Abstract
Tinnitus is conscious auditory perception without corresponding external stimuli resulting from neuronal activity along auditory pathway either in peripheral or central auditory system. The exact origin, pathophysiologic pathway and its treatment is still under exploration. The main risk factor is hearing loss, but can occur in patients with normal hearing. Auditory brainstem response test helps to objectify this subjective complaint and aid in locating its origin. P300 is late latency auditory evoked potential, objective marker of cognitive potential. The purpose of our study was to ascertain any significant difference in P300 latency and amplitude values in cases of sensorineural hearing loss with tinnitus when compared to controls (normal hearing subjects) and also to find any correlation between severity of tinnitus and cognition. This was a case control study conducted at the department of ENT at Safdarjung Hospital, New Delhi between September 2016 to March 2018. The study comprised of one hundred and six patients, out of which fifty five patients were having sensorineural hearing loss with tinnitus and fifty one patients were normal hearing subjects. General medical and audiological history and examination was done. Significant increase in P300 latency and decrease in P300 amplitude was found in sensorineural hearing loss with tinnitus cases on comparing with controls. The similar pattern of P300 values was observed on increasing severity of tinnitus and degree of hearing loss. Hence, results revealed the role of cognition and involvement of central auditory pathway in tinnitus generation.
Keywords: Tinnitus, Cognition, P300 latency, P300 amplitude, Sensorineural hearing loss
Introduction
Tinnitus is derived from latin word ‘tinnire’ which describes conscious perception of auditory sensation in absence of corresponding external stimuli [1]. In India, approximately, 15–20% of the population suffer from tinnitus which affects their daily activities, but quality of life is severely affected in 1–3% of the population [2].Various peripheral and central models have been proposed in past, but still, its origin and exact pathophysiologic mechanisms is unknown. The main risk factor is hearing loss [3], but can occur in patients with normal hearing. Auditory brainstem response test helps to objectify this subjective complaint and aid in locating its origin. P300 is late latency auditory evoked potential, objective marker of cognitive potential. P300 is obtained by oddball paradigm and is neuronal co relation for attention, auditory differentiation capacity, short term memory and decision making abilities. However, how tinnitus exactly affects cognition is still under debate. Also, reciprocal link has been found to exist between tinnitus and cognition.
Materials and Methods
In this case control study conducted in Department of Otorhinolaryngology between September 2016 to March 2018 in a tertiary care hospital, 55 patients of sensorineural hearing loss with tinnitus and 51 subjects with normal hearing, were enrolled. The present study has been approved by the Ethical Committee of Safdarjung Hospital, New Delhi. The primary aim of the study was to find any significant difference in P300 values in cases of sensorineural hearing loss with tinnitus when compared to controls (normal hearing subjects). Secondary aim was to find any co relation between severity of tinnitus with cognition.
Patients with sensorineural hearing loss with subjective tinnitus (age > 18 years or any sex) not under any related treatment (like hearing aids) were included in the study. However, patients with objective tinnitus, definite middle ear pathology and co morbidities like diabetes mellitus, cardiovascular, neurological, psychiatric, behavorial dysfunctions were excluded from the study. The normal hearing patients (controls) were the attendants of the patients or patients coming to OPD for problems other than otological complaints. The age group, sex and socio demographic characteristics of the control was matched according to the cases. A well informed written consent was taken from all the participants. All patients were subjected to a careful assessment of general medical history to identify tinnitus-related pathologies and other health diseases. This was followed by an audiological history. The cases were asked in detail about characteristics of sound, its severity, any aggravating and relieving factors. Cases themselves graded their severity of tinnitus according to subjective scale called as visual analogue scale, wherein, score 1–3 = mild = 1, 4–6 = moderate = 2, 7–9 = severe = 3, 10 = incapacitating = 4. After completing the history, patients were subjected to the otoscopic and audiological (pure tone audiometry and auditory brainstem response test) examination. Sensorineural hearing loss was classified into mild = 26–40 dB, moderate = 41–60 dB, severe > 61 dB hearing loss(according to WHO criteria). Further, amplitude peak and latency of P300 was studied using NEURO AUDIO 2013.
