Masterthesis
Hypersensitivity Towards Human Sounds: an ERP Study in Misophonia Nigel A. Janssens
10306870 05-08-2017
Abstract
Misophonia is a psychiatric condition wherein individuals are typically hypersensitive to generic human sounds, such as eating or breathing, that ultimately cause intense feelings of distress or anger. It is often regarded as a disorder related to obsessive-compulsive disorder (OCD), through over-obsession of these highly specific trigger sounds.The current study evaluated the functionality of the brain its early auditory processing system and the excitatory/inhibitory balance to account for the hypersensitivity by comparing misophonia to OCD patients. A total of 67 patients diagnosed with misophonia and 42 OCD patients were examined during resting state and an oddball task. The event-related potentials corresponding to the presented tones were examined during the oddball task, whereas neural oscillatory activity was assessed during both eyes closed resting state and an auditory oddball task. The N1, mismatch negativity (MMN), P3, alpha and gamma activity were primarily examined in this respect. The results revealed that N1, MMN and P3 mean peak amplitudes were greater for misophonics than OCD patients. Both alpha and gamma activity were revealed to be greater in misophonia than OCD, suggesting that misophonics have a common, or perhaps a higher baseline of alpha activity and a natural E/I balance. Additional neural oscillatory effects have been exposed, namely an increase in beta and theta activity for misophonia patients during eyes closed resting state. The increased ERP and oscillatory responses might reflect a contributing factor of the hypersensitivity towards otherwise generic sounds through an altered early sound processing.
Hypersensitivity towards human sounds: an ERP study in misophonia
The recently identified mental disorder misophonia is typically characterised by a
hypersensitivity to generic human sounds (e.g. breathing or eating) or inanimate sounds (e.g. foot or pen-tapping) (Duddy & Oeding, 2014; Edelstein et al., 2013; Ferreira et al., 2013; Hadjupavlou et al., 2008; Jastreboff & Jastreboff, 2001; Kumar et al., 2017; Kumar et al., 2014; Schröder et al., 2013; Schröder et al., 2014). Misophonia is not officially classified, as both the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V; American Psychiatric Association, 2013) and the
International Statistical Classification of Diseases and Related Health Problems (ICD-10; World Health Organization, 1992) do not acknowledge misophonia yet. Before classifying misophonia as a new mental disorder, several issues need to be resolved, i.e. the symptomatological boundaries and the extent to which misophonia might be part of a broader disorder (Taylor, 2017). To initially explore misophonia, the first steps would be the identification, categorization and raising awareness - while exploration of possible malfunctioning processes in the neurobiological system should be next. One could distinguish three different stages in misophonia: 1) the fixation on specific human sounds, 2) the tendency to impulsively become furious over these sounds or express distress, and 3) the avoidance of specific settings that trigger symptomatic behaviour. Misophonics’ primary reaction to trigger sounds seems to avoid upsetting situations, however patients are also reported to overreact and enrage over trigger sounds (Edelstein et al., 2013; Schröder et al., 2013).
Nevertheless, the origin and the underlying neurobiological mechanisms of misophonia remain unknown and the disorder should be further examined to discover what exact neural
mechanisms cause the patients to be hypersensitive towards specific sounds. A clearer insight on the underlying neurobiological mechanisms of misophonia could grant misophonics an understanding of their disorder and might lead to more awareness and provide additional information. This allows for expert consensus to decide whether misophonia can be classified as a stand-alone disorder, or that
misophonia is rather a collection of symptoms of broader disorders. Moreover, the development of suitable treatment targets might develop alongside an understanding of the underlying neural mechanisms.
To date, misophonia is often regarded as a disorder related to obsessive-compulsive disorder (OCD), and is therefore hypothesised as an obsessive-compulsive spectrum disorder (OCSD). However, the cluster of symptoms for misophonics does not entirely fit the criteria for OCD, as misophonia patients express intense distress or anger towards, and in anticipation of, triggers sounds (Schröder et al., 2013). The overlapping symptomatology with OCD might reveal several distinctive malfunctioning neurological processes of misophonia. Misophonics are speculated to be
over-obsessed with either animate or inanimate trigger sounds, which may lead to an increased arousal to auditory stimuli due to endless repeating of the triggering actions in one’s mind. These sounds might thus lead to intense feelings of distress and anger (Bruxner, 2015). Interestingly, the disorder also shows symptomatological overlap with sensory over-responsiveness (SOR). SOR reflects extreme agitation to particular sensory cues, including auditory stimuli, which could infer a potential
influence of SOR on the symptomatology of misophonia, as misophonics are likewise over-sensitive to specific trigger sounds. Remarkably, SOR is often found in comorbidity with OCD, which raised the suggestion that misophonia might be a combination of symptoms found in both disorders (Taylor, 2017). This reinstates the amount of overlap between multiple disorders hence the suggestion is raised by Taylor (2017) whether misophonia could be labelled as a stand-alone disorder.
An alternative psychological explanation for the hypersensitivity experienced in misophonia might involve a negative conditioning of trigger sounds to a negative event the patient has
experienced. Trigger of misophonic symptoms may lead to a negative emotional reaction (anger, anxiety or distress), which may be negatively reinforced by their response (Cavanna & Seri, 2015; Webber & Storch, 2015). Though misophonics usually have sufficient self-reflection and coping
skills to soothe their overreaction towards trigger sounds (Schröder et al., 2013), to avoid situations that are likely to trigger their symptoms, misophonics might decide to rather withhold of attending social events that involve eating or close interaction with other individuals. Misophonia may therefore be a traumatic response that is evoked by negative experiences instead of, or in combination with, hypersensitivity towards trigger sounds. The negative conditioning of trigger sounds to negative emotions appears to generate feelings of distress or anger during misophonics’ symptomatic behaviour. This rationale was reinforced by a study by Rouw and Erfanian (2017), whom found that the intensity of comorbid posttraumatic stress disorder (PTSD) was correlated to symptom dimensions of misophonia; misophonics suffering from severe PTSD experienced more intense symptomatic behaviour.
An alternative basis of the disorder might depict an overlap with symptoms of obsessive-compulsive personality disorder (OCPD). OCPD is characterized by cognitive inflexibility and moralism; these characteristics might also play a role in misophonia. The literature shows that roughly half of misophonia patients indeed seem to suffer from comorbid OCPD. Patients with misophonia might be particularly sensitive for people who violate the societal norms by eating, chewing or breathing loudly (Schröder et al., 2013). OCPD symptoms mainly consist of a high level of cognitive inflexibility and moralism, which may prompt the patient to mercilessly criticize one’s behaviour if they fail to meet the misophonics’ expectations regarding societal norms (American Psychiatric Association, 2013). Misophonics express an overlap with these symptoms regarding their state of anger when they perceive specific human sounds, as they have a general conception of how one should behave in society.
