Cross-species real time detection of trends in pupil size fluctuation.

Pupillometry is a popular method because pupil size is an easily measured and sensitive marker of neural activity and associated with behavior, cognition, emotion, and perception. Currently, there is no method for monitoring the phases of pupillary fluctuation in real time. We introduce rtPupilPhase - a software that automatically detects trends in pupil size in real time, enabling novel implementations of real time pupillometry towards achieving numerous research and translational goals.

An Inverse Relationship Between Gray Matter Volume and Speech-in-Noise Performance in Tinnitus Patients with Normal Hearing Sensitivity.

Speech-in-noise (SiN) recognition difficulties are often reported in patients with tinnitus. Although brain structural changes such as reduced gray matter (GM) volume in auditory and cognitive processing regions have been reported in the tinnitus population, it remains unclear how such changes influence speech understanding, such as SiN performance. In this study, pure-tone audiometry and Quick Speech-in-Noise test were conducted on individuals with tinnitus and normal hearing and hearing-matched controls. T1-weighted structural MRI images were obtained from all participants. After preprocessing, GM volumes were compared between tinnitus and control groups using whole-brain and region-of-interest analyses. Further, regression analyses were performed to examine the correlation between regional GM volume and SiN scores in each group. The results showed decreased GM volume in the right inferior frontal gyrus in the tinnitus group relative to the control group. In the tinnitus group, SiN performance showed a negative correlation with GM volume in the left cerebellum (Crus I/II) and the left superior temporal gyrus; no significant correlation between SiN performance and regional GM volume was found in the control group. Even with clinically defined normal hearing and comparable SiN performance relative to controls, tinnitus appears to change the association between SiN recognition and regional GM volume. This change may reflect compensatory mechanisms utilized by individuals with tinnitus who maintain behavioral performance.

Cortex-wide neural dynamics predict behavioral states and provide a neural basis for resting-state dynamic functional connectivity.

Although resting-state functional magnetic resonance imaging (fMRI) studies have observed dynamically changing brain-wide networks of correlated activity, fMRI's dependence on hemodynamic signals makes results challenging to interpret. Meanwhile, emerging techniques for real-time recording of large populations of neurons have revealed compelling fluctuations in neuronal activity across the brain that are obscured by traditional trial averaging. To reconcile these observations, we use wide-field optical mapping to simultaneously record pan-cortical neuronal and hemodynamic activity in awake, spontaneously behaving mice. Some components of observed neuronal activity clearly represent sensory and motor function. However, particularly during quiet rest, strongly fluctuating patterns of activity across diverse brain regions contribute greatly to interregional correlations. Dynamic changes in these correlations coincide with changes in arousal state. Simultaneously acquired hemodynamics depict similar brain-state-dependent correlation shifts. These results support a neural basis for dynamic resting-state fMRI, while highlighting the importance of brain-wide neuronal fluctuations in the study of brain state.

Evaluating the Efficacy of a Smartphone App for Tinnitus Relief Using Behavioral and Brain Imaging Measures.

PURPOSE: In this exploratory, open-label study, we used behavioral and brain imaging measures to assess the effectiveness of a smartphone application (ReSound Relief app), which aims to help reduce tinnitus-related distress. METHOD: Fourteen participants with a wide range of tinnitus-related symptoms and who were not currently undergoing any external treatment participated. They completed the 6-month study and reported different levels of engagement with the app. RESULTS: Across a range of tinnitus questionnaires, most participants showed either no change or decrease in tinnitus handicap. Resting-state and task-based functional magnetic resonance imaging (fMRI) data were collected at baseline and the end of the study. Resting-state fMRI of 12 participants revealed alterations in interregional connectivity of default mode, salience, emotion, auditory, and visual processing networks at the end of the intervention period compared to baseline. Ratings of affective sounds (as pleasant, neutral, or unpleasant) were assessed using fMRI, and comparison after 6 months of app usage revealed reduced activity in the left superior temporal gyrus (secondary auditory cortex), right superior occipital gyrus, and left posterior cingulate cortex. Our findings were not significant at a false discovery rate level of p < .05. CONCLUSIONS: The reported changes were not significant, possibly due to the small sample size, heterogeneity of the tinnitus handicap among subjects at the start of the project, and the length of the intervention period. Nevertheless, this study underscores the ease of usage of the app and the potential use of brain imaging to assess changes due to a passive, self-administered intervention for individuals with varying levels of tinnitus severity.

Evaluating the efficacy of hearing aids for tinnitus therapy - A Positron emission tomography study.

Brain imaging studies have revealed neural changes in chronic tinnitus patients that are not restricted to auditory brain areas; rather, the engagement of limbic system structures, attention and memory networks are has been noted. Hearing aids (HA) provide compensation for comorbid hearing loss and may decrease tinnitus-related perception and annoyance. Using resting state positron emission tomography our goal was to analyze metabolic and functional brain changes after six months of effective HA use by patients with chronic tinnitus and associated sensorineural hearing loss. 33 age and hearing loss matched participants with mild/moderate hearing loss were enrolled in this study: 19 with tinnitus, and 14 without tinnitus. Participants with tinnitus of more than 6 months with moderate/severe Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS) scores composed the tinnitus group. A full factorial 2X2 ANOVA was conducted for imaging analysis, with group (tinnitus and controls) and time point (pre-intervention and post-intervention) as factors. Six months after HA fitting, tinnitus scores reduced statistically and clinically. Analysis revealed increased glycolytic metabolism in the left orbitofrontal cortex, right temporal lobe and right hippocampus, and reduced glycolytic metabolism in the left cerebellum and inferior parietal lobe within the tinnitus group. The hearing loss control group showed no significant metabolic changes in the analysis. Parsing out the contribution of tinnitus independent of hearing loss, allowed us to identify areas implicated in declines in tinnitus handicap as a result of the intervention. Brain regions implicated in the present study may be part of chronic tinnitus-specific network.