Statistical Analysis
Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean ± SD and median. Normality of data was tested by Kolmogorov–Smirnov test. If the normality was rejected then non parametric test was used.
Statistical tests were applied as follows:
Quantitative variables were compared using Independent T test/Mann–Whitney Test (when the data sets were not normally distributed) between the two groups.
Qualitative variables were correlated using Chi Square test/Fisher exact test.
Spearman rank correlation coefficient was used to assess the association of various parameters with each other.
A p value of < 0.05 was considered statistically significant. The data was entered in MS EXCEL spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0.
Results
In our study, 55 patients of tinnitus with sensorineural hearing loss (30 males and 25 females) with and 51 normal hearing subjects (28 males and 23 females) were included in the study. The mean age of cases was 42.91 years and of controls was 41.63 years. There was no significant difference between the age, gender and education level of the groups. Results revealed significant increase in P300 latency (P < 0.0001) and decrease in P 300 amplitude (P < 0.0001) in patients with tinnitus and sensorineural hearing loss as compared to control group suggesting role of cognition in the former group.(as elucidated in Table 1). On increasing the degree of hearing loss, significant increase in P300 latency and decrease in P300 amplitude was observed in tinnitus with sensorineural hearing loss group (as shown in Figs. 1, 2) suggesting strong association between hearing loss (in tinnitus with hearing loss group) and cognition. Cognitive deficits in tinnitus with sensorineural hearing loss patients were further analysed by measuring P300 latency and amplitude in subgroups created by VAS score. The results revealed that with increasing severity of tinnitus, significant increase in P300 latency and decrease in P300 amplitude was observed. (as shown in Figs. 3, 4). This suggests relationship between severity of tinnitus and its affect on cognitive abilities.
Table 1.
There is significant increase in P300 latency and decrease in P300 amplitude on comparing Sensorineural hearing loss (SNHL) + tinnitus group with normal hearing subjects
| Parameter | Control group | Subgroup ‘SNHL + TINNITUS’ |
P value (Control and ‘SNHL + TINNITUS’) |
|---|---|---|---|
| P300 Latency | 318.32 ± 4.67 | 360.61 ± 21.01 | < .0001 |
| P 300 Amplitude | 10.16 ± 0.22 | 6.95 ± 1.83 | < .0001 |
Fig. 1.
The graph shows significant increase in P300 latency with increasing degree of sensorineural hearing loss (SNHL) in patients of sensorineural hearing loss with tinnitus (P < 0.0001), wherein, mild = 26–40 dB, moderate = 41–60 dB, severe > 61 dB hearing loss
Fig. 2.
The graph shows significant decrease in P300 amplitude with increasing degree of sensorineural hearing loss in patients of sensorineural hearing loss (SNHL) with tinnitus (P = 0.0001), wherein, mild = 26–40 dB, moderate = 41–60 dB, severe > 61 dB hearing loss
Fig. 3.
The graph shows significant increase in P300 latency with increasing severity of tinnitus in tinnitus with sensorineural hearing loss group (P = 0.009), wherein, 1–3 = mild = 1, 4–6 = moderate = 2, 7–9 = severe = 3, 10 = incapacitating = 4 (according to Visual Analogue Scale)
Fig. 4.
The graph shows significant decrease in P300 amplitude with increasing severity of tinnitus in tinnitus with sensorineural hearing loss group (P = 0.01), wherein, 1–3 = mild = 1, 4–6 = moderate = 2, 7–9 = severe = 3, 10 = incapacitating = 4 (according to Visual Analogue Scale)
Discussion
Cognitive impairment is an inclusive term used to describe any characteristic that acts as a barrier to the cognitive process [4]. Defect in cognitive abilities (like auditory selective attention and working memory) may have a close relationship with tinnitus, but this link is proposed to be reciprocal [5]. Tinnitus, apart from being associated with aberrant auditory perception, it is also related to non auditory symptoms like frustration, irritation and inadequate concentration. Hence, the role of cognitive impairment in tinnitus needs to be explored as it is still unclear due to limited data.
