Research's Attempt to Objectively Assess Tinnitus

[Frédéric]

The relationship of high-frequency distortion product otoacoustic emission (DPOAE) values with hematological parameters in tinnitus patients

Abstract
Purpose
In this study, we aimed to investigate whether there is any positive or negative correlation between high-frequency distortion product otoacoustic emission (DPOAE) values and mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR) in tinnitus patients.

Methods
The study was performed with 52 volunteers (27 females, 25 males) aged between 35 and 50 years who presented with tinnitus to the otolaryngology outpatient clinic of a tertiary care center. Pure voice audiometric examination, DPOAE measurement, complete blood count values of the study participants were examined.

Results
In both ears, a significant and negative correlation was observed between 4000 and 8000 Hz airway and 4000 Hz bone conduction pathways with NLR rates (p < 0.05). A statistically significant relationship was found between the bone conduction pathway PTA and discrimination values for both ears and NLR s (p < 0.05). A positive correlation was detected between NLRs and DPOAE measurements recorded at 4444 Hz, 5000 Hz, 8000 Hz, 8889 Hz, 10,000 Hz and 11,429 Hz frequencies in the right and 4444 Hz, 5000 Hz, 6154 Hz, 8000 Hz, 10,000 Hz and 11,429 Hz frequencies in the left ears, respectively (p < 0.05).

Conclusions
We concluded that there is a significant correlation between high-frequency pure tone audiometry measurements and high frequency DPOAE measurements and NLR. Further studies are needed to determine the utility of NLR as a marker for the recognition and follow-up of hearing loss in patients with tinnitus.

Source: https://link.springer.com/article/10.1007/s00405-019-05585-4

 

[Frédéric]

Chronic tinnitus and the limbic system: Reappraising brain structural effects of distress and affective symptoms

Highlights
Chronic tinnitus is associated with high psychiatric co-morbidity and distress.
Parahippocamal grey matter is associated with tinnitus rather than distress.
Psychiatric co-morbidity modulates tinnitus-related structural patterns.

Abstract
Chronic tinnitus has been associated with brain structural changes in both the auditory system as well as limbic system. While there is considerable inconsistency across brain structural findings, growing evidence suggests that distress and other non-auditory symptoms modulate effects. In this study we addressed this issue, testing the hypothesis that limbic changes in tinnitus relate to both disease-related distress as well as co-morbid psychopathology. We obtained high-resolution structural magnetic resonance imaging (MRI) scans from a total of 125 subjects: 59 patients with bilateral chronic tinnitus (29 with a co-morbid psychiatric condition, 30 without), 40 healthy controls and 26 psychiatric controls with depression/anxiety disorders (without tinnitus). Voxel-based morphometry with the CAT12 software package was used to analyse data. First, we analysed data based on a 2 × 2 factorial design (tinnitus; psychiatric co-morbidity), showing trend-level effects for tinnitus in ROI analyses of the anterior cingulate cortex and superior/transverse temporal gyri, and for voxel-based analysis in the left parahippocampal cortex. Multiple regression analyses showed that the parahippocampal finding was mostly predicted by tinnitus rather than (dimensional) psychopathology ratings. Comparing only low-distress tinnitus patients (independent of co-morbid conditions) with healthy controls also showed reduced left parahippocampal grey matter. Our findings demonstrate that depression and anxiety (not only subjective distress) are major modulators of brain structural effects in tinnitus, calling for a stronger consideration of psychopathology in future neurobiological and clinical studies of tinnitus.

full text: https://www.sciencedirect.com/science/article/pii/S2213158219303262

 

[Hazel]

Hi @Frédéric, I just want to say that @Markku and I really appreciate you starting this thread! I believe that finding objective measures of tinnitus is key to finding a cure, so thank you for putting in the time and effort to collect those studies!

If you're interested in working with us on some other research focused projects, let us know - we have a few interesting projects in the pipeline. Send me and Markku a PM if you're interested.

 

[Frédéric]

Hi @Hazel, @Markku

Hazel, I cannot send you a PM, I have got the message: "You may not start a conversation with the following recipients: Hazel."

So I replied to you publicly.

Many thanks for your thanks. I know you are looking for volunteers, but honestly I have none of the skills you listed in the link: https://www.tinnitustalk.com/threads/become-a-tinnitus-talk-advocate.7694/
(My initial training is civil engineering, so no relation with these skills). Plus my understanding of oral English is poor.

So I do what I can do: prospecting on medical research. Some time ago, I sent to Markku a report on clinical trials not yet listed on the forum (see attached file), I guess he was very busy so he could not edit it. I suggest you can give me an editing access to the clinical trials topic so I will be able to update it.

To sum up, I can do some work in this area (research). So I am interested, tell me more about.

 

[Autumnly]

Not sure if this study fits into this thread or rather belongs in a thread about transcranial direct current stimulation.

