Frontostriatal Gating of Tinnitus and Chronic Pain

doi:10.1016/j.tics.2015.08.002

Trends in Cognitive Sciences

Volume 19, Issue 10, October 2015, Pages 567-578

https://doi.org/10.1016/j.tics.2015.08.002 Get rights and content

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Ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAc) in the ventral striatum form a frontostriatal gating system for the valuation and top-down modulation of sensory signals.

A reduction in grey matter volume of medial prefrontal cortex, as determined with voxel-based morphometry, is one of the signature biomarkers of both tinnitus and chronic pain, although the exact location varies.

Different subregions of the subcallosal region control tinnitus intensity and tinnitus distress: vmPFC is part of a gain control circuit; the subcallosal anterior cingulate cortex is responsible for negative valuation.

Dopamine and serotonin act as neuromodulators of frontostriatal activity in chronic pain, and this may provide avenues for future treatment of both disorders.

Tinnitus and chronic pain are sensory–perceptual disorders associated with negative affect and high impact on well-being and behavior. It is now becoming increasingly clear that higher cognitive and affective brain systems are centrally involved in the pathology of both disorders. We propose that the ventromedial prefrontal cortex and the nucleus accumbens are part of a central ‘gatekeeping’ system in both sensory modalities, a system which evaluates the relevance and affective value of sensory stimuli and controls information flow via descending pathways. If this frontostriatal system is compromised, long-lasting disturbances are the result. Parallels in both systems are striking and mutually informative, and progress in understanding central gating mechanisms might provide a new impetus to the therapy of tinnitus and chronic pain.

Section snippets

Brain Structure and Function in Tinnitus and Chronic Pain

Neuroimaging and neurophysiological studies have revealed extensive changes of brain structure and function in tinnitus and chronic pain, as shown by altered measures of grey and white matter as well as local and network activity. Figure 1 illustrates how remarkably-similar structures are involved in both disorders.

Mechanisms of Frontostriatal Gating

Converging lines of evidence, as outlined above, indicate that tinnitus and chronic pain are associated with structural and functional brain changes that overlap remarkably between the two conditions (Figure 1). The changes predominantly affect frontostriatal circuits including vmPFC and NAc, with possible additional roles for the thalamus and for medial temporal lobe structures, such as amygdala and hippocampus. Frontostriatal circuits with their closed-loop structure are anatomically

Neurotransmitter Systems Involved in Frontostriatal Gating

Figure 3 demonstrates that the frontostriatal gating and valuation process is under the control of two major transmitter systems: dopamine and serotonin.

Decreasing dopamine activity seems to reduce tinnitus perception [111]. Furthermore, serotonin has long been hypothesized to play a role in tinnitus and in its comorbidity with depression and insomnia 112, 113. In addition, the proposed loss of inhibition in tinnitus has been suggested to be due to lowered γ-amino butyric acid (GABA) levels

Concluding Remarks and Clinical Implications

As discussed in this review, a central and causal role of frontostriatal circuits for the development and maintenance of tinnitus and chronic pain is emerging. We specifically propose that the ventromedial prefrontal cortex and the nucleus accumbens are part of a central ‘gatekeeping’ system, which evaluates the relevance and affective value of sensory stimuli and controls information flow via descending pathways.

Having identified the frontostriatal gating system as crucial for the development

Acknowledgments

Tinnitus research in the laboratory of J.P.R. has been supported by the National Institutes of Health (RC1-DC010720), the American Tinnitus Association, the Skirball Foundation, the Tinnitus Research Initiative, and the Tinnitus Research Consortium. A.M. is funded by the Belgian American Educational Foundation (BAEF). The work of E.S.M. and M.P. is funded by the Deutsche Forschungsgemeinschaft (PL 321/10-1, PL 321/11-1).

Glossary

Allodynia: pain due to a stimulus that does not normally provoke pain.
Chronic pain: pain that persists past healing time, lasts or recurs for more than 3–6 months, and lacks the warning function of acute pain.
Hyperacusis: decreased tolerance or heightened sensitivity to specific sound frequencies beyond a particular volume. Can lead to a painful or troublesome sensation with sounds that would not trouble a normal individual.
Hyperalgesia: increased pain from a stimulus that normally provokes pain.