While current models for misophonia are yet in their infancy, possible abnormalities in functional connectivity may expose sources for the hypersensitivity towards specific sounds. One plausible underlying neural construct might be an altered interoception of trigger sounds. Kumar et al. (2017) used functional magnetic resonance imaging to identify key brain structures that are
activated during exposure to trigger sounds. Trigger sounds (e.g. breathing or eating), but not
unpleasant sounds (e.g. babies crying), cause a hyperactivity of the anterior insular cortex (AIC) and this area is linked to an irregular functional connectivity to several brain areas, including temporal, medial frontal and medial parietal regions. The authors conclude that the hypersensitivity present in misophonia may be caused by wrongful processing of otherwise harmless trigger sounds, i.e. stimuli are attributed atypical salience values, which are then coupled to an abnormal perception of internal body states that ultimately lead to the hypersensitivity towards the trigger sounds.
The hypersensitivity may be further elucidated by cortical responses during exposure to aural stimuli. Specifically, the sensory sensitivity present in misophonia may be reflected by specific patterns of brain activity, which might reveal the underlying mechanisms of the disorder and clarify the overlap with OCD. Several components of an event-related potential (ERP) have been linked to a variety of early perception mechanisms. The sensory components that reflect early attention and modality processing include the N1 and mismatch negativity (MMN; Näätänen, 1992; Rinne et al., 2006). These components reflect the detection of acoustic changes when a sudden change of sounds or intensity occurs. Both N1 and MMN are often examined using an (auditory) oddball paradigm, where participants are presented repetitive sounds (standard) and deviant sounds (oddballs) are presented randomly (Näätänen & Picton, 1987). Patients suffering from misophonia seem to express a reduced N1, which may reflect the presence of atypical auditory processing (Schröder et al., 2014). Diminished N1 responses, however, have also been found in various other mental disorders, such as major depressive disorder (Burkhart & Thomas, 1993) and schizophrenia (Salisbury et al. 2010). More interestingly, an attenuated N1 showed connections with an increase in impulsivity in patients suffering from an antisocial personality disorder (APD; Lijffijt et al., 2012). This finding might imply a role for the impulsive enragement of misophonics during symptomatic behaviour as
misophonics present a comparable impulsivity when they get aroused. In contrast, OCD patients tend to have a longer latency on N1 (Morault et al., 1997; Di Russo et al., 2000). The MMN reflected by
OCD patients showed no clear distinctions when compared to healthy individuals (Yamamuro et al,, 2016). There is currently no data on the MMN in misophonia yet.
Lastly, the P300 component occurs typically around 300 ms following stimulus onset and is considered to reflect the processing of information, e.g. generating appropriate responses to certain situations (Linden, 2005) and consciousness (Picton, 1992). The P300 in OCD patients was found to be attenuated (Yamamuro et al., 2016), whereas research on the P300 in misophonia is deficient and needs further examination. Despite the resemblance between misophonia and OCD patients on the basis of symptomatology, differences in N1, MMN and P3 could potentially define one of several distinctive neurocognitive markers.
Patterns of neural oscillations might also elucidate a cause for the hypersensitivity as a consequence of atypical sensory processing. Neuronal events are often portrayed by excitatory and inhibitory synaptic input, which leads to the generation of appropriate responses to perceived sensory cues. When the excitatory and inhibitory input, or excitatory/inhibitory balance (E/I) becomes
impaired, the brain might malfunction as typically seen in epilepsy (Kaplan, 2010). Brain activity appears to be impaired in OCD patients as they exhibit a disturbed excitatory/inhibitory balance, which is especially observable during resting state (Leyfer et al., 2006; Richter et al., 2012). The E/I balance is not, however, solely impaired in OCD, but in multiple mental disorders, such as autism and ADHD (Pizzarelli & Cherubini, 2011). The hypothesized E/I imbalance in these disorders is known to affect N1 and MMN components of the ERP (Billingslea et al., 2014; Cooray et al., 2014; Gandal et al., 2012), but also oscillatory responses such as gamma frequency (Gandal et al., 2012; Yizhar et al., 2014).
According to the extant neurophysiological data, several potential targets for the clarification of misophonia have recently been identified. Misophonics, for example, might experience atypical early sound processing, as they seem to express diminished N1 during an oddball task in comparison to healthy individuals. The MMN may reflect an altered attention allocation to auditory stimuli. The
P300 could potentially assess the ability to generate appropriate responses to specific scenarios and to become conscious of sensory cues.
Furthermore, it may be likely that misophonics express a dysfunction in neural oscillations, such as an E/I imbalance in the cortex. The suppression of auditory signals in the auditory cortex might be impaired due to a defective E/I balance, and as a consequence renders misophonics more susceptible to human sounds healthy individuals would otherwise not consider harmful. Note, however, that changes on the neurophysiological level in misophonia patients are likely to develop concurrently and not separately. As mentioned before, the E/I balance is known to influence the ERP and oscillatory responses. The diversity of misophonia is reinstated by the fact that misophonics may also be aroused by inanimate sounds, rendering it unlikely that the symptomatology can be solely explained by brain activity. Instead, altered brain activity should be considered a contributing factor that, in combination with psychological factors, may shape the disorder.
The current study aims to investigate whether attention-based components of brain activity are impaired for patients suffering misophonia. The results could provide evidence for a distinct characterization of patterns of brain activity and could be used as a neurocognitive marker for
misophonia. The National Institute of Mental Health (NIMH) recently posed research domain criteria (RDoC) for novel methods of studying mental disorders (Insel, 2014). A variety of information, ranging from genomics to self-report, is integrated to comprehend the basic dimensions of human functioning for clinical as well as sub-clinical dimensions. Precisely this is what the current study aims to accomplish by investigating neurocognitive markers of misophonia. Discovering the neural mechanisms that cause misophonia is essential, as they currently remain unknown.
Due to the degree of overlapping symptomatology of misophonia with OCD, the primary goal of the study is to investigate the ERP response of both misohponia and OCD patients. The secondary objective is to investigate the degree of oscillatory activity in misophonia patients during resting state and an oddball task, again in comparison to OCD patients. The tertiary objective is to
examine the relationship between symptom dimensions and ERP and oscillatory responses. Prior research has well documented effects on N1, MMN and P3, thus to examine the first objective, misophonia patients are hypothesised to elicit a more diminished N1 and a greater MMN and P3 than OCD patients. Misophonia patients are also hypothesised to express an E/I imbalance similar to OCD patients, which may infer atypical processing of excitatory and inhibitory synaptic input. Furthermore, a decrease in alpha power in the auditory cortex during resting state and oddball task is hypothesised to be observed in misophonia patients when compared to OCD patients. This decrease could be the cause for an inhibited suppression of acoustic sounds and might be the factor
responsible for the hypersensitivity. The extent to which symptom severity in misophonia affects ERP and oscillatory responses is hypothesised to reveal a more attenuated N1 and a stronger MMN and P3 in relation to increasing severity of the misophonia symptoms. Patients who score high on the Amsterdam Misophonia Scale (A-Miso-S, Schröder et al., 2013) are predicted to express a more diminished N1 and a greater MMN and P3 than patients who score low on the questionnaire.
Likewise, symptom dimension are hypothesised to affect oscillatory responses as symptoms become increasingly intense, resulting in an attenuated activity of the neural oscillations.