An Exploratory Study on the Use of Event-Related Potentials as an Objective Measure of Auditory Processing and Therapy Effect in Patients With Tinnitus
A Transcranial Direct Current Stimulation Study
Jacquemin, Laure; Mertens, Griet; Van de Heyning, Paul; Vanderveken, Olivier M.; Topsakal, Vedat; De Hertogh, Willem; Michiels, Sarah Beyers, Jolien; Moyaert, Julie; Van Rompaey, Vincent; Gilles, Annick
Otology & Neurotology: September 6, 2019 - Volume Publish Ahead of Print - Issue - p

Objective: Treatment effect in tinnitus research is commonly evaluated by use of self-report questionnaires. As this is a solely subjective assessment method, the need for an objective measurement is paramount to genuinely evaluate the effects of therapeutic interventions. The current study explores the value of event-related potentials(ERPs) in the evaluation of high-definition transcranial direct current stimulation (HD-tDCS) for tinnitus treatment.

Results: The results show a significant shortening of the N1, P2, N2, and P3 latencies after HD-tDCS treatment. Moreover, the increased amplitude of the P2 and N2 peaks result in more salient and clear peaks, with the amplitude of N2 being significant larger after HD-tDCS. However, the ERP changes are not significantly correlated with the change in tinnitus functional index (TFI) total score.

Conclusions: The current study was the first to explore ERPs as objective measure in a study with HD-tDCS in tinnitus patients. Adding ERPs to the outcome measures in tinnitus research may lead to a better understanding of the therapeutic effect in the future. The results showed a shortening of ERP latencies and an increased N2 amplitude, possibly reflecting more effective sound processing with higher recruitment of synchronized neurons in the auditory cortex. Future studies should elaborate on these results, by collecting control data and adding a sham group, to provide a better insight in the underlying mechanism of the ERP changes after tinnitus treatment.

 

[TuxedoCat]

Not sure if this study fits into this thread or rather belongs in a thread about transcranial direct current stimulation.

Hi Autumnly, Is there a task force, either within TRI or some other organization, charged with finding or recommending/adopting an objective measure of tinnitus? I'm getting the sense that organizing tinnitus researchers is like herding cats or organizing earthworms. -TC

 

[Autumnly]

Hi Autumnly, Is there a task force, either within TRI or some other organization, charged with finding or recommending/adopting an objective measure of tinnitus? I'm getting the sense that organizing tinnitus researchers is like herding cats or organizing earthworms. -TC

That's a really good question, I'm not sure if anyone's officially charged with finding an objective measure of tinnitus but I know that Gregory Ginnan from TIN-ACT is trying to find "an objective, physiological marker for the tinnitus percept in general, as well as an estimate of the perceived tinnitus pitch, rather than being reliant on subjective questionnaires".

 

[Frédéric]

Oups I realized I fogot to attach the file, sorry.

 

[Frédéric]

Disrupted intraregional brain activity and functional connectivity in unilateral acute tinnitus patients with hearing loss
Gang-Ping Zhou1,

Xin-Yi Shi2, Heng-Le Wei1, Li-Jie Qu1, Yu-Sheng Yu1, Qing-Qing Zhou1, Xindao Yin3,

Hong Zhang1* and Yue-Jin Tao2*

• 1Department of Radiology, The Affiliated Jiangning Hospital, Nanjing Medical University, China
• 2Nanjing Jiangning Hospital, China
• 3Department of Radiology, Nanjing First Hospital, Nanjing Medical University, China

Purpose: The present study combined fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo) and functional connectivity (FC) to explore brain functional abnormalities in acute tinnitus patients (AT) with hearing loss.
Methods: We recruited twenty-eight AT patients and 31 healthy controls (HCs) and ran resting-state functional magnetic resonance imaging (fMRI) scans. fALFF, ReHo, and FC were conducted and compared between AT patients and HCs. After that, we calculated correlation analyses among abnormal fALFF, ReHo, FC and clinical data in AT patients.
Results: Compared with HCs, acute tinnitus patients showed increased fALFF values in the right inferior temporal gyrus (ITG). In contrast, significantly decreased ReHo values were observed in the cerebellar vermis, the right calcarine cortex, the right precuneus, the right supramarginal gyrus (SMG) and the right middle frontal gyrus (MFG). Based on the differences in the fALFF and ReHo maps, the latter of which we defined as region-of-interest (ROI) for FC analysis, the right ITG exhibited increased connectivity with the right precentral gyrus. In addition, the right MFG demonstrated decreased connectivity with both the bilateral anterior cingulate cortex (ACC) and the left precentral gyrus.
Conclusions: By combining ReHo, fALFF, and FC analyses, our work indicated that acute tinnitus patients with hearing loss had abnormal intraregional neural activity and disrupted connectivity in several brain regions which mainly involving the non-auditory area, and these regions are major components of default mode network(DMN), attention network, visual network and executive control network. These findings will help us enhance the understanding of the neuroimaging mechanism in tinnitus populations. Moreover, these abnormalities remind us that we should focus on the early stages of this hearing disease.