Tinnitus persistence is due to failure in the process of habituation. Henceforth, failure to switch attention resulting from defective cognitive abilities may lead to ongoing aberrant perception of sound. As tinnitus can disrupt attention and memory functions, alterations in cognitive functions would in turn play an important role in tinnitus generation and persistence [5]. In a study conducted by Trevis et al. [6] revealed role of altered interactions between non auditory neuro cognitive networks, apart from auditory dysfunction in maintaining chronic tinnitus awareness. By functional magnetic resonance imaging, they identified attenuated activation of core node of cognitive control network (the right middle frontal gyrus), and altered baseline connectivity between this node and nodes of salience and autobiographical memory networks. Studies have emphasized the role of cognitive deficit in chronic tinnitus, independent of any emotional effects. Heeren et al. [7] investigated the cognitive functioning of people with and without tinnitus in groups matched for emotional well-being (anxiety and depressive symptoms) showed impaired performance of the tinnitus group on tasks relying on cognitive control processes. In contrast, study conducted by Waechter and Brannstrom [8] concluded that tinnitus patients did not exhibit any obvious cognitive impairment. The inconsistency in findings may be due to differences in approaches applied in the studies or due to differential manifestation of cognition according to the severity of tinnitus. Studies conducted by Bankstahl and Gortelmeyer [9]; Das et al. [10] documented cognitive impairment in tinnitus correlating with the severity of tinnitus. Most of the studies include symptomatic profile of cognitive deficits leading to subjective biased variations. To objectify this subjective complaint and avoid confounding variables used in neurophysiological test, we have used the late latency auditory evoked potential, P300. It is obtained by discriminating two different random stimuli with differently occurring frequency called as the oddball paradigm. Stimulus discrimination is believed to be reflected electrophysiologically as a positive deflection in voltage with a latency of roughly 250–500 ms [11]. This paradigm belongs to important tools in electrophysiology which are used as measures of “working memory” [12]. It is objective, easy to perform, hence, we chose P300 for evaluating cognition. In a study conducted by Wang et al. [13], there was a significant difference P300 latencies between the two tinnitus subgroups (mild and severe according to cognitive ability screening instrument), further illustrating that cognitive deficits might be characteristic of tinnitus. There was no significant difference in the P300 amplitudes detected between the two patient subgroups. The study revealed that tinnitus patients on the severe end of the spectrum may be at risk for serious cognitive deficits, which may not be a secondary response to disease manifestations but a primary feature of the underlying disease. However, we found significant increase in P 300 latency and decrease in P300 amplitude in patients of tinnitus with sensorineural hearing loss when compared with healthy controls. Filha et al. [14], also found increase in P300 latency, reported decrease in P300 amplitude as in accordance with our study. They suggested that decrease in number of working neurons, decrease in neural activities and/or mismatch of firing of neurons could be possible factors associated with changes in long latency auditory evoke potential. Using Visual Analogue Scale, we classified tinnitus into four types: mild, moderate, severe and incapacitating. Our results showed significant increase in latency and decrease in P300 amplitude on increasing severity of tinnitus. So, a positive correlation was suggested between severity of tinnitus and cognitive impairment. Explanation as to why these cognitive deficits appear so severely in tinnitus patients, especially in severe tinnitus patients have been found by some. Leaver et al. [15] concluded that people with chronic tinnitus exhibit reduced grey matter in the ventromedial prefrontal cortex (vmPFC) compared to controls matched for age and hearing loss. Lee et al. [16] demonstrated deterioration of white fibres in the cortex of tinnitus patients. Vanneste et al. [17] demonstrated that cognitive changes in tinnitus patients are associated with changes in hippocampal activity as well as alteration in the anterior cingulate and insula [18]. The role of acoustic therapy in treating chronic and refractory tinnitus has been demonstrated. So, structural abnormalities in various parts of brain and cortical inter connectivity, better studied by functional magnetic resonance imaging explain the cognitive deficits. Also, effect of cognition in tinnitus opens area for clinicians to explore and cater to cognitive based therapies.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval
All procedures involving human participants were in accordance with the ethical standards of the institution.
Informed Consent
Informed consent was obtained from all individuals participants included in this study.
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