Method Participants
A total of 67 patients with misophonia (females = 51) aged 15-68 years (M = 36.0, SD = 15.3 years) and 42 patients with OCD (females = 25) aged between 21 and 74 years (M = 43.3, SD = 13.1 years) participated in this study. Both the misophonia and the OCD group were selected to be devoid of any psychiatric comorbidity. Severity of misophonia symptoms was assessed by the A-Miso-S questionnaire (Schröder et al., 2013). Patients with mild symptoms (n = 18) scored an average of 27.6, SD = 3.1 on the A-Miso-S questionnaire, whereas patients with severe symptoms (n = 11) scored an average of 34.4, SD = 4.7. Mental condition was evaluated by the Hamilton Anxiety Rating Scale (HAM-A; Hamilton, 1959), Impact of Event Scale –Revised (IES-R, Weiss & Marmar,
1979) and Social Interaction Anxiety Scale (SIAS, Mattick & Clarke, 1998). All patients were clinically stable and provided written consent prior to participating. The local medical ethics committee of the Academic Medical Centre of Amsterdam approved the studies.
Procedure
Prior to the intake at the Department of Psychiatry, patients were requested to fill in the A-MISO-S questionnaire regarding symptoms dimensions of misophonia. Each participant was assessed for possible psychiatric comorbidity by means of a Structured Clinical Interview for DSM-IV Axis II (SCID-II, First et al., 1997). Following this initial screening, the patients were admitted to the study. EEG was registered in all patients and resting state activity was measured for a total of ten minutes; five minutes eyes open, followed by five minutes with their eyes closed. Participants were subsequently presented aural stimuli for a total duration of twelve minutes and were instructed to watch a silent, neutral movie (BBC’s TV Serie Life) during the mismatch negativity task. All experiments were conducted at the AMC’s research facilities.
EEG Acquisition and Analysis
Participants were presented a pseudorandomized sequence consisting of 1500 auditory stimuli in a classic oddball task (Presentation 11.3, Neurobehavioral Systems Inc., Albany, CA, USA). The standard tones were emitted in 90% of the stimuli and had a frequency of 1000 Hz, whereas the deviant tone ranged higher than the standard tone (4000 Hz). The deviant tone was never presented successively and was presented in 10% of the stimuli. The participants were instructed to press a button as soon as the deviant tone was perceived. During the task, participants watched a neutral episode of BBC’s Life on either insects or birds. The volume of the series was however turned completely down, thus the stimulus sounds were well detectable during emission.
Patients’ EEG data were obtained using a WaveGuard 10-5 cap system designed by ANT. The cap contained a total of 64-Ag/AgCl electrodes, and covered all cortical regions, ranging from frontal to parietal areas. The EEG sampling rate was set to 512 Hz.
EEG data were cleaned for analysis using MatLab. Firstly, flatline and excessive noise were cut out by discarding bad channels, followed by re-referencing of the channels to the mastoid. Data were thereafter two-pass filtered at 1-45 Hz using a zero-phase FIR filter. Manual visual review and independent component analysis (Jung et al., 2001) were applied to extract possible bad channels, bad signal episodes, and muscle or blink artefact components.
Epoch limits were set to -200 to 600 milliseconds. Average amplitudes for all ERP
components, i.e. N1, MMN and P3, were computed for each selected channel. Based on the average ERP response, specific time intervals were selected to evaluate mean peak amplitudes per channel and per group. Misophonia had selected time intervals of 120 to 240 milliseconds for N1 to calculate the most negative amplitude, an interval spanning from 140 to 290 milliseconds to determine the deflection of MMN, and lastly a time window of 290 to 440 milliseconds to evaluate the most positive amplitude to assess the P3. A time interval of 120 to 220 milliseconds was selected to evaluate the most negative deflection of N1 for OCD patients. The MMN time interval was, again, set at 140 to 290 milliseconds and the window to examine the most positive deflection of P3 was fixed at 320 to 420 milliseconds (see figure 2d and 2e). Since standard tones presented immediately after a deviant may also be considered deviant from the previous stimulus, standard ERPs were calculated from epochs directly before deviant trials only.
Subsequently, specific channels were selected to analyse the average ERP response (see figure 1). Figures 2a, 2b and 2c show distinctions in activity topography per component, allowing for the selection of channels with the highest grand-average ERP response per component. The effect of N1 and P3 was strongest for channel FCz, irrespective of group, while the MMN was strongest for channel CPz (see figure 2a, 2b and 2c).
To analyse theta, beta and gamma power, a selection in channels was outlined, namely FC1, FC2 and FCz in the frontal-central regions, CP1 and CP2 in the central-parietal areas and PO3 and PO4 in the occipital-parietal field (see figure 1). In contrast, an alternative selection of channels was utilized to assess the degree of alpha power in areas of interest more accurately. The selected
channels were F3, F4 and FCz to assess alpha power in the frontal areas of the cortex, C5 and C6 for closely measuring alpha power emitted in the auditory cortex, and PO3 and PO4 for the visual cortex (see figure 1).
Figure 1. Selection of channels to assess ERP and oscillatory response. Highlighted in blue is CPz to assess MMN. Highlighted in yellow are the channels used to measure ERP and oscillatory responses, i.e. N1, P3 and all four oscillatory frequencies. Highlighted in green are the channels used to evaluate alpha power.
Figure 2a-e. Grand-average topographies of ERP response (n = 98) and average group ERP response. Figure 1a, the top left headplot, depicts a grand-average topography of N1 expressed during both pre-deviant standard and deviant tones. Figure 1b, the middle left headplot, displays the grand-average MMN elicited during the presentation of deviant tones. Figure 1c, the bottom left headplot, displays the grand-average P3 evoked during the presentation of deviant tones. Figure 1d, located on the top right, demonstrates misophonia’s ERP response (n = 61) during both pre-deviant standard and deviant tones. Figure 1e, located on bottom right, demonstrates OCD’s ERP response (n = 37) during both pre-deviant standard and deviant tones. Shaded areas indicate the time windows to assess N1, MMN and P3.
Statistical Analyses
Specific areas of interest were selected to properly analyse the ERP responses: FCz and CPz. ERP activity measured by these channels was compared by one-way ANOVAs, to assess plausible differences in N1, MMN and P3. Pearson’s Correlation Coefficient examined interaction effects between pre-deviant standard and deviant tones for N1. Moreover, paired samples t-tests compared the evoked N1 amplitude during pre-deviant standard and deviant tones. The extent of symptom dimensions was examined similarly by using one-way ANOVAs for ERP responses and Pearson’s Correlation Coefficient for interaction effects between both stimuli.
Neural oscillatory activity was explored for alpha, beta, theta and gamma power, on 7 distinct locations, between misophonia and OCD, but also for symptom dimensions, using one-way
ANOVAs. A false discovery rate was set at 10% to correct for multiple comparisons, due to the explorative nature of the analyses regarding oscillatory activity (Benjamini & Hochberg, 1995).
Lastly, HAM-A, IES-R, SIAS scores and medication usage were correlated to both ERP and neural oscillatory activity to control for potential confounding factors using Pearson’s Correlation Coefficient. These factors too have been corrected for multiple comparisons using a false discovery rate of 10% (Benjamini & Hochberg, 1995).