Source: https://www.frontiersin.org/articles/10.3389/fnins.2019.01010/abstract

 

[Frédéric]

I remember (back to may 2013), when I had a fMRI in the tinnitus clinic nearby my home, the neurologist told me "you have an hyperactivity in your auditory cortex" but he refused to give this statement "It is tinnitus-related", because there was not enough data and studies done in the world to affirm this assumption. Now it's written below.

Tinnitus and the Brain: A Review of Functional and Anatomical Magnetic Resonance Imaging Studies
Somayeh Shahsavarani
Rafay Ali Khan
Fatima Tazeena Husain
https://doi.org/10.1044/2019_PERS-SIG6-2019-0001

Abstract

Purpose
The tinnitus patient population is inherently heterogeneous. Although tinnitus often co-occurs with hearing loss and is more frequent among elderly people, it affects all age groups with varying hearing sensitivity. In addition, tinnitus severity and patients' reaction to tinnitus vary across individuals. Regardless of the metrics used to measure tinnitus handicap, on one end of the severity spectrum are the patients who have managed to habituate to their tinnitus; at the other end are those who are extremely bothered by tinnitus, and often have a confluence of related comorbidities of mood disorders. Understanding the neural correlates of tinnitus while accounting for such variations could benefit clinicians, helping them modify and objectively monitor tinnitus management strategies. Brain imaging, specifically magnetic resonance imaging, is an excellent tool to study the functional and structural properties of the neural networks involved in tinnitus and tinnitus severity.


Method
In this article, we review studies that employ magnetic resonance imaging-based neuroimaging techniques including resting-state functional connectivity, voxel-based morphometry, and diffusion tensor imaging to investigate underlying functional and structural neural correlates of tinnitus to address overarching dimensions of a person's reaction to tinnitus, namely, audition, emotion, and attention.


Results
We discuss findings from brain imaging studies in the context of theories and models proposed for tinnitus generation and persistence.


Conclusion
These studies have revealed tinnitus-related alteration in the auditory, emotion, and attention neural networks. Future research is required to better understand these changes in the neural circuitry based on tinnitus comorbidities and severity, and to refine existing theoretical models.

 

[Frédéric]

It's quite different from the subject of this thread since it's about spontaneous otoacousic emission.

The pitch of synchronized spontaneous otoacoustic emission does not sound familiar to ears that emit it.

 

[JohnAdams]

How can they use fMRI to measure tinnitus when it is loud and would light up the auditory system? Wouldn't you need perfect silence?

 

[MattS]

How can they use fMRI to measure tinnitus when it is loud and would light up the auditory system? Wouldn't you need perfect silence?

They use a subtraction method John: the sound in the MRI is constant, and so they devise two conditions, one with and one without the tinnitus-relevant stimulus. And then they subtract one from the other. Since the MRI sound is technically a constant within both conditions, the theory is it subtracts to zero, and what you are left with is the tinnitus-specific brain response.

This is actually how all MRI research works, since the MRI environment influences brain activity in all studies, not just sound-related studies.

 

[MattS]

Questions:

How many members are reading Frederik's posted abstracts?

How many people feel they are understanding Frederic's posted abstracts?

Would people appreciate ELI5 summaries/interpretations? Or is it unnecessary? I've started providing them in the tDCS thread, but could do so here as well, if people thought it would be helpful. No point creating make work projects though - so only if enough people think it would be helpful.

 

[Frédéric]

Maladaptive alterations of resting state cortical network in Tinnitus: A directed functional connectivity analysis of a larger MEG data set

Abstract
The present study used resting state MEG whole-head recordings to identify how chronic tonal tinnitus relates to altered functional connectivity of brain's intrinsic cortical networks. Resting state MEG activity of 40 chronic tinnitus patients and 40 matched human controls was compared identifying significant alterations in intrinsic networks of the tinnitus population. Directed functional connectivity of the resting brain, at a whole cortex level, was estimated by means of a statistical comparison of the estimated phase Transfer Entropy (pTE) between the time-series of cortical activations, as reconstructed by LORETA. As pTE identifies the direction of the information flow, a detailed analysis of the connectivity differences between tinnitus patients and controls was possible. Results indicate that the group of tinnitus patients show increased connectivity from right dorsal prefrontal to right medial temporal areas. Our results go beyond previous findings by indicating that the role of the left para-hippocampal area is dictated by a modulation from dmPFC; a region that is part of the dorsal attention network (DAN), as well as implicated in the regulation of emotional processing. Additionally, this whole cortex analysis showed a crucial role of the left inferior parietal cortex, which modulated the activity of the right superior temporal gyrus, providing new hypotheses for the role of this area within the context of current tinnitus models. Overall, these maladaptive alterations of the structure of intrinsic cortical networks show a decrease in efficiency and small worldness of the resting state network of tinnitus patients, which is correlated to tinnitus distress.