References (153)

R.L. Folmer
Chronic tinnitus as phantom auditory pain
Otolaryngol. Head Neck Surg.
(2001)
J. Tonndorf
The analogy between tinnitus and pain: a suggestion for a physiological basis of chronic tinnitus
Hear. Res.
(1987)
A.A. Vendrig
The Minnesota Multiphasic Personality Inventory and chronic pain: a conceptual analysis of a long-standing but complicated relationship
Clin. Psychol. Rev.
(2000)
A.V. Apkarian
Towards a theory of chronic pain
Prog. Neurobiol.
(2009)
J.E. Isaacson
Clinical associations between tinnitus and chronic pain
Otolaryngol. Head Neck Surg.
(2003)
A.M. Leaver
Dysregulation of limbic and auditory networks in tinnitus
Neuron
(2011)
J.P. Rauschecker
Tuning out the noise: limbic-auditory interactions in tinnitus
Neuron
(2010)
M. Landgrebe
Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas
Neuroimage
(2009)
P. Adjamian
Neuroanatomical abnormalities in chronic tinnitus in the human brain
Neurosci. Biobehav. Rev.
(2014)
K. Boyen
Gray matter in the brain: differences associated with tinnitus and hearing loss
Hear. Res.
(2013)

P. Schneider

Reduced volume of Heschl's gyrus in tinnitus

Neuroimage

(2009)

R.F. Smallwood

Structural brain anomalies and chronic pain: a quantitative meta-analysis of gray matter volume

J. Pain

(2013)

F. Cauda

Gray matter alterations in chronic pain: a network-oriented meta-analytic approach

Neuroimage Clin.

(2014)

Y.J. Lee

Evaluation of white matter structures in patients with tinnitus using diffusion tensor imaging

J. Clin. Neurosci.

(2007)

F.T. Husain

Neuroanatomical changes due to hearing loss and chronic tinnitus: a combined VBM and DTI study

Brain Res.

(2011)

R.R. Benson

Left hemisphere fractional anisotropy increase in noise-induced tinnitus: a diffusion tensor imaging (DTI) study of white matter tracts in the brain

Hear. Res.

(2014)

P.Y. Geha

The brain in chronic CRPS pain: abnormal gray–white matter interactions in emotional and autonomic regions

Neuron

(2008)

S.A. Khan

Altered structure and function in the hippocampus and medial prefrontal cortex in patients with burning mouth syndrome

Pain

(2014)

A.R. Mansour

Brain white matter structural properties predict transition to chronic pain

Pain

(2013)

S.A. Reyes

Brain imaging of the effects of lidocaine on tinnitus

Hear. Res.

(2002)

J.R. Melcher

The auditory midbrain of people with tinnitus: abnormal sound-evoked activity revisited

Hear. Res.

(2009)

C.P. Lanting

Neural correlates of human somatosensory integration in tinnitus

Hear. Res.

(2010)

J.P. Rauschecker

Auditory cortical plasticity: a comparison with other sensory systems

Trends Neurosci.

(1999)

V. Di Piero

Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy

Pain

(1991)

J.C. Hsieh

Central representation of chronic ongoing neuropathic pain studied by positron emission tomography

Pain

(1995)

M.J. Iadarola

Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain

Pain

(1995)

C.H. Tu

Abnormal cerebral metabolism during menstrual pain in primary dysmenorrhea

Neuroimage

(2009)

J. Liu

Quantitative cerebral blood flow mapping and functional connectivity of postherpetic neuralgia pain: a perfusion fMRI study

Pain

(2013)

L. Becerra

Reward circuitry activation by noxious thermal stimuli

Neuron

(2001)

J. Stern

Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients

Neuroimage

(2006)

A. Maudoux

Connectivity graph analysis of the auditory resting state network in tinnitus

Brain Res.

(2012)

F. Grabenhorst et al.

Value, pleasure and choice in the ventral prefrontal cortex

Trends Cogn. Sci.

(2011)

M. Roy

Ventromedial prefrontal–subcortical systems and the generation of affective meaning

Trends Cogn. Sci.

(2012)

D. De Ridder

The Bayesian brain: phantom percepts resolve sensory uncertainty

Neurosci. Biobehav. Rev.

(2014)

C.A. Bauer

The cerebellum as a novel tinnitus generator

Hear. Res.

(2013)

E.A. Moulton

The cerebellum and pain: passive integrator or active participator?

Brain Res. Rev.

(2010)

G.J. Macfarlane

Epidemiology of pain

J.J. Eggermont et al.

The neuroscience of tinnitus: understanding abnormal and normal auditory perception

Front. Syst. Neurosci.

(2012)

H. Breivik

The individual and societal burden of chronic pain in Europe: the case for strategic prioritisation and action to improve knowledge and availability of appropriate care

BMC Public Health

(2013)

J.A. Henry

General review of tinnitus: prevalence, mechanisms, effects, and management

J. Speech Lang. Hear. Res.

(2005)

A.R. Møller

Similarities between chronic pain and tinnitus

Am. J. Otol.

(1997)

C. Meric

Psychopathological profile of tinnitus sufferers: evidence concerning the relationship between tinnitus features and impact on life

Audiol. Neurootol.

