Background. Parkinson’s disease (PD) patients are at increased risk for central auditory processing (CAP) deficits and cognitive dysfunction. However, behavioral assessments of CAP and cognitive processing used in a previous study by our research team found few significant differences in performance between early-stage PD patients and age-matched control subjects. The objective of this study is to use auditory event-related potentials (AERPs) to compare CAP and cognitive functions in a population of PD patients with a group of age-matched control subjects. Methods. AERPs in response to tonal and speech stimuli were recorded from 35 adults who had a medical diagnosis of PD (23 males and 12 females; ), and 35 age-matched control subjects who did not have PD or any other neurological disorders (31 males and 4 females; ). Auditory stimuli included pure tones (500 and 1000 Hz) to elicit the P300 response and a dichotic digits paradigm to elicit the N200 processing negativity. Results. Compared to control subjects, PD patients exhibited significantly longer latencies of P300 and N200 components and smaller amplitude N200 components. Latency and amplitude of the N200 component were significantly correlated with participants’ age. N200 amplitude was correlated with results from the Rey Auditory Verbal Learning Test (RAVLT) of cognitive ability. Latency of the P300 and amplitude of the N200 components were significantly correlated with results from the Spatial Release From Masking (SRM) behavioral CAP assessment. Conclusions. AERP assessments used in this study appear to be sensitive indicators of CAP and cognitive deficits exhibited by early-stage PD patients. While few significant differences in performance on behavioral CAP and cognitive tests were previously observed between this population of PD patients and age-matched control subjects, N200 and P300 components recorded in the present study revealed impaired neural processing by the PD group.
Aging and hearing loss both contribute to declines in one’s ability to process auditory information. For example, older people and those with hearing loss often have difficulty understanding conversational speech when background noise is present [1–3]. The average patient age for Parkinson’s disease (PD) onset is approximately 60 years, and the prevalence of PD increases with age . Since the majority of people 60 years old and older have significant hearing loss (HL), and the prevalence of HL increases with age [5, 6], a majority of PD patients have significant HL that will worsen over time. Patients with untreated hearing loss dedicate more of their resources to auditory perceptual processing to the detriment of other cognitive processes. Therefore, hearing loss may contribute to dementia through exhaustion of cognitive reserves, social isolation, sensory deafferentation, or a combination of these mechanisms . Since cognitive decline and dysfunction are common sequelae of PD , untreated hearing loss is likely to exacerbate cognitive deficits that are experienced by many PD patients.
Guehl et al. , Lewald et al. , and Vitale et al.  reported that PD patients exhibited poorer performance on behavioral assessments of auditory processing compared to groups of age-matched, healthy control subjects. Therefore, the neuropathological mechanisms of PD appear to contribute to central auditory processing (CAP) deficits in this population . A previous study by our research group also reported abnormal performance by a group of PD patients on behavioral CAP tests . However, because most of these PD patients were in the early and less severe stages of disease, their performance on many CAP assessments did not differ significantly from that exhibited by a group of age-matched healthy control subjects.
The goal of the present study was to use auditory event-related potentials (AERPs) to assess CAP and cognitive functions in a population of PD patients and compare the results with a group of age-matched control subjects without PD or other neurological disorders. We hypothesized that electrophysiological recordings are more sensitive detectors of auditory and cognitive processing deficits exhibited by PD patients than are the behavioral assessments used in our previous study .
All procedures for the conduct of the study adhered to the requirements of the Institutional Review Board at VA Portland Medical Center, where the study was conducted.
Participants included 35 adults who had a medical diagnosis of PD and 35 age-matched control subjects who did not have PD or any other neurological disorders. All of the participants in this study were the same as those in our 2017 publication . Also, the electrophysiological data reported in this article were collected around the same time as behavioral data previously reported for this population .
After written informed consent was obtained, participants underwent the procedures and assessments described below over the course of three sessions.
2.1. Assessments of PD Severity
The Hoehn and Yahr  and Schwab and England  scales were used to assess the stage and severity of PD for individuals in the patient group.
Parkinson patients were also asked to rate their abilities “during the past week” for 12 activities such as swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (these questions were taken from Part II of the Unified Parkinson’s Disease Rating Scale ).
2.2. Neuropsychological Evaluation
The Rey Auditory Verbal Learning Test (RAVLT)  was administered to all study participants. This test evaluates a variety of functions: short-term auditory-verbal memory, rate of learning, learning strategies, retroactive and proactive interference, presence of confabulation or confusion in memory processes, retention of information, and differences between learning and retrieval. Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat them. Another list of 15 unrelated words is given, and the subject must then repeat the original list of 15 words; this process is repeated again 30 minutes later.
2.3. Comprehensive Audiometric Evaluation
Pure tone air and bone conduction thresholds were measured in each ear using procedures recommended by the American Speech-Language-Hearing Association .
2.4. Assessments of Central Auditory Processing (CAP)
Several different CAP evaluations were administered to study participants: Staggered-Spondaic-Word (SSW) test , Masking-Level Difference (MLD) Test [19, 20], Gap in Noise (GIN) Detection Test , Dichotic Digits Test , Spatial Release From Masking (SRM) tests , and Speech Intelligibility in Noise was assessed using the Words in Noise (WIN) test . These tests are described in our previous publication involving this study population .