Full article: https://www.nature.com/articles/s41598-019-51747-z

 

[Frédéric]

Tinnitus and event related potentials: a systematic review

Abstract

Introduction: Tinnitus is sound perception in the absence of a sound source. Changes in parameters of latency and amplitude on the auditory event related potentials or long latency potentials waves have been cited in tinnitus patients when compared to a control group.

Objective: To perform an assessment of scientific evidence that verifies the possibility of alterations in latency or amplitude of the waves of event related potentials in individuals with tinnitus.

Methods: By using SciELO, Lilacs, ISI Web and PubMed, scientific databases, a review was performed. Articles published in English, Portuguese, French and Spanish that correlated tinnitus with changes in event related potentials were included in this review.

Results: Twelve articles were located, however only eight fulfilled the criteria for inclusion.

Conclusion: The sample of selected studies demonstrate that the long latency auditory evoked potentials related to events between the control and tinnitus patients showed some changes in latency and or amplitude in tinnitus patients. There are changes in event-related potentials when comparing patients with tinnitus and the control group. These changes take place considering the severity of tinnitus, tinnitus site of lesion, and capacity for changes after interventions. The event related potentials can help to determine the neurotransmitter involved in tinnitus generation and evaluate tinnitus treatments.

Full article: see attached file

 

[Frédéric]

Tinnitus Correlates with Downregulation of Cortical Glutamate Decarboxylase 65 Expression but not Auditory Cortical Map Reorganization

Hearing loss is the biggest risk factor for tinnitus and hearing loss-related pathological changes in the auditory pathway have been hypothesized as the mechanism underlying tinnitus. However, due to the comorbidity of tinnitus and hearing loss, it has been difficult to differentiate between neural correlates of tinnitus and consequences of hearing loss. In this study, we dissociated tinnitus and hearing loss in FVB mice, which exhibit robust resistance to tinnitus following monaural noise-induced hearing loss. Furthermore, knockdown of glutamate decarboxylase 65 (GAD65) expression in auditory cortex by RNA interference gave rise to tinnitus in normal-hearing FVB mice. We found that tinnitus was significantly correlated with down-regulation of GAD65 in the auditory cortex. By contrast, cortical map distortions, which have been hypothesized as a mechanism underlying tinnitus, were correlated with hearing loss but not tinnitus. Our findings suggest new strategies for the rehabilitation of tinnitus and other phantom sensation, such as phantom pain.

SIGNIFICANCE STATEMENT

Hearing loss is the biggest risk factor for tinnitus in humans. Most animal models of tinnitus also exhibit comorbid hearing loss, making it difficult to dissociate the mechanisms underlying tinnitus from mere consequences of hearing loss. Here we show that, although both C57BL/6 and FVB mice exhibited similar noise-induced hearing threshold increase, only C57BL/6, but not FVB, mice developed tinnitus following noise exposure. Although both strains showed frequency map reorganization following noise-induced hearing loss, only C57BL/6 mice had reduced GAD65 expression in the auditory cortex. Knocking down GAD65 expression in the auditory cortex resulted in tinnitus in normal hearing FVB mice. Our results suggest that reduced inhibitory neuronal function, but not sensory map reorganization, underlies noise-induced tinnitus.

Source: https://www.jneurosci.org/content/early/2019/11/08/JNEUROSCI.1117-19.2019.abstract

 

[MattS]

Tinnitus Correlates with Downregulation of Cortical Glutamate Decarboxylase 65 Expression but not Auditory Cortical Map Reorganization

Hearing loss is the biggest risk factor for tinnitus and hearing loss-related pathological changes in the auditory pathway have been hypothesized as the mechanism underlying tinnitus. However, due to the comorbidity of tinnitus and hearing loss, it has been difficult to differentiate between neural correlates of tinnitus and consequences of hearing loss. In this study, we dissociated tinnitus and hearing loss in FVB mice, which exhibit robust resistance to tinnitus following monaural noise-induced hearing loss. Furthermore, knockdown of glutamate decarboxylase 65 (GAD65) expression in auditory cortex by RNA interference gave rise to tinnitus in normal-hearing FVB mice. We found that tinnitus was significantly correlated with down-regulation of GAD65 in the auditory cortex. By contrast, cortical map distortions, which have been hypothesized as a mechanism underlying tinnitus, were correlated with hearing loss but not tinnitus. Our findings suggest new strategies for the rehabilitation of tinnitus and other phantom sensation, such as phantom pain.

SIGNIFICANCE STATEMENT

Hearing loss is the biggest risk factor for tinnitus in humans. Most animal models of tinnitus also exhibit comorbid hearing loss, making it difficult to dissociate the mechanisms underlying tinnitus from mere consequences of hearing loss. Here we show that, although both C57BL/6 and FVB mice exhibited similar noise-induced hearing threshold increase, only C57BL/6, but not FVB, mice developed tinnitus following noise exposure. Although both strains showed frequency map reorganization following noise-induced hearing loss, only C57BL/6 mice had reduced GAD65 expression in the auditory cortex. Knocking down GAD65 expression in the auditory cortex resulted in tinnitus in normal hearing FVB mice. Our results suggest that reduced inhibitory neuronal function, but not sensory map reorganization, underlies noise-induced tinnitus.

