Differential sensory fMRI signatures in autism and schizophrenia: Analysis of amplitude and trial-to-trial variability

Abstract

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d<0.29). These differential group profiles suggest (1) that greater trial-to-trial variability in cortical responses may be specific to autism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders.

Variable sensory perception in autism

“…In vision, it is generally accepted that low‐level/early visual processing is intact and similar to controls. For example, visual acuity (Kéïta et al ., ; Falkmer et al ., ; Tavassoli et al ., ), contrast detection and discrimination (Haigh et al ., ), visual shape orientation, and flicker detection are all within the normal range. However, individuals with autism show superior performance on local, detail‐focused tasks, and poorer processing for more holistic or global processing.…”

“…To verify that individuals with autism are not better able to share their attention than controls, attention‐switching abilities were measured (Haigh et al ., ). Most of the autism group who participated in the following attention‐switching study also participated in the fMRI studies described above.…”

Atypical neural variability in carriers of 16p11.2 copy number variants

“…Atypical neural variability has been shown in several diagnoses including ASD [Milne, ; Dinstein et al, ; Weinger et al, ; Edgar et al, ; Haigh et al, , ; but see Coskun et al, ; and Butler et al, ], attention deficit hyperactivity disorder (ADHD) [Woltering, Jung, Liu, & Tannock, ; McLoughlin, Palmer, Rijsdijk, & Makeig, ; Gonen‐Yaacovi et al, ; Sørensen, Eichele, van Wageningen, Plessen, & Stevens, ], and schizophrenia [Shin et al, ; Haigh et al, ]. Interestingly, all of these conditions are associated with 16p11.2 CNVs [Williams et al, ; Sanders et al, ; Snyder et al, ; Marshall et al, ].…”

“…Because there are many variables that have been suggested to indicate neural variability [e.g., Milne, ; Weinger, Zemon, Soorya, & Gordon, ; Haigh et al, ; Arazi et al, ; Butler, Molholm, Andrade, & Foxe, ], it is good practice to apply more than one measure and examine whether there is concordance between the metrics. Measures of neural variability examined in the current study were C1, P1, and N1 variability; intertrial variability in ERP amplitude across the timecourse (timecourse variability); alpha and beta power variability; and EEG SNR.…”

Explorations and perspectives on the neurobiological bases of autism spectrum disorder

“…Basic sensory‐perceptual anomalies are a recurrent theme in ASD and lend themselves very well to investigation with current neurophysiological and neuroimaging techniques. Here, a set of studies report on such diverse processes as auditory spatial processing, pain anticipation, and error registration (Gu et al ., ; Kim et al ., ; Lodhia et al ., ), and an opinion piece by Sarah Haigh of the University of Pittsburgh presents evidence both for and against what we call the ‘neural unreliability’ hypothesis, the notion that initial cortical sensory responses to repeated events are more variable across trials in ASD (Dinstein et al ., ; Haigh et al ., , ; Butler et al ., ; Haigh, ).…”