(1998)

K.M. Holgers

Predictive factors for development of severe tinnitus suffering-further characterisation

Int. J. Audiol.

(2005)

M. Mühlau

Structural brain changes in tinnitus

Cereb. Cortex

(2006)

A.M. Leaver

Cortico-limbic morphology separates tinnitus from tinnitus distress

Front. Syst. Neurosci.

(2012)

F.M. Aldhafeeri

Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging

Neuroradiology

(2012)

S. Vanneste

Tinnitus: a large VBM–EEG correlational study

PLoS ONE

(2015)

A. May

Structural brain imaging: a window into chronic pain

Neuroscientist

(2011)

M.N. Baliki

Brain morphological signatures for chronic pain

PLoS ONE

(2011)

M.N. Baliki

Corticostriatal functional connectivity predicts transition to chronic back pain

Nat. Neurosci.

(2012)

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Acoustic trauma increases inhibitory effects of amygdala electrical stimulation on thalamic neurons in a rat model
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Acoustic trauma (AT) induced hearing loss elicits plasticity throughout the central auditory pathway, including at the level of the medial geniculate nucleus (MGN). Hearing loss also results in altered neuronal responses in the amygdala, which is involved in sensory gating at the level of the MGN. However, whether these altered responses in the amygdala affect sensory gating at the level of the MGN requires further evaluation. The current study aimed to investigate the effects of AT-induced hearing loss on the functional connectivity between the amygdala and the MGN. Male Sprague–Dawley rats were exposed to either sham (n = 5; no sound) or AT (n = 6; 16 kHz, 1 h, 124 dB SPL) under full anaesthesia. Auditory brainstem response (ABR) recordings were made to determine hearing thresholds. Two weeks post-exposure, extracellular recordings were used to assess the effect of electrical stimulation of the amygdala on tone-evoked (sham n = 22; AT n = 30) and spontaneous (sham n = 21; AT n = 29) activity of single neurons in the MGN. AT caused a large temporary and small permanent ABR threshold shift. Electrical stimulation of the amygdala induced differential effects (excitatory, inhibitory, or no effect) on both tone-evoked and spontaneous activity. In tone-evoked activity, electrical stimulation at 300 µA, maximum current, caused a significantly larger reduction in firing rate in AT animals compared to sham, due to an increase in the magnitude of inhibitory effects. In spontaneous activity, there was also a significantly larger magnitude of inhibitory effects following AT. The findings confirm that activation of the amygdala results in changes in MGN neuronal activity, and suggest the functional connectivity between the amygdala and the MGN is significantly altered following AT and subsequent hearing loss.
Sensory gating functions of the auditory thalamus: Adaptation and modulations through noise-exposure and high-frequency stimulation in rats
2023, Behavioural Brain Research
The medial geniculate body (MGB) of the thalamus is an obligatory relay for auditory processing. A breakdown of adaptive filtering and sensory gating at this level may lead to multiple auditory dysfunctions, while high-frequency stimulation (HFS) of the MGB might mitigate aberrant sensory gating. To further investigate the sensory gating functions of the MGB, this study (i) recorded electrophysiological evoked potentials in response to continuous auditory stimulation, and (ii) assessed the effect of MGB HFS on these responses in noise-exposed and control animals. Pure-tone sequences were presented to assess differential sensory gating functions associated with stimulus pitch, grouping (pairing), and temporal regularity. Evoked potentials were recorded from the MGB and acquired before and after HFS (100 Hz). All animals (unexposed and noise-exposed, pre- and post-HFS) showed gating for pitch and grouping. Unexposed animals also showed gating for temporal regularity not found in noise-exposed animals. Moreover, only noise-exposed animals showed restoration comparable to the typical EP amplitude suppression following MGB HFS. The current findings confirm adaptive thalamic sensory gating based on different sound characteristics and provide evidence that temporal regularity affects MGB auditory signaling.
Onset-offset cortical auditory evoked potential amplitude differences indicate auditory cortical hyperactivity and reduced inhibition in people with tinnitus
2023, Clinical Neurophysiology
The current study investigates evidence of hypothesized reduced central inhibition and/or increased excitation in individuals with tinnitus by evaluating cortical auditory onset versus offset responses.
Cortical auditory evoked potentials (CAEPs) were recorded to the onset and offset of 3-second white noise stimuli in tinnitus and control groups matched in pairs by age, hearing, and sex (n = 26 total). Independent t-tests and 2-way mixed model ANOVA were used to evaluate onset-offset differences in amplitude, area, and latency of CAEP components by group. The predictive influence of tinnitus presence and associated participant characteristics on CAEP outcomes was assessed by multiple regression proportional reduction in error.
The tinnitus group had significantly larger onset minus offset P2 amplitudes (ΔP2 amplitudes) than control group participants. No other component variables differed significantly. ΔP2 amplitude was best predicted by tinnitus status and not significantly influenced by other variables such as hearing loss or age.
Hypothesized reduced central inhibition and/or increased excitation in tinnitus participants was partially supported by a group difference in ΔP2 amplitude.
This was the first study to evaluate CAEP onset minus offset differences to investigate changes in central excitation/inhibition in individuals with tinnitus versus controls in matched groups.
Comparing tinnitus, pain, psychosocial and cognitive factors between patients with tinnitus and pain: A systematic review
2023, Journal of Psychosomatic Research
Tinnitus is a multifactorial symptom, which shows similarities with the involved mechanisms in chronic pain. The aim of this systematic review is to provide an overview of studies comparing patients with only tinnitus to patients with pain (headache, temporomandibular joint (TMJ) pain or neck pain) with or without tinnitus, regarding tinnitus-related, pain-related, psychosocial and cognitive factors.
This systematic review was written following the PRISMA guidelines. To identify relevant articles, PubMed, Web of Science and Embase databases were searched. The risk of bias was rated using the Newcastle Ottawa scale for case-control studies.
Ten articles were included in the qualitative analysis. The risk of bias ranged from low to moderate. Low to moderate evidence shows that patients with tinnitus experience higher mean symptom intensity, but lower psychosocial and cognitive distress, compared to patients with pain. Inconsistent results were found for tinnitus-related factors. Low to moderate evidence points to a higher severity of hyperacusis and psychosocial distress in patients with both pain and tinnitus, compared to patients with tinnitus only, as well as for positive associations between tinnitus-related factors and the presence or intensity of pain.
This systematic review shows that psychosocial dysfunctions are more clearly present in patients with pain only, compared to patients with tinnitus only and the co-occurrence of tinnitus and pain increases psychosocial distress as well as hyperacusis severity. Some positive associations were identified between tinnitus-related and pain-related factors.
Functional ear symptoms referred to an otology clinic: incidence, co-morbidity, aetiological factors and a new experience-driven clinical model
2023, Journal of Laryngology and Otology
Genetic architecture distinguishes tinnitus from hearing loss
2024, Nature Communications

