Altered visual repetition suppression in Fragile X Syndrome: New evidence from ERPs and oscillatory activity

Abstract

Fragile X Syndrome (FXS) is a neurodevelopmental genetic disorder associated with cognitive and behavioural deficits. In particular, neuronal habituation processes have been shown to be altered in FXS patients. Yet, while such deficits have been primarily explored using auditory stimuli, less is known in the visual modality. Here, we investigated the putative alteration of repetition suppression using faces in FXS patients compared to controls that had the same age distribution. Electroencephalographic (EEG) signals were acquired while participants were presented with 18 different faces, each repeated ten times successively. The repetition suppression effect was probed by comparing the brain responses to the first and second presentation, based on task-evoked event-related potentials (ERP) as well as on task-induced oscillatory activity. We found different patterns of habituation for controls and patients both in ERP and oscillatory power. While the N170 was not affected by face repetition in controls, it was altered in FXS patients. Conversely, while a repetition suppression effect was observed in the theta band (4-8Hz) over frontal and parieto-occipital areas in controls, it was not seen in FXS patients. These results provide the first evidence for diminished ERP and oscillatory habituation effects in response to face repetitions in FXS. These findings extend previous observations of impairments in learning mechanisms and may be linked to deficits in the maturation processes of synapses caused by the mutation. The present study contributes to bridging the gap between animal models of synaptic plasticity dysfunctions and human research in FXS.

Integrative cross-species analyses identify deficits in habituation learning as a widely affected mechanism in Autism

“…A decreased ability to habituate has been described in a fraction of ASD individuals (9–11), but has not been connected yet to specific genetic defects, with a single exception. Recently, two independent studies demonstrated habituation deficits in patients with Fragile X syndrome, the most common monogenic cause of intellectual disability (ID) and ASD (12, 13), confirming previously reported habituation deficits in Fmr1 KO mice (14, 15). Habituation deficits have also been reported in a limited number of other ID or ASD (ID/ASD) disease models (16–19).…”

“…Still, this latter phenotype category can result from other defects than improved habituation, and will be investigated elsewhere. In this study we focus on habituation deficits (3), corresponding to the phenotype that has been shown in ID and ASD (9–13).…”

“…If future work can establish a substantial contribution of deficits in habituation learning to patient outcomes, cross-species habituation could become an attractive mechanism-specific functional readout—a pressing need for efficient personalized (pharmacological) treatment in the field of neurodevelopmental disorders. Implementing suitable low-burden protocols for habituation measures in clinical research and diagnostics of ID/ASD, such as those developed for investigation of habituation deficits in Fragile X syndrome (12, 13), will help to further delineate the affected cognitive domains that may correlate with or arise from deficient habituation. In future clinical trials, these could serve as objective and quantitative readouts for patient stratification in mechanism-based treatment strategies and for monitoring of drug efficacy.…”

Additive effect of contrast and velocity proves the role of strong excitatory drive in suppression of visual gamma response

“…Gamma synchronization facilitates neural communication and increases the effective output of presynaptic (Bastos et al, 2015; Fries, 2005, 2009, 2015; Ni et al, 2016; Rigoulot et al, 2017; Vinck et al, 2013). Therefore, synchronization of V1 neural activity in the gamma range is thought to enhance the effective output from the primary visual cortex to upstream cortical areas, thus affecting visual perception.…”

Neural gain control measured through cortical gamma oscillations is associated with individual variations in sensory sensitivity

“…Recent advances in genetics and neuroscience clearly demonstrate that behavioral symptoms of ASD and other neurodevelopmental disorders may stem from cardinally different genetic and molecular etiologies that cause either increases or decreases in the E/I ratio (Lee et al, 2017; Nelson and Valakh, 2015). Given the heterogeneous nature of ASD (Gillberg, 2010; Jeste and Geschwind, 2014; Tordjman et al, 2018), the abnormal capacity to regulate the E/I balance in the visual cortex could characterize only a proportion of ASD individuals, as well as, e.g., patients with fragile X syndrome who are often hypersensitive to visual stimuli and are suggested to have elevated neural excitability of the visual cortex (Rigoulot et al, 2017; Schneider et al, 2009; Sinclair et al, 2017; Van der Molen et al, 2012). Considering the reliable correlation between sensory sensitivity and GSS (Fig.…”