Results
N1
N1 was stronger for deviant tones (MDeviant = -3.02 µV, SD = 1.85), than in pre-deviant standard tones (MPre-deviant = -1.15 µV, SD = 1.42), irrespective of group; t(97) = 9.503, p < .05 (see figure 2d, 2e and 3). The exemplification of any significant group effect of N1 during pre-deviant standard tones remained absent, as elucidated by one-way ANOVA (MMisophonia = -.94 µV, SD = 1.38 vs. MOCD = -1.48 µV, SD = 1.44; F(1,96) = 3.423, p = .067). Symptom
dimensions likewise did not significantly affect N1 during pre-deviant standard stimuli (MMild = -.90 µV, SD = 1.34 vs. MSevere = -.89 µV, SD = 1.31; F(1,96) = 0.081, p = .778). In contrast, N1 group effect during deviant tones was significantly greater in the frontal-central region for misophonia (MMisophonia = -3.41 ± 1.75 µV vs. MOCD = -2.38 ± 1.86 µV; F(1,96) = 7.468, p = .007). There was, however, no distinction in N1 group effect during deviant tones between mild misophonia (MMild = -3.85 µV, SD = 1.86) and severe misophonia (MSevere = -2.85 µV, SD = 1.81; F(1,26) = 1.854, p = .185).
Furthermore, interaction effects were revealed between the pre-deviant standard tone and deviant tone (see figure 3). Mean N1 amplitudes evoked by the pre-deviant standard tone and deviant tone were slightly related in misophonia (r = .45, p < .05), but not in OCD (r = .28, p = .090). Interaction effects between the pre-deviant standard tone and deviant tone were not observed for symptom dimensions in either conditions, i.e. mild misophonia (r = .438, p = .063) and severe misophonia (r = .425, p = .220).
Altogether, the results entail a statistically significant distinction in N1 peak amplitude during the presentation of deviant tones between misophonia and OCD. Patients diagnosed with
misophonia revealed greater N1 peak amplitude than OCD patients. No statistically significant differences were observed for symptom dimensions. An interaction effect was discovered between pre-deviant standard and deviant tones in misophonia patients, suggesting that the significant distinctions between the groups may have been caused by generally elevated N1 values in misophonia patients. No statistically significant distinctions have been objectified for N1 peak amplitudes during both pre-deviant standard and deviant tone stimulation and symptom severity. The results indicate larger N1 amplitude in misophonia than in OCD, thus hinting at an altered early sound processing for misophonia.
Figure 3. Group effects of N1 during the presentation of standard and deviant tones. The group averages of N1 are depicted for misophonia and OCD during the presentation of pre-deviant standard and pre-deviant tones. The pre-deviant tone evoked a significantly greater N1 in both
groups. Mean N1 peak amplitude differed significantly for misophonia and OCD. Interaction effects were observed for stimuli type in misophonia, but not in OCD. * Indicates a significant difference between groups at a significance level of α = .05.
MMN
The mismatch negativity exposed clear distinctions between misophonia and OCD (see figure 2d, 2e and 4). Misophonia patients (MMisophonia = -2.13 µV, SD = 1.74) were observed to elicit a greater MMN than OCD patients (MOCD = -1.23 µV, SD = 1.71) in the central-parietal region, F(1,96) = 6.188, p = .015. However, no significant differences were found in MMN, between mild (MMild = -2.77 µV, SD = 1.59) and severe misophonia (MSevere = -2.29 µV, SD = 2.16; F(1,26) .098, p = .757). These results raise the suggestion that misophonics express a significantly greater MMN in comparison to OCD patients during an oddball task and may reflect an altered attention allocation to deviating sounds.
Figure 4. Group effects of MMN during the presentation of deviant tones. The group averages of MMN are depicted for misophonia and OCD during the presentation deviant tones.
The mismatch negativity was significantly greater in misophonia than in OCD at a significance level of α = .05.
P3
Statistically significant discrepancies in P3 amplitude were likewise observed in misophonia and OCD patients (see figure 2d, 2e and 5). The P3 elicited in the frontal-central region unveiled a significantly greater P3 in misophonia, as elucidated by one-way ANOVA (MMisophonia = 4.35 ± 3.02 µV vs. MOCD = 2.98 ± 2.46 µV; F(1,96) = 5.403, p = .022). The degree of symptom severity did not influence the P3, as significant differences between mild (MMild = 4.57 µV, SD = 2.87) and severe misophonia (MSevere = 4.54 µV, SD = 3.34) remained absent; F(1,26) = 0.009, p = .926. The results suggest that the P3-amplitude expressed during deviant tones is significantly greater in misophonia, in comparison to OCD, indicating a greater ability to generate appropriate responses in specific scenarios and to become conscious in misophonia.
Figure 5. Group effects of P3 during the presentation of deviant tones. The group averages of P3 are depicted for misophonia and OCD during the presentation deviant tones. The P3 was significantly greater in misophonia than in OCD at a significance level of α = .05.
Neural Oscillatory Power
Alpha Activity
Six out of seven selected channels measured a significantly different alpha power between misophonia and OCD during eyes closed resting state, each separate analysis was corrected for multiple comparisons by means of a false discovery rate set at 10 % (Benjamini & Hochberg, 1995). The channels F3, FCz, C5, C6, PO3 and PO4 each showed a significantly higher alpha activity during eyes closed in misophonia than in OCD, at a significance level of .10 (see figure 6a and 6b, table 1a). No significant differences in alpha power were observed
between mild and severe misophonia patients (see table 1b).
A single channel, i.e. PO3, measured a significantly distinct alpha power during the mismatch negativity task between misophonia and OCD (see figure 6c and 6d, table 1a). In contrast, mild misophonia patients expressed a significantly higher alpha activity than severe misophonia patients during the oddball task in the F3, F4, FCz and C5 regions, all corrected p-values < .10 (see table 1b).
The observed alpha power during eyes closed resting state was significantly higher in misophonia on six out of seven selected channels, suggesting that alpha power in general is higher for misophonics than for OCD patients. Merely a single channel yielded significant differences in alpha activity during the oddball task between groups, hence an increased alpha power for misophonia, either locally or globally, is unlikely to have occurred. Furthermore, the results suggest that the severity of misophonia symptoms negatively affects alpha power during an oddball task, wherein patients are presented a multitude of aural stimuli, while this effect was not observed during eyes closed resting state.
