 participants with high-functioning autism and typical development.
What are the implications of the feasibility findings? Our findings confirm the feasibility and potential utility of including individuals with LFA in evoked potential studies of visual processing in autism.
Visual processing abnormalities are considered common in autism spectrum disorder (ASD), a complex neurodevelopmental disorder characterized by impaired social interaction and communication and stereotyped behaviors and interests [1]. Despite considerable research, there are no known electrophysiological markers of atypical visual processing in individuals with ASD. One impediment has been the challenge of testing individuals from across the ASD spectrum and, in particular, individuals with low-functioning autism (LFA) who are often unable to adhere to the behavioral demands of traditional visual evoked potential paradigms or behavioral and neuroimaging studies in general [2, 3]. Individuals with LFA, also referred to as ASD level-3 based on DSM-5 criteria [1], typically have more severe ASD features, including minimal verbal skills and inability to function independently in daily living. LFA is one of two widely used classifications for individuals with ASD. The other is high-functioning autism (HFA), also referred to as ASD level-1 [1], which refers to individuals who are moderately to highly verbal and require minimal or no support for daily living.
Evoked potential studies based on passive stimulus paradigms have been used successfully to investigate sensory processing across the autism spectrum, including auditory and somatosensory processing [4,5,6,7]. However, passive visual stimulus paradigms can be challenging to implement with individuals with LFA because they must be visually attending whenever stimuli are presented in order to elicit evoked responses.
To address the methodological challenges of conducting visual evoked potential studies with individuals with LFA, we explored the feasibility of using a hybrid visual paradigm that combines passively presented stimuli to elicit evoked potentials with a different set of stimuli in a visual task to ensure participants are visually attending when passive stimuli are presented. Feasibility was assessed based on study completion rates and quality of recordings. We then conducted a pilot study that included two additional groups—individuals with high-functioning autism (HFA) and individuals with typical development (TD)—to investigate potential patterns of cortical visual activity that may be specific to individuals with LFA, based on evoked responses and spectral (oscillatory) power measurements.
A total of 18 individuals, ages 17–48 years (15 males, 3 females), participated in the study. Participants were assigned to one of three groups (Table 1), each with six participants (5 males, 1 female): an LFA group, an HFA group, and a TD group. The diagnosis of autism was based on physician diagnoses, as confirmed by participants’ medical records and DSM-5 criteria [1], and scores of ≥10 on the Autism Diagnostic Observation Schedule Second Edition (ADOS-2) [8]. The mean age of participants with ASD was 29.8 years ±9.0; the mean age of participants with TD was 26.0 years ±4.8.
Participants with ASD were classified as LFA or HFA based on the level of support required for daily living and on verbal communication abilities. Individuals classified as LFA required full support for daily living and were either nonverbal or minimally verbal; individuals with HFA required little or no support for daily living and demonstrated good verbal language abilities, including spontaneous speech production. To further assess language and cognitive function, all ASD participants completed the Peabody Picture Vocabulary Test and all but one ASD participant were also administered the Kaufman Brief Intelligence Test-2 (Table 1). The one exception was a participant with LFA (P1_LFA) who was unable to follow test directions to perform the Kaufman Brief Intelligence Test-2.
ASD participants were recruited through educational programs and a local institution that provides day services to individuals with autism and other developmental disorders. ASD and TD individuals were also recruited through newspaper advertisements and fliers posted at regional academic centers. Individuals were excluded from participation if they had a history of neurologic disease (e.g., epilepsy) or substance abuse, vision deficits, or demonstrated excessive movements or an inability to tolerate the electrode net used for the electrophysiology recordings. A total of nine individuals with LFA was originally recruited of whom three were excluded due to excessive movement and/or inability to wear the electrode net. All participants had normal or corrected-to-normal vision based on parental/caregiver reports (LFA) or self-reports (TD, HFA). Informed written consent was obtained from, or on behalf of, all participants: HFA and TD participants provided written informed consent; parents, guardians, or caregivers provided consent for LFA participants. All participants were paid $15 per hour for their participation. All procedures and consent processes were approved by the Institutional Review Board of the Johns Hopkins Medical Institutions.