Source: https://www.jneurosci.org/content/early/2019/11/08/JNEUROSCI.1117-19.2019.abstract

ELI5: This study, conducted in rats, suggests that there is a specific inhibitory process that goes awry in tinnitus. The details of the exact process are complicated and unnecessary to understand at present. But this suggests that the problem isn't the creation of phantom noises, but rather the lack of inhibition of regular bodily noise/functions. Perhaps methods for regaining inhibitory processes would provide treatment opportunities. But, of course, this is in rats - so we are a decade away, even if this is correct.

 

[Frédéric]

Real-time monitoring and regulating auditory cortex alpha activity in patients with chronic tinnitus

Abstract

Objective. Low levels of alpha activity (8-13Hz) mirror a state of enhanced responsiveness, whereas high levels of alpha are a state of reduced responsiveness. Tinnitus is accompanied by reduction of alpha activity in the perisylvian regions compared to normal hearing controls. This reduction might be a key mechanism in the chain of reactions leading to tinnitus. We devised a novel spatial filter as an on-line source monitoring method, which can be used to control alpha activity in the primary auditory cortex. In addition, we designed an innovative experimental procedure to enable suppression of visual and somatosensory alpha, facilitating auditory alpha control during alpha neurofeedback.

Approach. An amplitude-modulated auditory stimulation with 40 Hz modulation frequency and 1000 Hz carrier frequency specifically activates the primary auditory cortex. The topography of 40 Hz oscillations depicts the activity of the auditory cortices. We used this map as a spatial filter, which passes the activity originating from the auditory cortex. To suppress superposition of auditory alpha by somatosensory and visual alpha, we used a continuous tactile jaw-stimulation and visual stimulation protocol to suppress somatosensory alpha of regions adjacent to the auditory cortex and visual alpha for local regulation of auditory alpha activity only.

Main results. This novel spatial filter for online detection auditory alpha EEG-activity and the usage of multi-sensory stimulation facilities the appearance of alpha activity from the auditory cortex at the sensor level.

Significance. The proposed procedure can be used in an EEG-neurofeedback-treatment approach allowing online auditory alpha self-regulation training in patients with chronic tinnitus.

Source: https://iopscience.iop.org/article/10.1088/1741-2552/ab57d5/meta

 

[Frédéric]

Chronic tinnitus exhibits bidirectional functional dysconnectivity in frontostriatal circuit

Purpose: The phantom sound of tinnitus is considered to be associated with abnormal functional coupling between the nucleus accumbens (NAc) and the prefrontal cortex, which may form a frontostriatal top-down gating system to evaluate and modulate sensory signals. Resting-state functional magnetic resonance imaging (fMRI) was used to recognize the aberrant directional connectivity of the NAc in chronic tinnitus and to ascertain the relationship between this connectivity and tinnitus characteristics.

Methods: Participants included chronic tinnitus patients (n=50) and healthy controls (n=55), matched for age, sex, education, and hearing thresholds. The hearing status of both groups was comparable. On the basis of the NAc as a seed region, a Granger causality analysis study was conducted to investigate the directional connectivity and the relationship with tinnitus duration or distress.

Results: Compared to healthy controls, tinnitus patients exhibited abnormal directional connectivity between the NAc and the prefrontal cortex, principally the middle frontal gyrus (MFG), orbitofrontal cortex (OFC), and inferior frontal gyrus (IFG). Additionally, positive correlations between Tinnitus Handicap Questionnaire (THQ) scores and increased directional connectivity from the right NAc to the left MFG (r=0.357, p=0.015) and from the right MFG to the left NAc (r=0.626, p<0.001) were observed. Furthermore, the enhanced directional connectivity from the right NAc to the right OFC was positively associated with the duration of tinnitus (r=0.599, p<0.001).

Conclusions: Concurring with expectations, tinnitus distress was correlated with enhanced directional connectivity between the NAc and the prefrontal cortex. The current study not only helps illuminate the neural basis of the frontostriatal gating control of tinnitus sensation but also contribute to deciphering the neuropathological features of tinnitus.

Source: https://www.frontiersin.org/articles/10.3389/fnins.2019.01299/abstract

 

[Frédéric]

The Cortisol Awakening Response (CAR) – A feasibility study investigating the use of the Area Under the Curve with Respect to Increase (AUCi) as an effective objective measure of tinnitus distress.