View all citing articles on Scopus

^‡: These authors contributed equally to this work.

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Trends in Cognitive Sciences

OpinionFrontostriatal Gating of Tinnitus and Chronic Pain

Trends

Section snippets

Brain Structure and Function in Tinnitus and Chronic Pain

Mechanisms of Frontostriatal Gating

Neurotransmitter Systems Involved in Frontostriatal Gating

Concluding Remarks and Clinical Implications

Acknowledgments

Glossary

Otolaryngol. Head Neck Surg.

Hear. Res.

Clin. Psychol. Rev.

Prog. Neurobiol.

Otolaryngol. Head Neck Surg.

Neuron

Neuron

Neuroimage

Neurosci. Biobehav. Rev.

Hear. Res.

Neuroimage

J. Pain

Neuroimage Clin.

J. Clin. Neurosci.

Brain Res.

Hear. Res.

Neuron

Pain

Pain

Hear. Res.

Hear. Res.

Hear. Res.

Trends Neurosci.

Pain

Pain

Pain

Neuroimage

Pain

Neuron

Neuroimage

Brain Res.

Trends Cogn. Sci.

Trends Cogn. Sci.

Neurosci. Biobehav. Rev.

Hear. Res.

Brain Res. Rev.

Epidemiology of pain

The neuroscience of tinnitus: understanding abnormal and normal auditory perception

Front. Syst. Neurosci.

The individual and societal burden of chronic pain in Europe: the case for strategic prioritisation and action to improve knowledge and availability of appropriate care

BMC Public Health

General review of tinnitus: prevalence, mechanisms, effects, and management

J. Speech Lang. Hear. Res.

Similarities between chronic pain and tinnitus

Am. J. Otol.

Psychopathological profile of tinnitus sufferers: evidence concerning the relationship between tinnitus features and impact on life

Audiol. Neurootol.

Predictive factors for development of severe tinnitus suffering-further characterisation

Int. J. Audiol.

Structural brain changes in tinnitus

Cereb. Cortex

Cortico-limbic morphology separates tinnitus from tinnitus distress

Front. Syst. Neurosci.

Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging

Neuroradiology

Tinnitus: a large VBM–EEG correlational study

PLoS ONE

Structural brain imaging: a window into chronic pain

Neuroscientist

Brain morphological signatures for chronic pain

PLoS ONE

Corticostriatal functional connectivity predicts transition to chronic back pain

Nat. Neurosci.

Opinion
Frontostriatal Gating of Tinnitus and Chronic Pain