The experimental set-up was the same for all participants. Each participant was tested individually in a quiet room where they were seated in front of a 34.5 x 27.5 cm LCD computer screen (1280 x 1024 pixel resolution, 60 Hz temporal resolution) with attached computer mouse. Viewing distance from the screen was approximately 50 cm; room lighting was dimmed to enhance visualization of the screen. Data collection was conducted by pairs of trained research assistants (HG, MM, LB) who were experienced in conducting electrophysiology studies with individuals with autism. A senior researcher (KS) with expertise in electrophysiology and signal processing was also present during the recording sessions to assist with the experimental set-up and technical issues and to monitor the recordings.
Based on prior observation that individuals with LFA often show increased agitation in unfamiliar situations, we implemented two familiarization strategies. First, all participants with LFA underwent one or two sessions of net tolerance training during the month prior to the study to familiarize them with wearing the electrode nets. Second, a family member or caretaker was present during testing, and at least one member of each researcher pair was introduced to the participant prior to the date of the study. The participant’s family member or caregiver also helped determine when session breaks were needed during testing.
The main visual stimulus was a static black-and-white checkerboard pattern that appeared as a brief flash (100-ms duration) on the computer screen. The checkerboards were full-screen patterns comprised of 1.83 cm2 squares. A second visual stimulus was a pair of shapes, a white square and a white circle both 8 cm in size (length/diameter), presented side-by-side in the center of the screen. The location of each shape on the left or right side varied randomly across trials. The luminance of the white- and black-colored stimuli on the screen was 140 cd/m2 and 0.3 cd/m2, respectively.
Stimulus trials were presented consecutively with checkerboard trials interspersed randomly among shape-pair trials. The trial structure was the same for both stimuli. Each trial began with a blank (black) screen, lasting for 500 ms, followed by a white fixation cross in the middle of the screen for 1000 ms. This was followed by a second blank screen that lasted for 1200 ms, followed by presentation of either a checkerboard stimulus or a shape-pair stimulus. Each trial was followed by a 1000-ms blank screen. All stimuli were presented using E-prime software (version  |||IP_ADDRESS|||, Psychology Software Tools, Inc., Sharpsburg, Pennsylvania) running on a Windows XP PC (Dell OptiPlex 755, Dell Technologies, Round Rock, Texas).
The checkerboard trials were presented passively: no behavioral response was required and participants were not told about them beforehand. Passive presentation of the checkerboard trials controlled for individual differences in attentional states and behavioral performance across participants. The shape-pair trials served to encourage sustained visual attention to the computer screen by engaging participants in a behavioral task. Participants were instructed to respond on shape-pair trials by using the computer mouse to click on the circle shape. Participants with LFA were given verbal instructions, demonstrations, and practice trials before the session. Each pair of shapes remained on the screen until participants responded or until 10 s had elapsed. To ensure that participants moved the mouse to the target shape, the mouse pointer arrow returned to the bottom center of the screen before each trial. Participants’ behavioral responses were recorded online for analysis (accuracy, reaction time).
To minimize the time, the participants were required to sit still and to facilitate breaks during the session, and trials were grouped into five blocks of 108 trials each. Each block contained both visual stimuli in a 5:1 ratio of shape-pair trials to checkerboard trials. For two participants with LFA (P2 and P3), the number of stimulus blocks was increased to 10 (P2) and nine (P3) blocks of 72 trials. By both increasing the number of blocks and decreasing their length, participants could be given more frequent breaks while completing additional trials without extending the duration of the recording session.
Only checkerboard trials were included in the electrophysiology analysis. The total number of checkerboard trials presented to participants ranged from 108 to 140, depending on the number of stimulus blocks administered. For participants with LFA, the average number was 122 checkerboard trials. To verify that participants with LFA were attending to the computer screen when checkerboard stimuli were presented, two high-definition camcorders were used to video record each session: one recorded a frontal face view; the second recorded a rear view, including the computer screen (Sony HDR-CX360, Sony Corporation, NYC, New York).
At the beginning of each recording session, a 256-channel HydroCel Geodesic Sensor electrode net that had been soaked in electrolyte solution (tap water with potassium chloride; 11,000mg/L) was fit onto each participant’s head. The electrode nets remained on for the entire session