 

[Daniel Lion]

Chronic tinnitus exhibits bidirectional functional dysconnectivity in frontostriatal circuit

Purpose: The phantom sound of tinnitus is considered to be associated with abnormal functional coupling between the nucleus accumbens (NAc) and the prefrontal cortex, which may form a frontostriatal top-down gating system to evaluate and modulate sensory signals. Resting-state functional magnetic resonance imaging (fMRI) was used to recognize the aberrant directional connectivity of the NAc in chronic tinnitus and to ascertain the relationship between this connectivity and tinnitus characteristics.

Methods: Participants included chronic tinnitus patients (n=50) and healthy controls (n=55), matched for age, sex, education, and hearing thresholds. The hearing status of both groups was comparable. On the basis of the NAc as a seed region, a Granger causality analysis study was conducted to investigate the directional connectivity and the relationship with tinnitus duration or distress.

Results: Compared to healthy controls, tinnitus patients exhibited abnormal directional connectivity between the NAc and the prefrontal cortex, principally the middle frontal gyrus (MFG), orbitofrontal cortex (OFC), and inferior frontal gyrus (IFG). Additionally, positive correlations between Tinnitus Handicap Questionnaire (THQ) scores and increased directional connectivity from the right NAc to the left MFG (r=0.357, p=0.015) and from the right MFG to the left NAc (r=0.626, p<0.001) were observed. Furthermore, the enhanced directional connectivity from the right NAc to the right OFC was positively associated with the duration of tinnitus (r=0.599, p<0.001).

Conclusions: Concurring with expectations, tinnitus distress was correlated with enhanced directional connectivity between the NAc and the prefrontal cortex. The current study not only helps illuminate the neural basis of the frontostriatal gating control of tinnitus sensation but also contribute to deciphering the neuropathological features of tinnitus.

Source: https://www.frontiersin.org/articles/10.3389/fnins.2019.01299/abstract

@MattS, help decipher this please if you have time. Any of Frederic's above posts, but this one in particular looked quite meaty.

Cheers.

 

[Frédéric]

Abnormal spontaneous neural activity of the central auditory system reflects altered functional connectivity in the tinnitus brain: A resting-state fMRI study

Objective: An abnormal state of the central auditory system (CAS) likely plays a large role in the occurrence of phantom sound of tinnitus. Various tinnitus studies using resting-state functional magnetic resonance imaging (RS-fMRI) have reported aberrant spontaneous brain activity in the non-auditory system (NAS) and altered functional connectivity between the CAS and NAS. This study aimed to investigate abnormal functional connections between the aberrant spontaneous activity in the CAS and the whole brain in tinnitus patients, compared to healthy controls (HC) using RS-fMRI

Materials and methods: RS-fMRI from 16 right-ear TNH and 15 HC individuals was collected, and the time series were extracted from different clusters of a CAS template, supplied by the Anatomy Toolbox of the Statistical Parametric Mapping software. These data were used to derive the smoothed mean amplitude of low-frequency fluctuation (smALFF) values and calculate the relationship between such values and the corresponding clinical data. Additionally, clusters in the CAS identified by the smALFF maps were set as seed regions for calculating and comparing the brain-wide connectivity between TNH and HC.

Results: We identified the different clusters located in the left Higher Auditory Cortex (HAC) and the right inferior colliculus (IC) from the smALFF maps that contained increased (HAC) and decreased (IC) activity when the TNH group compared to the HC group, respectively. The value of increased smALFF cluster in the HAC was positively correlated with the tinnitus score, but the decreased smALFF cluster in the IC was not correlated with any clinical characters of tinnitus. The TNH group displayed increased connectivity, compared to the HC group, in brain regions that encompassed the left IC, bilateral Heschl gyrus, bilateral supplementary motor area, right insula, bilateral superior temporal gyrus, right middle temporal gyrus, left hippocampus, left amygdala and right supramarginal gyrus.

Conclusion: Tinnitus may be linked to abnormal spontaneous activity in the HAC, which can arise from the neural plasticity induced from the increased functional connectivity between the auditory network, cerebellum and limbic system.

Source: https://www.frontiersin.org/articles/10.3389/fnins.2019.01314/abstract

 

[MattS]

Maladaptive alterations of resting state cortical network in Tinnitus: A directed functional connectivity analysis of a larger MEG data set

Abstract
The present study used resting state MEG whole-head recordings to identify how chronic tonal tinnitus relates to altered functional connectivity of brain's intrinsic cortical networks. Resting state MEG activity of 40 chronic tinnitus patients and 40 matched human controls was compared identifying significant alterations in intrinsic networks of the tinnitus population. Directed functional connectivity of the resting brain, at a whole cortex level, was estimated by means of a statistical comparison of the estimated phase Transfer Entropy (pTE) between the time-series of cortical activations, as reconstructed by LORETA. As pTE identifies the direction of the information flow, a detailed analysis of the connectivity differences between tinnitus patients and controls was possible. Results indicate that the group of tinnitus patients show increased connectivity from right dorsal prefrontal to right medial temporal areas. Our results go beyond previous findings by indicating that the role of the left para-hippocampal area is dictated by a modulation from dmPFC; a region that is part of the dorsal attention network (DAN), as well as implicated in the regulation of emotional processing. Additionally, this whole cortex analysis showed a crucial role of the left inferior parietal cortex, which modulated the activity of the right superior temporal gyrus, providing new hypotheses for the role of this area within the context of current tinnitus models. Overall, these maladaptive alterations of the structure of intrinsic cortical networks show a decrease in efficiency and small worldness of the resting state network of tinnitus patients, which is correlated to tinnitus distress.

