Atypical responses to sensory stimuli are frequently associated with the neurodiversity observed in autism spectrum disorder (ASD) (Leekam et al., 2007; Tomchek and Dunn, 2007) and can impose lifelong challenges to autistic individuals (Suarez, 2012). Sensory processing symptoms associated with ASD can be very severe and, although heterogeneous in their presentation (Fernández-Andrés et al., 2018; Tillmann et al., 2020), are predictive of both social dysfunction (St. John et al., 2022; Sweigert et al., 2020) and repetitive behaviors (Sweigert et al., 2020). Although sensory differences have not been as well characterized as social impairments, atypical sensory processing has been observed as young as 9 months of age in infants who later develop ASD (Gliga et al., 2015) suggesting that these may emerge concurrently with other social impairment and restricted and repetitive symptoms. Atypical responses to sensory features such as smell, texture, color, temperature, and sound can contribute to food selectivity (Chistol et al., 2018), avoidance of certain play materials, refusal to participate in family activities (Reynolds et al., 2011), and academic underachievement (Ashburner et al., 2008).

Sensory features were reported in the earliest descriptions of autism (Kanner, 1943), yet physiological studies of basic sensory processing in ASD have yielded mixed results (See Robertson and Baron-Cohen (2017) for review). Frequently cited studies have found evidence of sensory enhancement, such as enhanced pitch sensitivity and auditory discrimination (Bonnel et al., 2003), but also, for example, reduced speech-specific tone perception in Mandarin-speaking autistic children and reduced auditory attention deployment in young autistic adults (Wang et al., 2017; Emmons et al., 2022). Studies of tactile processing have found increased sensitivity to vibration (Cascio et al., 2008) and pain (Cascio et al., 2008; Riquelme et al., 2016) abnormal tactile perceptual thresholds (Blakemore et al., 2006; Puts et al., 2014), and higher intensity ratings (Blakemore et al., 2006; Haigh et al., 2016), but no differences in detecting light pressure on the skin (Cascio et al., 2008). Olfactory testing has shown that odor detection thresholds are not impacted in autistic children but that odor identification may be impaired (Sweigert et al., 2020; Bennetto et al., 2007) and related to increased ASD severity (Bennetto et al., 2007; Lane et al., 2010; May et al., 2011).

A growing body of literature supports the theory that sensory, social, and emotional systems in ASD may be impacted by an inhibition/excitation (I/E) imbalance (Rubenstein and Merzenich, 2003), specifically between glutamate (Glu) and gamma amino butyric acid (GABA). Research over the past decades has provided compelling evidence that differences in both GABA and Glu systems are present in autism. GABA, the most abundant inhibitory neurotransmitter, appears early in development and is critical for synapse and network formation. Genetic variations at loci encoding for GABA receptor subtypes have been widely reported (Buxbaum et al., 2002; McCauley et al., 2004) and reduction of GABA receptor proteins and binding (Mendez et al., 2013; Blatt et al., 2001; Fatemi et al., 2011) lower GABA concentration in the supplementary motor area (SMA) (Umesawa et al., 2020) sensory hyperactivity with GABAergic interneuron dysfunction (Chen et al., 2020), and associations of GABA/Glu ratio with neuroinflammation, ASD symptoms, and functional connectivity (El-Ansary and Al-Ayadhi, 2014; Zhang et al., 2020; Hegarty et al., 2018) demonstrate functional differences. Evidence for alterations in the Glutamatergic system include atypical levels of glutamate receptors and associated functions (Fatemi et al., 2011; Fatemi et al., 2018; Purcell et al., 2001) elevated glutamate concentrations in amygdala-hippocampal and parietal regions (Page et al., 2006), Glu modulation differences (Trobiani et al., 2018), and abnormalities in enzymes responsible for converting Glu to GABA (Yip et al., 2007; Yip et al., 2008).

This study measured regional brain GABA+, Glu, and GABA+/Glu ratios in autistic children, compared to groups of age and sex-matched children having sensory abnormalities (SA) or neurotypical development (TYP). In addition, we tested whether odor detection, odor identification, and social impairment were related to an imbalance of inhibitory/excitatory brain circuitry in 1) the amygdala-hippocampal region, a neural hub for both socioemotional and primary olfactory processing (Soudry et al., 2011) that is altered in ASD and, 2) in the cerebellum, which supports a range of social behaviors (Stoodley and Tsai, 2021) develops atypically in ASD (Fetit et al., 2021; Fatemi et al., 2012) and has been implicated in altered sensory processing timing in subgroups of ASD children (Welsh et al., 2023).