The effect of aging, Parkinson's disease, and exogenous dopamine on the neural response associated with auditory regularity processing

Abstract

Processing regular patterns in auditory scenes is important for navigating complex environments. Electroencephalography (EEG) studies find enhancement of sustained brain activity, correlating with the emergence of a regular pattern in sounds. How aging, aging-related diseases such as Parkinson's disease (PD), and treatment of PD affect this fundamental function remain unknown. We addressed this knowledge gap. Healthy younger and older adults, and PD patients listened to sounds that contained or were devoid of regular patterns. Healthy older adults and PD patients were tested twice-on and off dopaminergic medication in counterbalanced order.Regularity-evoked, sustained EEG activity was reduced in older, compared to younger adults. PD patients and older controls had comparable attenuation of the sustained response. Dopaminergic therapy further weakened the sustained response in both groups. These findings suggest that fundamental regularity processing is impacted by aging-related neural changes but not those underlying PD. The finding that dopaminergic therapy attenuates rather than improves the sustained response coheres with the dopamine overdose response and implicates brain regions receiving dopamine from the ventral tegmental area in regularity processing.

The Effect of Parkinson's Disease on Otoacoustic Emissions and Efferent Suppression of Transient Evoked Otoacoustic Emissions

“…In this study, both patients with PD and age-and gender-matched HCs demonstrated a sensorineural age-related hearing impairment, indicated by increased high-frequency auditory thresholds in both groups. Consistent with previous studies (Al Jaja et al, 2020;De Keyser et al, 2019;Di Mauro et al, 2017;Lopes et al, 2018;Richardson & Sussman, 2019), no significant differences were found between patients with PD and HCs regarding auditory thresholds, irrespective of medication condition. In contrast, a number of studies have reported significantly increased auditory thresholds in patients with PD, primarily in the high-frequency range (Al Zarea et al, 2016;Folmer et al, 2017;Hussein & Koura, 2019;Pisani et al, 2015;Scarpa et al, 2020;Shalash et al, 2017;Shetty et al, 2019;Vitale et al, 2016Vitale et al, , 2012Yýlmaz et al, 2009).…”

“…In order to assess the effect of dopaminergic medication on auditory alterations in PD, the same patients with PD were compared in on-and off-medication states. Consistent with previous studies (Al Jaja et al, 2020;De Keyser et al, 2019;Pisani et al, 2015), auditory thresholds were not modulated by patients' dopaminergic medication status or daily LED. Moreover, OAE signal amplitudes did not differ significantly between patients with PD on and off dopaminergic medication.…”

“…A gold standard in the audiological examination and repeatedly studied in PD is pure-tone audiometry, a subjective measure of hearing sensitivity (Musiek et al, 2017). On the one hand, a number of studies did not find significant differences between patients with PD and age-matched healthy controls (HCs) regarding auditory thresholds (Al Jaja et al, 2020;De Keyser et al, 2019;Di Mauro et al, 2017;Lopes et al, 2018;Richardson & Sussman, 2019). On the other hand, studies have reported significantly higher auditory thresholds or a higher prevalence of hearing impairment in patients with PD compared to age-matched HCs, primarily in the high-frequency range (Al Zarea et al, 2016;Folmer et al, 2017;Hussein & Koura, 2019;Pisani et al, 2015;Scarpa et al, 2020;Shalash et al, 2017;Shetty et al, 2019;Vitale et al, 2016Vitale et al, , 2012Yýlmaz et al, 2009).…”

“…As such, dopamine is believed to prevent excitotoxic damage to the auditory afferents as a result of an excessive release of glutamate from the IHCs (e.g., during excessive noise exposure; Fuente, 2015;Lendvai et al, 2011). In PD, the application of dopaminergic medication has not led to significant changes regarding auditory thresholds in previously untreated patients with PD (Pisani et al, 2015) or in patients who discontinued dopaminergic medication (Al Jaja et al, 2020;De Keyser et al, 2019). Second, increased hearing thresholds in PD have been linked to the widespread distribution of alphasynuclein aggregates throughout the central, autonomic, and peripheral nervous systems (Braak et al, 2003;Comi et al, 2014).…”

Neurophysiological investigation of auditory intensity dependence in patients with Parkinson’s disease

“…In turn, dopamine is transmitted from the VTA toward the ventral striatum and prefrontal cortex (PFC) through the mesocorticolimbic projections. Compared to the profound loss of dopaminergic neurons in the SNc from which dopamine is transmitted through the nigrostriatal projections toward the dorsal striatum, a relatively spared ventral striatum has been considered in PD (Al Jaja et al 2020;Cools 2006;MacDonald and Monchi 2011). Since opponent interactions between serotonin and dopamine have been hypothesized, low serotonergic function may imply disinhibition of dopaminergic activity in the ventral striatum and PFC (Daw et al 2002;Kapur and Remington 1996;Seo et al 2008).…”