2.5. Electrophysiological Recordings of Auditory Event-Related Potentials (AERPs)
Long-latency AERPs were recorded from 15 Ag/AgCl scalp electrodes using a Quik Cap and a Neuroscan EEG/EP system (Compumedics, Charlotte, NC) according to parameters described in Papesh et al. . Responses to 50 repetitions of each stimulus were averaged to create individual responses within each condition. Grand average responses were created for each condition and group.
Latency and amplitude values of N100, P200, N200, and P300 components were determined by the agreement of the three judges. Long-latency AERPs were recorded from each subject in response to the following stimuli which were presented via Etymotic ER-3 insert earphones (Etymotic Research, Inc.; Elk Grove Village, IL).
2.5.1. “Oddball” Paradigm (Tones) to Elicit P300 Responses
Stimuli: 50 1000-Hz tones (100 msec duration) and 200 500-Hz tones (100 msec duration) were presented in a randomized sequence at 85 dB SPL to each ear monaurally; . Task: subjects counted higher-pitched (1000 Hz) tones silently to themselves. This electrophysiological protocol provides an objective measure of central auditory processing and cognitive function.
2.5.2. Dichotic Digits
Stimuli: an assortment of 300 spoken digits (50 each: 1, 2, 3, 4, 5, or 6) delivered dichotically and presented randomly. Task: subjects pushed a button with their right index finger when they heard the target “four” in either ear. Because a study by Lewald et al.  reported that PD patients exhibited deficits in behavioral dichotic listening tasks, this electrophysiological protocol was included to provide an objective measure of neural processing and cognitive function during such a task.
2.6. Data Analysis
Mean and standard deviation values were calculated for each assessment, AERP component, and study group. Between-group comparisons were conducted using 2-tailed -tests and applying appropriate Bonferroni corrections as needed. Pearson correlation calculations were also made in certain instances as indicated in the Results section. Tests of normality and homogeneity of variances confirmed the statistical appropriateness of these analyses for the data collected.
3.1. Participant Characteristics
The PD group consisted of 35 adults (23 males and 12 females; ). The control group also consisted of 35 adults (31 males and 4 females; ) who had no history of PD or other neurological disorders. The difference in the proportion of males vs. females in each of the study groups was statistically significant (). Levodopa use by PD patients: all PD patients except one used levodopa medication daily—he had not yet started using this medication. Of 105 total appointments, PD patients reported that they were “on” the effects of levodopa for 95 appointments, “off” for 7 appointments, and “in-between” for 3 appointments.
For additional details about participant characteristics, see our previous publication involving this study population .
3.1.1. Ratings of Daily Activity Abilities
For PD patients in this study, the total score on these 12 questions ranged from 3 to 27 (), with higher scores indicating greater difficulty on the collection of tasks. These data, combined with Hoehn and Yahr and Schwab and England results, suggest that the majority of PD patients in this study were in the early—or less severe—stages of the disease.
3.2. Neuropsychological Evaluation
Mean RAVLT scores (total of trials 1 through 5) were for PD patients and for control subjects, which indicates normal performance for the age and education level of study participants . The difference in mean scores between study groups was not statistically significant. Also, there was no statistically significant difference in the number of intrusions or repetitions made by the two study groups on this test.
3.3. Pure Tone Audiometry
Pure-tone audiometry indicated that both the control and PD groups had sloping, high-frequency sensorineural hearing loss which is typical for their age range (see Figure 1 in Folmer et al. ). Compared to age-matched healthy control subjects, PD patients exhibited worse hearing sensitivity for 1500 and 2000 Hz test frequencies. Pure tone average (PTA) threshold was HL for the control group and HL for the PD group.
We subdivided study participants into younger (≤65 years) and older (>65 years) groups according to age criteria used by da Silva Lopes et al. . This grouping resulted in 19 younger () and 16 older () control subjects; 17 younger () and 18 older () PD patients. In general, hearing sensitivity for older participants (older controls = OC; older Parkinson = OP) was worse compared to younger participants (younger controls = YC; younger Parkinson = YP), especially for higher frequencies. Pure tone hearing thresholds did not differ significantly between the OC and OP groups. However, the younger PD group exhibited worse hearing between 1500 and 2000 Hz compared to the younger control group. This difference was the major contributor to overall differences in hearing sensitivity between the entire PD and control groups.
3.4. Assessments of Central Auditory Processing
As reported in our previous publication involving this study population , both study groups exhibited deficits in many assessments of central auditory processing (CAP), with PD patients performing significantly worse than the control group on the Spatial Release from Masking (SRM) 45° test condition only. Compared to the control group performance on the SRM test, the PD group had greater difficulty understanding sentences in a background of competing speech, and they also showed less improvement on this task when the target and competing sentences were separated in space (the 45° condition).
3.5. Electrophysiological (AERP) Results
3.5.1. “Oddball” Protocol to Elicit the P300 Response
As shown in Figure 1, AERP grand averaged responses to the “nontarget” 500 Hz tones (recorded at electrode Cz) were basically the same for PD patients and control subjects. The latency and amplitude of the N100 component are not significantly different between the study groups. However, the mean latency of the P300 component in response to the “target” 1000 Hz tones was significantly delayed () for PD patients () compared to control subjects (). There was no statistically significant difference in P300 amplitude between the PD and control groups.