Full article: https://www.nature.com/articles/s41598-019-51747-z

ELI5: This study measured the "functional connectivity" of the brain's "resting-state networks" in 40 tinnitus and 40 non-tinnitus participants. By "functional connectivity", they mean "brain regions that activate/deactivate in relative synchrony". And by "resting-state" they mean the brain while the participant is just asked to lay still and not otherwise do much. These resting-state networks are super popular research topics these days, and are believed to relate to the brain's underlying structure and background activity levels. Anyway, this study measured them in tinnitus/non-tinnitus patients and found that there was increased connectivity, but perhaps decreased organization, in the tinnitus patient's brain. The increased connectivity was in regions the authors claim relate to emotional and attentional networks (which isn't false, but may be a bit simplistic), which makes sense for reasons that should be obvious. So, bottom line: the study gels with work suggesting overactive attention/emotion networks in tinnitus patients. It's good work; but probably a good distance from anything that would have treatment implications.

 

[MattS]

Chronic tinnitus exhibits bidirectional functional dysconnectivity in frontostriatal circuit

Purpose: The phantom sound of tinnitus is considered to be associated with abnormal functional coupling between the nucleus accumbens (NAc) and the prefrontal cortex, which may form a frontostriatal top-down gating system to evaluate and modulate sensory signals. Resting-state functional magnetic resonance imaging (fMRI) was used to recognize the aberrant directional connectivity of the NAc in chronic tinnitus and to ascertain the relationship between this connectivity and tinnitus characteristics.

Methods: Participants included chronic tinnitus patients (n=50) and healthy controls (n=55), matched for age, sex, education, and hearing thresholds. The hearing status of both groups was comparable. On the basis of the NAc as a seed region, a Granger causality analysis study was conducted to investigate the directional connectivity and the relationship with tinnitus duration or distress.

Results: Compared to healthy controls, tinnitus patients exhibited abnormal directional connectivity between the NAc and the prefrontal cortex, principally the middle frontal gyrus (MFG), orbitofrontal cortex (OFC), and inferior frontal gyrus (IFG). Additionally, positive correlations between Tinnitus Handicap Questionnaire (THQ) scores and increased directional connectivity from the right NAc to the left MFG (r=0.357, p=0.015) and from the right MFG to the left NAc (r=0.626, p<0.001) were observed. Furthermore, the enhanced directional connectivity from the right NAc to the right OFC was positively associated with the duration of tinnitus (r=0.599, p<0.001).

Conclusions: Concurring with expectations, tinnitus distress was correlated with enhanced directional connectivity between the NAc and the prefrontal cortex. The current study not only helps illuminate the neural basis of the frontostriatal gating control of tinnitus sensation but also contribute to deciphering the neuropathological features of tinnitus.

Source: https://www.frontiersin.org/articles/10.3389/fnins.2019.01299/abstract

@Daniel Lion

ELI5: This paper is actually hot off the press, and only exists in abstract form at the moment. So I can only go by what's in the abstract. According to that, this is another study to investigate resting state connectivity, but unlike the other study, it zoned right in on a connection between the nucleus accumbens (a small brain structure with known involvement in reward/punishment/motivation/habit learning) and the prefrontal cortex (involved in decision making/thinking/reasoning). They found *increased* connecticity, in both directions (but mostly prefrontal to NAc), in the tinnitus patients compared to controls. It's unclear exactly what this may mean, but the authors hint at a "frontostriatal gating" hypothesis, which I take to mean that they believe these connections may be involved in the control of which brain signals do and don't get passed on to other brain regions (ie. are 'gated'). This is plausible, but I'm not sure what the exact relevance to tinnitus would be...would have to wait for the full paper to come out to see exactly what the authors are thinking.

 

[MattS]

Abnormal spontaneous neural activity of the central auditory system reflects altered functional connectivity in the tinnitus brain: A resting-state fMRI study

Objective: An abnormal state of the central auditory system (CAS) likely plays a large role in the occurrence of phantom sound of tinnitus. Various tinnitus studies using resting-state functional magnetic resonance imaging (RS-fMRI) have reported aberrant spontaneous brain activity in the non-auditory system (NAS) and altered functional connectivity between the CAS and NAS. This study aimed to investigate abnormal functional connections between the aberrant spontaneous activity in the CAS and the whole brain in tinnitus patients, compared to healthy controls (HC) using RS-fMRI

Materials and methods: RS-fMRI from 16 right-ear TNH and 15 HC individuals was collected, and the time series were extracted from different clusters of a CAS template, supplied by the Anatomy Toolbox of the Statistical Parametric Mapping software. These data were used to derive the smoothed mean amplitude of low-frequency fluctuation (smALFF) values and calculate the relationship between such values and the corresponding clinical data. Additionally, clusters in the CAS identified by the smALFF maps were set as seed regions for calculating and comparing the brain-wide connectivity between TNH and HC.