ALPHA OSCILLATORY POWER - GROUP AVERAGES AND P-VALUES
Misophonia OCD P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task F3 27.05 ± 4.43 22.43 ± 3.66 25.00 ± 4.80 21.71 ± 3.90 0.032* 0.364 F4 27.21 ± 4.38 22.70 ± 3.47 25.38 ± 4.70 21.97 ± 3.91 0.053 0.333 FCZ 28.25 ± 4.34 24.25 ± 3.14 25.95 ± 4.83 23.32 ± 3.39 0.016* 0.169 C5 25.96 ± 4.32 21.46 ± 3.97 23.35 ± 5.18 19.94 ± 4.29 0.008* 0.078 C6 25.86 ± 4.44 21.30 ± 4.32 23.23 ± 5.25 20.07 ± 4.38 0.009* 0.179 PO3 29.86 ± 4.85 24.12 ± 3.73 27.08 ± 6.30 22.24 ± 3.96 0.015* 0.020* PO4 29.77 ± 4.92 23.85 ± 3.91 27.12 ± 6.55 22.32 ± 4.13 0.024* 0.068
ALPHA OSCILLATORY POWER AND SYMPTOM DIMENSIONS – GROUP AVERAGES AND P-VALUES
Mild Misophonia Severe Misophonia P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task F3 26.64 ± 4.44 23.55 ± 2.89 27.27 ± 5.88 20.19 ± 3.66 0.744 0.013* F4 27.04 ± 4.40 24.20 ± 2.76 27.49 ± 5.85 20.78 ± 3.62 0.815 0.009* FCZ 28.02 ± 4.25 25.44 ± 2.46 28.35 ± 5.80 22.38 ± 3.57 0.858 0.013* C5 25.58 ± 4.39 22.60 ± 3.01 26.52 ± 5.70 19.33 ± 4.78 0.621 0.034* C6 25.46 ± 4.84 22.46 ± 3.43 26.18 ± 5.68 19.42 ± 4.75 0.720 0.061 PO3 30.51 ± 5.77 25.54 ± 3.32 30.97 ± 5.63 23.55 ± 4.77 0.834 0.206 PO4 29.81 ± 6.09 25.04 ± 3.47 30.65 ± 5.66 22.96 ± 5.12 0.714 0.211 Table 1a and 1b. Group effects and statistical values for one-way ANOVAs and t-tests on
alpha power during each task and symptom dimensions. Alpha power was examined during eyes closed and the oddball task. In table 1a the group effects and statistical values of the differences in alpha power between groups are depicted for each channel and task by one-way ANOVA. Table 1b presents the group effects and statistical values of the differences between mild and severe misophonia in alpha power for each channel and task by Student’s t-test. * Indicates a significant difference between groups at a false discovery rate of 10 %.
Figure 6a-d. Alpha power expressed during eyes closed (n= 65 vs. n = 36) and oddball task (n= 61 vs. n = 37) for misophonia and OCD. The top left headplot displays alpha power during eyes closed in misophonia (6a), the top right for OCD (6b). The bottom left illustrates alpha power during the oddball task in misophonia (6c), the bottom right for OCD (6d). Misophonics expressed a stronger alpha activity during eyes closed in the frontal-central, central and occipital-parietal regions. During the oddball task, alpha power transpired to a greater degree in the left occipital-parietal area for misophonics.
Beta Activity
Significant differences in beta activity manifested between both groups during eyes closed. Five out of seven selected channels indicated significantly stronger beta oscillations in misophonia: FC1, FCz, CP1, PO3 and PO4 at a false discovery rate of 10 % (see figure 7a and 7d, table 2a). Symptom dimensions did not affect beta power by any means, all corrected p-values > .10 (see table 2b).
Neither misophonia nor OCD patients showed a significantly stronger beta activity during the oddball task; all corrected p-values > .10 (see figure 7c and 7d, table 2a). In contrast, symptom severity negatively influenced beta power during the oddball task, as a total of five out of seven channels measured significantly greater beta activity in mild misophonics: the FC1, FC2, FCz, CP1 and CP2 (see table 2b).
Altogether, these results suggest an increase in the amount of beta oscillations in misophonia during eyes closed for nearly the entire selected regions of interest, whereas beta activity during the oddball task did not indicate such effects. Beta power is furthermore,
suggested to be significantly greater for misophonics with mild symptoms than misophonics with severe symptoms, in the frontal, frontal-central and central-parietal regions during an oddball task, but not eyes closed.
BETA OSCILLATORY POWER - GROUP AVERAGES AND P-VALUES
Misophonia OCD P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task FC1 19.68 ± 2.92 18.39 ± 2.72 18.18 ± 3.75 18.52 ± 2.86 0.028* 0.822 FC2 19.80 ± 2.85 18.51 ± 2.54 18.55 ± 3.54 18.69 ± 3.06 0.056 0.748 FCZ 20.07 ± 2.77 18.90 ± 2.55 18.54 ± 3.64 19.01 ± 2.74 0.019* 0.841 CP1 19.76 ± 2.91 18.33 ± 2.33 18.36 ± 3.39 18.12 ± 2.94 0.032* 0.699 CP2 19.67 ± 2.92 18.20 ± 2.46 18.39 ± 3.42 18.07 ± 2.97 0.050 0.809 PO3 19.72 ± 2.89 17.62 ± 2.35 18.01 ± 3.68 17.17 ± 2.85 0.012* 0.395 PO4 19.55 ± 3.03 17.35 ± 2.48 18.05 ± 3.78 17.17 ± 3.03 0.032* 0.740
BETA OSCILLATORY POWER AND SYMPTOM DIMENSIONS - GROUP AVERAGES AND P-VALUES
Mild Misophonia Severe Misophonia P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task FC1 19.64 ± 2.45 18.95 ± 1.66 18.94 ± 3.93 15.87 ± 3.01 0.555 0.002* FC2 19.80 ± 2.43 19.02 ± 1.80 19.11 ± 3.99 16.43 ± 2.78 0.566 0.006* FCZ 20.10 ± 2.35 19.50 ± 1.61 19.37 ± 3.71 16.79 ± 2.94 0.522 0.004* CP1 19.92 ± 2.39 18.92 ± 1.38 19.08 ± 4.00 16.60 ± 2.80 0.481 0.007* CP2 19.59 ± 2.76 18.75 ± 1.51 19.08 ± 3.85 16.50 ± 2.90 0.682 0.012* PO3 19.84 ± 3.15 17.84 ± 1.59 20.21 ± 2.97 16.72 ± 2.52 0.757 0.158 PO4 19.24 ± 3.49 17.64 ± 1.44 19.76 ± 3.65 16.08 ± 3.04 0.706 0.075 Table 2a and 2b. Group effects and statistical values for one-way ANOVAs and t-tests on
beta power during each task and symptom dimensions. Beta power was examined during eyes closed and the oddball task. In table 2a the group effects and statistical values of the differences in beta power between groups are depicted for each channel and task by one-way ANOVA. Table 2b presents the group effects and statistical values of the differences between mild and severe misophonia in beta power for each channel and task by Student’s t-test. * Indicates a significant difference between groups at a false discovery rate of 10 %.
Figure 7a-d. Beta power expressed during eyes closed (n= 65 vs. n = 36), eyes open (n= 18 vs. n = 4) and oddball task (n= 61 vs. n = 37) for misophonia and OCD. The top left headplot displays beta power during eyes closed in misophonia (7a), the top right for OCD (7b). The bottom left illustrates beta power during the oddball task in misophonia (7c), the bottom right for OCD (7d). Misophonics expressed a stronger beta activity during eyes closed in left occipital-parietal region. OCD patients exerted a higher amount of beta power in the frontal-central areas during eyes open resting state.
Gamma Activity
The degree of gamma oscillations was likewise found to be significantly greater in misophonia. Six of the seven selected regions of interest assessed a greater gamma activity at the 10 % level: FC1, FCz, CP1, CP2, PO3 and PO4 (see figure 8a and 8b, table 3a). Gamma
oscillatory activity during eyes closed was, however, unaffected by symptom dimensions; all corrected p-values > .10 (see table 3b).
