deafness, as well as tinnitus or auditory processing deficits in autism spectrum disorder (ASD). In most cases, the reduced central inhibitory activity and the accompanying hyperexcitability are interpreted as an active compensatory response to the absence of synaptic activity, linked to increased central neural gain control (increased output activity relative to reduced input). We here suggest that hyperexcitability also could be related to an immaturity or impairment of tonic inhibitory strength that typically develops in an activity-dependent process in the ascending auditory pathway with auditory experience. In these cases, high-SR auditory nerve fibers, which are critical for the shortest latencies and lowest sound thresholds, may have either not matured (possibly in congenital deafness or autism) or are dysfunctional (possibly after sudden, stressful auditory trauma or age-dependent hearing loss linked with cognitive decline). Fast auditory processing deficits can occur despite maintained basal hearing. In that case, tonic inhibitory strength is reduced in ascending auditory nuclei, and fast inhibitory parvalbumin positive interneuron (PV-IN) dendrites are diminished in auditory and frontal brain regions. This leads to deficits in central neural gain control linked to hippocampal LTP/LTD deficiencies, cognitive deficits, and unbalanced extra-hypothalamic stress control. Under these conditions, a diminished inhibitory strength may weaken local neuronal coupling to homeostatic vascular responses required for the metabolic support of auditory adjustment processes. We emphasize the need to distinguish these two states of excitatory/inhibitory imbalance in hearing disorders: (i) Under conditions of preserved fast auditory processing and sustained tonic inhibitory strength, an excitatory/inhibitory imbalance following auditory deprivation can maintain precise hearing through a memory linked, transient disinhibition that leads to enhanced spiking fidelity (central neural gain⇑) (ii) Under conditions of critically diminished fast auditory processing and reduced tonic inhibitory strength, hyperexcitability can be part of an increased synchronization over a broader frequency range, linked to reduced spiking reliability (central neural gain⇓). This latter stage mutually reinforces diminished metabolic support for auditory adjustment processes, increasing the risks for canonical dementia syndromes.

Respiratory Rhythms of the Predictive Mind

All living organisms breathe. Respiratory rhythms sustain biological life, governing the homeostatic exchange of oxygen and carbon dioxide. Until recently however, the influence of breathing on the brain has largely been overlooked. Yet new evidence demonstrates that respiratory rhythms exert surprising, substantive influences on perception, emotion, and cognition, largely through the direct modulation of neural oscillations. Here we synthesize these findings to motivate a new predictive coding model of respiratory brain coupling, in which the breath rhythmically enhances both local and global neural gain, to optimize cognitive and affective processing. Our model further explains how respiratory rhythms interact with the topology of the functional connectome, and we highlight key implications for the computational psychiatry of disordered respiratory and interoceptive inference.

Segmenting and Predicting Musical Phrase Structure Exploits Neural Gain Modulation and Phase Precession

Music, like language, is characterized by hierarchically organized structure that unfolds over time. Music listening therefore requires not only the tracking of notes and beats but also internally constructing high-level musical structures or phrases and anticipating incoming contents. Unlike for language, mechanistic evidence for online musical segmentation and prediction at a structural level is sparse. We recorded neurophysiological data from participants listening to music in its original forms as well as in manipulated versions with locally or globally reversed harmonic structures. We discovered a low-frequency neural component that modulated the neural rhythms of beat tracking and reliably parsed musical phrases. We next identified phrasal phase precession, suggesting that listeners established structural predictions from ongoing listening experience to track phrasal boundaries. The data point to brain mechanisms that listeners use to segment continuous music at the phrasal level and to predict abstract structural features of music.

Attention expedites target selection by prioritizing the neural processing of distractor features

Whether doing the shopping, or driving the car – to navigate daily life, our brain has to rapidly identify relevant color signals among distracting ones. Despite a wealth of research, how color attention is dynamically adjusted is little understood. Previous studies suggest that the speed of feature attention depends on the time it takes to enhance the neural gain of cortical units tuned to the attended feature. To test this idea, we had human participants switch their attention on the fly between unpredicted target color alternatives, while recording the electromagnetic brain response to probes matching the target, a non-target, or a distracting alternative target color. Paradoxically, we observed a temporally prioritized processing of distractor colors. A larger neural modulation for the distractor followed by its stronger attenuation expedited target identification. Our results suggest that dynamic adjustments of feature attention involve the temporally prioritized processing and elimination of distracting feature representations.

Co-occurrence of Hyperacusis Accelerates With Tinnitus Burden Over Time and Requires Medical Care

Although tinnitus represents a major global burden, no causal therapy has yet been established. Ongoing controversies about the neuronal pathophysiology of tinnitus hamper efforts in developing advanced therapies. Hypothesizing that the unnoticed co-occurrence of hyperacusis and differences in the duration of tinnitus may possibly differentially influence the neural correlate of tinnitus, we analyzed 33 tinnitus patients without (T-group) and 20 tinnitus patients with hyperacusis (TH-group). We found crucial differences between the T-group and the TH-group in the increase of annoyance, complaints, tinnitus loudness, and central neural gain as a function of tinnitus duration. Hearing thresholds did not differ between T-group and TH-group. In the TH-group, the tinnitus complaints (total tinnitus score) were significantly greater from early on and the tinnitus intensity distinctly increased over time from ca. 12 to 17 dB when tinnitus persisted more than 5 years, while annoyance responses to normal sound remained nearly constant. In contrast, in the T-group tinnitus complaints remained constant, although the tinnitus intensity declined over time from ca. 27 down to 15 dB beyond 5 years of tinnitus persistence. This was explained through a gradually increased annoyance to normal sound over time, shown by a hyperacusis questionnaire. Parallel a shift from a mainly unilateral (only 17% bilateral) to a completely bilateral (100%) tinnitus percept occurred in the T-group, while bilateral tinnitus dominated in the TH-group from the start (75%). Over time in the T-group, ABR wave V amplitudes (and V/I ratios) remained reduced and delayed. By contrast, in the TH-group especially the ABR wave III and V (and III/I ratio) continued to be enhanced and shortened in response to high-level sound stimuli. Interestingly, in line with signs of an increased co-occurrence of hyperacusis in the T-group over time, ABR wave III also slightly increased in the T-group. The findings disclose an undiagnosed co-occurrence of hyperacusis in tinnitus patients as a main cause of distress and the cause of complaints about tinnitus over time. To achieve urgently needed and personalized therapies, possibly using the objective tools offered here, a systematic sub-classification of tinnitus and the co-occurrence of hyperacusis is recommended.

Musicianship and melodic predictability enhance neural gain in auditory cortex during pitch deviance detection

When listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in synaptic efficacy underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)—and its modulation by context predictability and musical expertise—are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision-weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)—typically related to gain control—or extrinsic connections between A1 and STG—typically related to propagation of prediction and error signals—better explained magnetoencephalography (MEG) responses. We found that, compared to regular sounds, out-of-tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing.Significance statementIn complex auditory contexts, being able to identify informative signals is of paramount importance. Such is the case of music listening, where surprising sounds play a fundamental role in its perceptual, aesthetical, and emotional experience. Crucially, surprising sounds in the pitch dimension are more easily detected and generate stronger cortical responses when melodies are predictable and when the listener is a musician. Using Dynamic Causal Modelling, here we show that such effects arise from a local increase in neural gain within auditory areas, rather than from passing of prediction and error signals between brain regions. Consistent with predictive processing theories, this suggests that the enhanced precision of auditory predictive models—through melodic predictability and musical training—up-regulates the processing of informative error signals in the brain.