Results: We identified the different clusters located in the left Higher Auditory Cortex (HAC) and the right inferior colliculus (IC) from the smALFF maps that contained increased (HAC) and decreased (IC) activity when the TNH group compared to the HC group, respectively. The value of increased smALFF cluster in the HAC was positively correlated with the tinnitus score, but the decreased smALFF cluster in the IC was not correlated with any clinical characters of tinnitus. The TNH group displayed increased connectivity, compared to the HC group, in brain regions that encompassed the left IC, bilateral Heschl gyrus, bilateral supplementary motor area, right insula, bilateral superior temporal gyrus, right middle temporal gyrus, left hippocampus, left amygdala and right supramarginal gyrus.

Conclusion: Tinnitus may be linked to abnormal spontaneous activity in the HAC, which can arise from the neural plasticity induced from the increased functional connectivity between the auditory network, cerebellum and limbic system.

Source: https://www.frontiersin.org/articles/10.3389/fnins.2019.01314/abstract

ELI5: Another resting-state study. This one has calculated a measure of 'signal frequency' within the resting state brain activity of the auditory cortex (that's smALFF), identified regions where smALFF differed between (a small sample of) tinnitus patients and controls, and measured connectivity of these regions with other areas of the brain. What they found was that smALFF levels in the higher auditory cortex correlated with a 'tinnitus score', and [unsurprisingly], connectivity of the higher auditory cortex to many other brain regions was higher in Tinnitus patients.

Take-home message: One possibility is that this smALFF measure may serve as a marker of tinnitus severity. This is possible, particular since it's focused on auditory cortex activity in particular. However, sample size was very small, and smALFF is a quite common and quite generic metric used in many areas of research, so the likelihood it provides a really sensitive and specific metric of tinnitus seems low to me.

 

[MattS]

Real-time monitoring and regulating auditory cortex alpha activity in patients with chronic tinnitus

Abstract

Objective. Low levels of alpha activity (8-13Hz) mirror a state of enhanced responsiveness, whereas high levels of alpha are a state of reduced responsiveness. Tinnitus is accompanied by reduction of alpha activity in the perisylvian regions compared to normal hearing controls. This reduction might be a key mechanism in the chain of reactions leading to tinnitus. We devised a novel spatial filter as an on-line source monitoring method, which can be used to control alpha activity in the primary auditory cortex. In addition, we designed an innovative experimental procedure to enable suppression of visual and somatosensory alpha, facilitating auditory alpha control during alpha neurofeedback.

Approach. An amplitude-modulated auditory stimulation with 40 Hz modulation frequency and 1000 Hz carrier frequency specifically activates the primary auditory cortex. The topography of 40 Hz oscillations depicts the activity of the auditory cortices. We used this map as a spatial filter, which passes the activity originating from the auditory cortex. To suppress superposition of auditory alpha by somatosensory and visual alpha, we used a continuous tactile jaw-stimulation and visual stimulation protocol to suppress somatosensory alpha of regions adjacent to the auditory cortex and visual alpha for local regulation of auditory alpha activity only.

Main results. This novel spatial filter for online detection auditory alpha EEG-activity and the usage of multi-sensory stimulation facilities the appearance of alpha activity from the auditory cortex at the sensor level.

Significance. The proposed procedure can be used in an EEG-neurofeedback-treatment approach allowing online auditory alpha self-regulation training in patients with chronic tinnitus.

Source: https://iopscience.iop.org/article/10.1088/1741-2552/ab57d5/meta

ELI5: The title sounds super exciting, but this study looks to have run *zero* tinnitus patients. What they have done is designed a system that could be used to undertake a neurofeedback protocol, where people are provided with real-time information about a specific feature of their brain state (in this case alpha waves), and attempt to use that information to guide increases and decreases of this neural feature. I've actually done a bit of this neurofeedback work - and there is evidence that people *can* regulate their brain activity in certain ways. Whether regulation of alpha waves can help tinnitus waits to be seen (and was not tested here).

 

[Daniel Lion]

Thank you @MattS for deciphering these documents and giving feedback.

Much appreciated... well done sir.

 

[Frédéric]

Tinnitus and event related potentials: a systematic review

 

[JohnAdams]

Tinnitus and event related potentials: a systematic review

Even the first sentence of this paper says it; Tinnitus is a perception of sound in absence of a sound source.

So, how can people like the ESIT correlate emotional recovery with "tinnitus improvement" when their measure has nothing to do with decreasing the perception of the sound?