Gamma frequency observed during the oddball task did not elucidate any significant differences in power between misophonia and OCD; all corrected p-values > .10 (see figure 8c and 8d, table 3a). Symptom dimensions affected the gamma activity on but a single channel: FC1, corrected p-value < .10 and > .10 for the non-significant channels (see table 3b). Conferring the presented results, gamma power is suggested to be increased in misophonia during eyes closed in nearly all regions of interest, but not during the oddball task. Likewise, symptom dimensions of misophonia are observed not to influence gamma power during eyes closed resting state and an oddball task.
GAMMA OSCILLATORY POWER - GROUP AVERAGES AND P-VALUES
Misophonia OCD P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task FC1 13.71 ± 2.94 13.57 ± 2.21 12.38 ± 2.49 13.76 ± 2.00 0.025* 0.678 FC2 13.81 ± 2.81 13.67 ± 2.00 12.76 ± 2.00 13.85 ± 2.22 0.051 0.666 FCZ 14.03 ± 2.70 13.96 ± 2.01 12.70 ± 2.21 14.14 ± 1.90 0.013* 0.659 CP1 13.55 ± 2.87 13.34 ± 1.88 12.27 ± 2.09 13.33 ± 2.07 0.020* 0.996 CP2 13.43 ± 2.89 13.19 ± 1.97 12.26 ± 1.94 13.27 ± 2.08 0.033* 0.851 PO3 13.88 ± 2.86 13.02 ± 2.30 12.08 ± 2.50 12.67 ± 2.20 0.002* 0.466 PO4 13.92 ± 3.01 12.83 ± 2.31 12.13 ± 2.37 12.72 ± 2.52 0.003* 0.819
GAMMA OSCILLATORY POWER AND SYMPTOM DIMENSIONS - GROUP AVERAGES AND P-VALUES
Mild Misophonia Severe Misophonia P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task FC1 13.71 ± 1.89 13.81 ± 1.22 13.12 ± 5.01 11.58 ± 3.26 0.659 0.015* FC2 14.01 ± 1.98 13.92 ± 1.24 13.26 ± 4.82 12.28 ± 2.97 0.560 0.049 FCZ 14.20 ± 1.71 14.27 ± 1.05 13.44 ± 4.71 12.51 ± 3.18 0.536 0.039 CP1 13.74 ± 1.86 13.60 ± 1.17 13.12 ± 4.91 12.06 ± 2.96 0.631 0.058 CP2 13.43 ± 2.15 13.46 ± 1.11 13.07 ± 4.97 11.97 ± 3.25 0.790 0.086 PO3 14.11 ± 3.00 13.11 ± 1.70 14.49 ± 3.84 12.05 ± 2.80 0.770 0.222 PO4 13.87 ± 3.22 13.21 ± 1.50 14.33 ± 4.53 11.72 ± 3.27 0.752 0.109 Table 3a and 3b. Group effects and statistical values for one-way ANOVAs and t-tests on
gamma power during each task and symptom dimensions. Gamma power was examined during eyes closed and the oddball task. In table 3a the group effects and statistical values of the differences in gamma power between groups are depicted for each channel and task by one-way ANOVA. Table 3b presents the group effects and statistical values of the differences between mild and severe misophonia in gamma power for each channel and task by Student’s t-test. * Indicates a significant difference between groups at a false discovery rate of 10 %.
Figure 8a-d. Gamma power expressed during eyes closed (n= 65 vs. n = 36), eyes open (n= 18 vs. n = 4) and oddball task (n= 61 vs. n = 37) for misophonia and OCD. The top left headplot displays gamma power during eyes closed in misophonia (8a), the top right for OCD (8b). The bottom left illustrates gamma power during the oddball task in misophonia (8c), the bottom right for OCD (8d). Misophonics expressed a stronger gamma activity during eyes closed in the frontal-central and occipital-parietal regions. During eyes open resting state, gamma power was determined greater for misophonia in the right frontal-central area.
Theta Activity
Theta activity during eyes closed resting state displayed a significantly greater theta activity in misophonia, in each region of interest: FC1, FC2, FCz, CP1, CP2, PO3 and PO4 at a false discovery rate of 10 %; all corrected p-values < .10 (see figure 9a and 9b, table 4a). On the other hand, the degree of symptom severity did not disturb theta activity during eyes closed; all corrected p-values > .10 (see table 4b).
In contrast to a greater degree of theta activity during eyes closed, no significant discrepancies in degree of theta oscillations manifested during the oddball task between
misophonia and OCD; all corrected p-values > .10 (see figure 9c and 9d, table 4a). Group effects for symptom dimensions during the oddball task were, however, significant for the channels FC1, FC2, FCz, CP1 and CP2; all corrected p-values < .10 (see table 4b).
Specifically, these results showed that misophonics exhibit an increased theta activity over OCD patients when resting with their eyes closed, whereas no discrepancies were objectified during the oddball task. The results suggest, furthermore, that theta power is significantly higher for patients who experience mild symptoms than patients suffering severe symptoms during an oddball task, but not eyes closed.
THETA OSCILLATORY POWER AND SYMPTOM DIMENSIONS - GROUP AVERAGES AND P-VALUES
Mild Misophonia Severe Misophonia P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task FC1 28.39 ± 3.38 26.54 ± 2.44 26.86 ± 5.03 22.61 ± 2.99 0.336 0.001* FC2 28.54 ± 3.24 26.68 ± 2.44 27.09 ± 5.14 23.24 ± 2.87 0.357 0.002* FCZ 28.90 ± 3.25 27.32 ± 2.30 27.51 ± 4.83 23.75 ± 3.12 0.360 0.002* CP1 28.10 ± 3.10 26.14 ± 1.95 26.46 ± 5.42 23.15 ± 2.67 0.307 0.002* CP2 27.72 ± 3.43 25.83 ± 2.40 26.39 ± 5.33 22.92 ± 2.82 0.419 0.008* PO3 27.19 ± 3.69 24.89 ± 1.96 26.71 ± 4.17 23.19 ± 2.24 0.749 0.046 PO4 26.41 ± 4.20 24.41 ± 2.25 26.19 ± 4.72 22.50 ± 2.99 0.896 0.067 Table 4a and 4b. Group effects and statistical values for one-way ANOVAs and t-tests on
theta power during each task and symptom dimensions. Theta power was examined during eyes closed and the oddball task. In table 4a the group effects and statistical values of the differences in theta power between groups are depicted for each channel and task by one-way ANOVA. Table 4b presents the group effects and statistical values of the differences between mild and severe misophonia in theta power for each channel and task by Student’s t-test. * Indicates a significant difference between groups at a false discovery rate of 10 %.
