Frequency-specific alternations in the amplitude of low-frequency fluctuations in chronic tinnitus

Abstract

Tinnitus, a phantom ringing, buzzing, or hissing sensation with potentially debilitating consequences, is thought to arise from aberrant spontaneous neural activity at one or more sites within the central nervous system; however, the location and specific features of these oscillations are poorly understood with respect to specific tinnitus features. Recent resting-state functional magnetic resonance imaging (fMRI) studies suggest that aberrant fluctuations in spontaneous low-frequency oscillations (LFO) of the blood oxygen level-dependent (BOLD) signal may be an important factor in chronic tinnitus; however, the role that frequency-specific components of LFO play in subjective tinnitus remains unclear. A total of 39 chronic tinnitus patients and 41 well-matched healthy controls participated in the resting-state fMRI scans. The LFO amplitudes were investigated using the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) in two different frequency bands (slow-4: 0.027–0.073 Hz and slow-5: 0.01–0.027 Hz). We observed significant differences between tinnitus patients and normal controls in ALFF/fALFF in the two bands (slow-4 and slow-5) in several brain regions including the superior frontal gyrus (SFG), inferior frontal gyrus, middle temporal gyrus, angular gyrus, supramarginal gyrus, and middle occipital gyrus. Across the entire subject pool, significant differences in ALFF/fALFF between the two bands were found in the midbrain, basal ganglia, hippocampus and cerebellum (Slow 4 > Slow 5), and in the middle frontal gyrus, supramarginal gyrus, posterior cingulate cortex, and precuneus (Slow 5 > Slow 4). We also observed significant interaction between frequency bands and patient groups in the orbitofrontal gyrus. Furthermore, tinnitus distress was positively correlated with the magnitude of ALFF in right SFG and the magnitude of fALFF slow-4 band in left SFG, whereas tinnitus duration was positively correlated with the magnitude of ALFF in right SFG and the magnitude of fALFF slow-5 band in left SFG. Resting-state fMRI provides an unbiased method for identifying aberrant spontaneous LFO occurring throughout the central nervous system. Chronic tinnitus patients have widespread abnormalities in ALFF and fALFF slow-4 and slow-5 band which are correlated with tinnitus distress and duration. These results provide new insights on the neuropathophysiology of chronic tinnitus; therapies capable of reversing these aberrant patterns may reduce tinnitus distress.

Resting-State Brain Abnormalities in Chronic Subjective Tinnitus: A Meta-Analysis

“…Rauschecker et al (2010) developed a model to demonstrate structural and functional differences in ventromedial prefrontal cortex that were associated with tinnitus subjective loudness, indicating that frontal cortex may contribute to certain perceptual features of tinnitus. Resting-state fMRI studies have pointed out that the abnormalities of the frontal cortex could act as a direct mechanism of tinnitus chronification (Burton et al, 2012; Schmidt et al, 2013; Chen et al, 2014, 2015c,d, 2016), which are confirmed by the current meta-analysis. Based on the previous fMRI studies, the SFG has been regarded as a major integrative hub of the tinnitus network architecture (Chen et al, 2016), which can receive and integrate all kinds of information from different parts of the brain from inside and outside the body.…”

Increased Neural Activity in Mesostriatal Regions after Prefrontal Transcranial Direct Current Stimulation and l-DOPA Administration

“…fALFF has been applied as a proxy measure of spontaneous neural activity strength and has been used increasingly as a biomarker of neuropsychiatric diseases, including Alzheimer's disease (Zhou et al, 2015), schizophrenia (Xu et al, 2015), and depression (Liu et al, 2016). Several studies reported significant correlations of fALFF values and symptom severity in patients (Chen et al, 2015;Fryer et al, 2015) as well as behavioral performance in healthy humans (van Dam et al, 2015), suggesting a close association between resting-state fALFFs and specific behavioral parameters.…”

Alterations in Regional Homogeneity in Patients With Unilateral Chronic Tinnitus

“…Various functional magnetic resonance imaging (fMRI), electroencephalography, and magnetoencephalography (MEG) studies focusing on cerebral restingstate activity in targeted networks have shown alterations in functional connectivity or activity in different brain regions, including the auditory cortex (Burton et al, 2012;Kim et al, 2012;Maudoux et al, 2012a;Zhang et al, 2015), the prefrontal cortex (Kim et al, 2012, Maudoux et al, 2012a, 2012b, and the insula (Burton et al, 2012;Chen et al, 2015a;Vanneste, van de Heyning, & De Ridder, 2011) in tinnitus patients. Schmidt, Akrofi, Carpenter-Thompson, and Husain (2013) and Schmidt, Carpenter-Thompson, and Husain (2017) also observed a decreased functional connectivity in certain parts of the default mode network, particularly the prefrontal cortex and the cingulate posterior cortex with the precuneus.…”

“…In contrast, decreased ReHo values have been reported in the cuneus (Chen et al, 2015b) and the anterior lobe of the cerebellum (Yang et al, 2014) in subjects with tinnitus. This has led to the conclusion that chronic tinnitus induces changes in many cerebral networks, including the attention network (Chen et al, 2015b), the default mode network (Chen et al, 2015a), and the basal ganglia and the auditory cortex (Yang et al, 2014).…”