Salience, emotion, and attention: The neural networks underlying tinnitus distress revealed using music and rest.

In the present study, we used an innovative music-rest interleaved fMRI paradigm to investigate the neural correlates of tinnitus distress. Tinnitus is a poorly-understood hearing disorder where individuals perceive sounds, in the absence of an external source. Although the great majority of individuals habituate to chronic tinnitus and report few symptoms, a minority report debilitating distress and annoyance. Prior research suggests that a diverse set of brain regions, including the attention, the salience, and the limbic networks, play key roles in mediating both the perception of tinnitus and its impact on the individual; however, evidence of the degree and extent of their involvement has been inconsistent. Here, we minimally modified the conventional resting state fMRI by interleaving it with segments of jazz music. We found that the functional connectivity between a set of brain regions-including cerebellum, precuneus, superior/middle frontal gyrus, and primary visual cortex-and seeds in the dorsal attention network, the salience network, and the amygdala, were effective in fractionating the tinnitus patients into two subgroups, characterized by the severity of tinnitus-related distress. Further, our findings revealed cross-modal modulation of the attention and salience networks by the visual modality during the music segments. On average, the more bothersome the reported tinnitus, the stronger was the exhibited inter-network functional connectivity. This study substantiates the essential role of the attention, salience, and limbic networks in tinnitus habituation, and suggests modulation of the attention and salience networks across the auditory and visual modalities as a possible compensatory mechanism for bothersome tinnitus.

A large-scale diffusion imaging study of tinnitus and hearing loss.

Subjective, chronic tinnitus, the perception of sound in the absence of an external source, commonly occurs with many comorbidities, making it a difficult condition to study. Hearing loss, often believed to be the driver for tinnitus, is perhaps one of the most significant comorbidities. In the present study, white matter correlates of tinnitus and hearing loss were examined. Diffusion imaging data were collected from 96 participants-43 with tinnitus and hearing loss (TINHL), 17 with tinnitus and normal hearing thresholds (TINNH), 17 controls with hearing loss (CONHL) and 19 controls with normal hearing (CONNH). Fractional anisotropy (FA), mean diffusivity and probabilistic tractography analyses were conducted on the diffusion imaging data. Analyses revealed differences in FA and structural connectivity specific to tinnitus, hearing loss, and both conditions when comorbid, suggesting the existence of tinnitus-specific neural networks. These findings also suggest that age plays an important role in neural plasticity, and thus may account for some of the variability of results in the literature. However, this effect is not seen in tractography results, where a sensitivity analysis revealed that age did not impact measures of network integration or segregation. Based on these results and previously reported findings, we propose an updated model of tinnitus, wherein the internal capsule and corpus callosum play important roles in the evaluation of, and neural plasticity in response to tinnitus.

Decreased resting perfusion in precuneus and posterior cingulate cortex predicts tinnitus severity.

Functional magnetic resonance imaging has been increasingly used to understand the mechanisms involved in subjective tinnitus; however, researchers have struggled to reach a consensus about a primary mechanistic model to explain tinnitus. While many studies have used functional connectivity of the BOLD signal to understand how patterns of activity change with tinnitus severity, there is much less research on whether there are differences in more fundamental physiology, including cerebral blood flow, which may help inform the BOLD measures. Here, arterial spin labeling was used to measure perfusion in four regions-of-interest, guided by current models of tinnitus, in a sample of 60 tinnitus patients and 31 control subjects. We found global reductions in cerebral perfusion in tinnitus compared with controls. Additionally, we observed a significant negative correlation between tinnitus severity and perfusion. These results demonstrate that examining perfusion from the whole brain may present a complementary tool for studying tinnitus. More research will help better understand the physiology underlying these differences in perfusion.

Comparing Cyclicity Analysis With Pre-established Functional Connectivity Methods to Identify Individuals and Subject Groups Using Resting State fMRI.

The resting state fMRI time series appears to have cyclic patterns, which indicates presence of cyclic interactions between different brain regions. Such interactions are not easily captured by pre-established resting state functional connectivity methods including zero-lag correlation, lagged correlation, and dynamic time warping distance. These methods formulate the functional interaction between different brain regions as similar temporal patterns within the time series. To use information related to temporal ordering, cyclicity analysis has been introduced to capture pairwise interactions between multiple time series. In this study, we compared the efficacy of cyclicity analysis with aforementioned similarity-based techniques in representing individual-level and group-level information. Additionally, we investigated how filtering and global signal regression interacted with these techniques. We obtained and analyzed fMRI data from patients with tinnitus and neurotypical controls at two different days, a week apart. For both patient and control groups, we found that the features generated by cyclicity and correlation (zero-lag and lagged) analyses were more reliable than the features generated by dynamic time warping distance in identifying individuals across visits. The reliability of all features, except those generated by dynamic time warping, improved as the global signal was regressed. Nevertheless, removing fluctuations >0.1 Hz deteriorated the reliability of all features. These observations underscore the importance of choosing appropriate preprocessing steps while evaluating different analytical methods in describing resting state functional interactivity. Further, using different machine learning techniques including support vector machines, discriminant analyses, and convolutional neural networks, our results revealed that the manifestation of the group-level information within all features was not sufficient enough to dissociate tinnitus patients from controls with high sensitivity and specificity. This necessitates further investigation regarding the representation of group-level information within different features to better identify tinnitus-related alternation in the functional organization of the brain. Our study adds to the growing body of research on developing diagnostic tools to identify neurological disorders, such as tinnitus, using resting state fMRI data.