THETA OSCILLATORY POWER - GROUP AVERAGES AND P-VALUES
Misophonia OCD P-values
CHANNEL Eyes Closed Oddball Task Eyes Closed Oddball Task Eyes Closed Oddball Task FC1 27.63 ± 3.55 25.41 ± 3.18 25.31 ± 4.76 24.93 ± 3.17 0.006* 0.467 FC2 27.76 ± 3.44 25.55 ± 3.12 25.75 ± 4.53 25.17 ± 3.33 0.014* 0.569 FCZ 28.15 ± 3.33 26.09 ± 3.11 25.83 ± 4.70 25.58 ± 3.07 0.005* 0.434 CP1 27.23 ± 3.61 25.01 ± 2.68 25.05 ± 4.38 24.10 ± 3.41 0.009* 0.143 CP2 27.10 ± 3.63 24.83 ± 2.89 25.05 ± 4.52 24.04 ± 3.50 0.014* 0.232 PO3 26.47 ± 3.37 24.19 ± 2.42 24.32 ± 4.79 23.14 ± 2.95 0.010* 0.058 PO4 26.16 ± 3.65 23.86 ± 2.81 24.33 ± 4.93 23.18 ± 3.13 0.035* 0.269
Figure 9a-d. Theta power expressed during eyes closed (n= 65 vs. n = 36), eyes open (n= 18 vs. n = 4) and oddball task (n= 61 vs. n = 37) for misophonia and OCD. The top left headplot displays theta power during eyes closed in misophonia (9a), the top right for OCD (9b). The bottom left illustrates theta power during the oddball task in misophonia (9c), the bottom right for OCD (9d). Misophonics expressed a stronger theta activity during eyes closed resting state in all selected regions, i.e. frontal-central, central-parietal and occipital-parietal.
Confounding Factors
All confounding factors were explored similarly as oscillatory response and were thus compared at a false discovery rate of 10 %. ERP-activity did not correlate to symptom
dimensions on any questionnaire by any means. A-Miso-S, HAM-A, SIAS and IES-R scores did not correlate to any ERP-activity, in any region of interest, all p-values > .10.
Despite the clear disparity in brain activity between mild and severe misophonia, significant correlations have not been discovered between any of the brain frequencies and A-Miso-S scores; all p-values > .10. Likewise, HAM-A symptom dimensions did not correlate to any power during continuous measuring of the participants. On the other hand, correlations between alpha, beta, theta and gamma power and SIAS-score emerged during continuous measuring for misophonics, but not for OCD patients; p-values < .10 (see appendix A). While the SIAS was discovered to show weak positive correlations with brain activity in misophonia, the IES-R scores manifested into weak negative correlative factors for mostly OCD patients; again all p-values < .10 (see appendix A). Several single channel negative correlations were found between A-Miso-S scores and gamma power with an rpb between -0.500 and -0.300; p-values < .10 (see appendix A).
The majority of the OCD patients (n = 33, 78.6 %) used medication versus merely 8% medication usage among misophonics (n = 5). No differences in ERP and oscillatory responses have been identified among medication status and between medication category; all corrected p-values > .10 at a false discovery rate of 10 %.
Discussion
The discussed data reveal greater ERP responses for N1, MMN and P3 for misophonia than OCD. These findings are partly in strife with the first hypothesis, namely if misophonics display a diminished N1 over OCD patients. The N1-amplitude in misophonia was found to be increased, not attenuated, whereas the MMN was certainly greater for misophonia. The P3 was also displayed to be significantly greater in misophonia, and thus converges with the hypothesis. Though the findings for MMN and P3 are conform the first objective and complementary hypotheses, the findings regarding N1 are not and thus the hypothesis is rejected for N1. The
results furthermore revealed that alpha, beta, gamma and theta oscillations each were stronger in misophonia, whereas this effect was not found during the oddball task between groups. While the hypotheses predicted a diminished alpha power and similar gamma power between misophonia and OCD, the results depicted significant both an increased alpha and gamma activity and thus the second hypothesis is rejected. Symptom dimensions, on the other hand, showed an interesting pattern. While no significant distinctions were detected between ERP response and symptom dimensions - alpha, beta and theta oscillations were each observed to be stronger during the oddball task for mild symptomatology rather than severe symptomatology. These effects comply with the hypothesis, i.e. that symptom dimensions negatively affect neural oscillations.
The foremost limitation of the current study is that participants occasionally have
participated in a neurocognitive assessment prior to undergoing EEG. Mental fatigue is found to increase brain activity such as alpha and theta power, whereas it induces a reduction in N1-amplitude (Boksem et al., 2005). Mental fatigue may therefore have precipitated bias into the data. The study, furthermore, examined OCD patients as a substitute for healthy controls, although OCD patients have demonstrated effects that are well documented and they show similarities to misophonia symptom-wise. By using the OCD patients as a control group, we aimed to unveil the unknown similarities and distinctions between misophonia and OCD. These findings cannot, however, fully explain the differences between misophonics and healthy individuals. One limitation might be that patients are not tested for any auditory impairment. Patients may not have been able to hear the aural stimuli properly, resulting in perhaps a less distinctive EEG and ERP signal. An additional plausible limitation is the inability to identify potential effects between specific deviant stimuli, as the oddball task consists of two tones: a standard and deviant tone, instead of two deviant tones. If the deviant tone will evoke the desired
response, therefore remained unknown. The current experimental setup, namely, used speakers to transmit the aural stimuli, whereas usually the tones are transmitted through a headset during an oddball task. Due to the current study’s nature regarding the neural oscillations, i.e. an
explorative study, the relationship between altered brain activity and the hypersensitivity towards trigger sounds cannot be fully elucidated.
The presented significant findings may be induced by inter-individual differences such as SIAS-score for misophonia, or IES-R scores for OCD as both social anxiety and posttraumatic stress were observed to affect brain activity in misophonia and OCD respectively.
Furthermore, the P3 held several negative values for averages, despite both being a positive component. Such peculiarities might be the result of, for example, converging alpha activity and the ERP-signal, boosting or extinguishing the signal. Alternatively, differing onset-latencies for each component could have potentially induced a relatively low average as we defined rigid time windows; hence several averages were closer to zero or weaker than expected. In addition, the successive presentation of the aural stimuli occurred swiftly during the oddball task, which might have compromised the ERP quality. While the ERP for the earlier stimulus was still recording, the later stimulus was already presented, inducing an odd shift towards the positivity for the average ERPs. The average power of the ERPs therefore might have inclined towards more positive values.
The discussed results concerning symptom dimensions are fairly contradictory with the findings regarding misophonia in general. Severe misophonics were detected to express
diminished oscillatory responses, in comparison to mild misophonia, whereas misophonia’s group averages inclined towards values corresponding to patients suffering mild misophonia and thus differed significantly from OCD. The inclination could be caused by a lack of statistical
power, as the misophonia group comprised of 79 patients, yet A-Miso-S data of 28 patients was available (nMild = 16; nSevere = 12). An alternative explanation for this phenomenon could be that the entire misophonia group experienced mild symptomatology to a greater degree rather than severe symptomatology. Again, no data on this were readily available to analyse such effects properly.
The majority of the OCD patients used medication (76.8 %) versus a minority of misophonia patients (8 %). While no differences were objectified between medication status or medication type, medication could potentially alter brain activity, as the groups were
undoubtedly diverse; n < 3 for most groups using medication such as antidepressants, antipsychotics or anxiolytics or a any combination these drugs.
Lastly, the detected gamma activity was cut off at 45 Hz due to applying a zero-phase FIR filter of 1 to 45 Hz. Gamma power is typically detectable between 30-100 Hz, which may have rendered the observed gamma oscillatory response less distinctive. Moreover, the absence of diminished ERP and oscillatory responses in misophonia might be explained by the fact that the aural stimuli did not trigger the patients successfully to induce symptomatic behaviour, as the aural stimuli were completely dissimilar to trigger sounds. Kumar et al. (2017) examined the extent of stimuli type and discovered that regular annoying sounds, such as babies crying or nails scratching on a blackboard, do not activate certain brain areas such as the AIC. They suggested that solely exposure to trigger sounds induce the specific pathways in misophonia.
The observed effects may have been biased by the fact that OCD patients do display an E/I imbalance. The E/I imbalance is shown to attenuate ERP response such as N1 and MMN (Billingslea et al., 2014; Cooray et al., 2014; Gandal et al., 2012), which might have led to a false positive finding regarding the increased N1 and MMN in misophonia. Likewise, prior research
has shown that the E/I imbalance in OCD diminished neural oscillatory responses such as gamma frequency (Gandal et al., 2012; Yizhar et al., 2014). The E/I imbalance is therefore also likely to have caused the group effects of gamma activity to differ significantly during eyes closed resting state.
To conjecture, the stronger N1-amplitude in misophonia could suggest an increased ability to detect abrupt acoustic changes; which allows an individual to better tend to informative stimuli (Näätänen, 1992; Rinne et al., 2006; Winkler, 2007). This heightened ability might clarify how misophonics are hypersensitive towards trigger sounds, as they might perceive specific aural events stronger than healthy individuals. However, the obtained results, regarding N1, are in conflict with the results of prior studies. The current study revealed a significantly greater N1-amplitude in misophonia than OCD, instead of an expected attenuation of N1 according to prior research by Schröder et al. (2014). To conjecture this discrepancy, OCD patients were found to solely have a longer N1 latency than healthy patients (Morault et al., 1997; Di Russo et al., 2000), thus raising the suggestion that the N1-amplitude is similar to that of healthy individuals. The results presented by this study thus seem to be at discord in terms of regular brain activity and ERP response and following assessment for symptom dimensions. No explanation could fully elucidate why we observed an increased N1, though it might portray a heightened early perception of specific aural events.
Furthermore, the larger MMN response may suggest an increased attention allocation towards specific sensory cues, as the MMN is thought to reflect attention allocation to deviating situations (Näätänen, 1992; Rinne et al., 2006). The tendency to allocate more resources to trigger sounds might elucidate a possible factor for the hypersensitivity towards the trigger sounds. The increased P3 response may depict a deflection of the misophonia patient’s ability to
become mentally aware of the sound (Picton, 1992) and to generate appropriate responses (Linden, 2005). As presented by Yamamuro et al. (2016) that OCD patients elicit an attenuated P3, this has likely affected the significant distinctions between misophonia and OCD.
Misophonia patients might, therefore, have a typical P3 component.
To conjecture if the increased N1, MMN and P3 indeed reflect early sound processing, attention allocation and consciousness respectively, they could expose plausible sources for the hypersensitivity typically observed in misophonics. The increased early perception of aural stimuli, in combination with a greater attention allocation to and awareness of a trigger sound, and perhaps with high levels of moralism typically found in OCPD symptomatology, might explain why misophonia patients experience an extreme sensitivity towards certain sounds. The increased alpha power in misophonia could potentially identify a source for the hypersensitivity towards trigger sounds. Possibly in misophonia, the baseline alpha activity is higher than in healthy individuals, which may suggest a greater urgency for alpha oscillations to suppress incoming signals. If the alpha activity were to be diminished due to severe
symptomatology, as is revealed by the results, the brain may become less competent at filtering incoming stimuli.
Furthermore, it is suggested that misophonics express a typical E/I balance, as gamma power during resting state was greater for misophonia than OCD. Namely, a greater gamma power implies more inhibition, whereas OCD patients revealed an impaired E/I balance in prior research, indicating a lower amount of gamma oscillations (Leyfer et al., 2006; Richter et al., 2012). Given the fact that misophonics express a typical E/I balance, the results are at discord with prior research by Kumar et al. (2017), wherein they discussed that misophonia is caused by the wrongful processing of otherwise harmless sounds. The detection of abnormal interoceptive
processes lie beyond the capabilities of EEG and requires the assessment of internal body states and connectivity between brain areas, as EEG solely measures cortical activity in this type of setup.
The increased beta activity in misophonia could indicate a greater need for suppression of movement, or perhaps that misophonia patients could better resist their movement urges than OCD patients (Zhang et al., 2008). Why an amplified beta activity was observed can only be partly explained by the fact that participants were instructed to remain motionless during the assessments. This, however, cannot be linked to the psychopathology and symptomatology of misophonia. Likewise, the augmented theta activity in misophonia patients during eyes closed is barely of any relevance to the main findings and they explain no critical role. If theta oscillations contribute at all to the symptomatology of misophonia, the relationship between misophonia and increased theta activity remains difficult to elucidate.
The extent of overlap in symptomatology between misophonia and multiple disorders is reinstated by the fact that misophonia also overlaps with SOR. Alike SOR patients, misophonics tend to over respond to specific aural cues. The increased N1, MMN and P3 might possibly play part in the overly sensitivity of misophonics, if they indeed reflect an enhanced early sound processing, attention allocation and awareness of aural stimuli.
Alternatively, the increased N1, MMN and P3 could potentially be attributed to the fact that misophonia might be based on negative emotions to traumatic events. Negative emotions and memories are typically hardwired into our brains, to prevent us from experiencing a similar event anew. Plausibly, the increased N1, MMN and P3 could be the result of an increased hardwiring towards these negative events, or in this case the trigger sounds and their associations, to prevent the misophonic from being in a distressing situation.
Examining the neural mechanisms that induce misophonia is crucial, as they currently remain unknown. More insight on the underlying neurobiological mechanisms could grant misophonia patients more understanding of their disorder, if indeed it can be classified as a stand-alone disorder. The discussed findings will hopefully complement the RDoC regarding cognitive systems posed by the NIMH and contribute to clearer research in the field of psychiatric disorders. The presented results might provide supplementary information about misophonia, allowing the possibility to decide whether misophonia can be classified as a stand-alone disorder as misophonia research is still in its infancy.
As a concluding remark, misophonics evoke increased N1, MMN and P3 responses in comparison to OCD patients, and elicit a greater degree of alpha, beta, theta and gamma
oscillations during eyes closed resting state and an oddball task. Increasingly severe misophonia symptoms attenuate the oscillatory, but not ERP response. The current study was aimed to expose a contributing factor in the symptomatology of misophonia, as misophonia is likely to be the product of malfunctioning of both psychological and neurobiological processes. To entirely identify the ambiguous symptomatology and underlying neurobiological processes, more extensive research is required. Future research should first delineate whether misophonia is a stand-alone disorder, then assess ERP and neural oscillatory response during exposure to real trigger sounds in comparison to healthy individuals.
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