Introduction

Sensory overresponsivity (SOR) is a condition in which severe negative responses are experienced by an individual in response to triggering stimuli (Green et.al., 2018). Triggering stimuli may include auditory, visual, and tactile sensations along with any combination of the three. Common experienced stimuli, such as scratchy fabrics, loud noises, flashing lights, etc.  can elicit distress in individuals experiencing SOR while individuals without SOR have the privilege to be unbothered. While individuals experiencing SOR are heavily impacted in day-to-day life, little is understood about the mechanisms causing SOR, thus limiting treatment options.

Current theories characterize SOR as sensory responses that are faster, longer, or more intense than typical sensory responsivity (Lane, 2010). SOR is experienced by up to 15% of the general population and in over 50% of neurodivergent individuals (Wood et al., 2021). Neurodivergence is often used in the context of Autism spectrum disorders (ASD), but also refers to other neurological and developmental disorders like Attention Deficit/Hyperactivity Disorder (ADHD) or Obsessive Compulsive Disorder (OCD) (Baumer & Frueh, 2021).

Current research examined in this review is aimed towards understanding the mechanisms of SOR; current hypotheses suggest heightened sensory responses and/or dysregulations in emotional reactions to stimuli may be responsible for SOR symptoms experienced. fMRI and MRI scans along with MRI Diffusion Tensor Imaging (DTI), magnetic resonance spectroscopy, and psychological direct assessments appear to be the standard for investigative SOR research. Through these techniques, decreased habituation in the amygdala, over activation of the orbitofrontal cortex (OFC), and medial prefrontal cortical (mPFC) and thalamocortical (TC) connectivity/neurochemical transmission are implicated as possible mechanisms of SOR, while altered GABA/glutamate concentrations in the thalamus have been suggested as possible markers of SOR. Understanding the mechanisms behind SOR may not only lead to the mitigation of environmental and social distresses experienced by those with SOR but may also be a useful diagnostic marker for ASD and lead to more accurate diagnoses and improved qualities of life.

The Main Players: Brain area connectivity implicated in SOR

The thalamus is a major relay center in the brain that conveys sensory and motor signals and plays a part in regulation of awareness and consciousness (Torrico & Sunil Munakomi, 2021). Because of the large role the thalamus has in sensory processing, the thalamus is a major target of sensory processing dysfunction research in SOR. Recent research conducted at Johns Hopkins University School of Medicine used magnetic resonance spectroscopy to measure GABA and glutamate levels in the thalamus and the primary sensorimotor cortex. Higher levels of glutamate were found to be associated with reduced inhibition during tactile sensory perception (He et. al., 2021). This research not only implicates the thalamus as having a role in SOR but offers evidence that SOR dysfunction could be occurring during the sensory processing pathway via lack of appropriate inhibition.

The amygdala, a major emotional regulating center, has also been a target of SOR research; particularly in understanding if dysfunction occurs in the emotional response to stimuli. Deficits in amygdala habituation to stimuli have been observed in ASD individuals with SOR as well as hyperactivity in the amygdala (Green et al., 2015). This research suggests that SOR may impact top-down emotional regulation causing a behavioral dysregulation in response to stimuli. Because amygdala function is likely to be altered in SOR individuals, inputs and outputs to and from the amygdala must also be understood to determine SOR mechanisms.

The orbito-frontal cortex (OFC) is another structure implicated as a potential player in sensory dysfunction via its important influence on top-down emotion downregulation (Green et al., 2015). The OFC receives input from visual, gustatory, olfactory, somatosensory, and auditory cortices and projects to the mPFC, amygdala, cingulate cortex, striatum, and hypothalamus among others (Rolls et al., 2020). Because of the OFC’s involvement in sensory processing, research has examined how functional connectivity between the amygdala and OFC is influenced in SOR (Green et al., 2015).

In healthy control brains, OFC and amygdala activity represent a negative feedback loop: OFC activation inversely relates to amygdala activation and increased OFC activation is associated with decreased amygdala activation in response to certain stimuli (Green et al., 2015). Research comparing neurotypical youth with ASD youth experiencing SOR found overactivation in the OFC as well as the limbic area in response to mildly aversive sensory stimuli (Green et al., 2015). Failure of the OFC to downregulate amygdala activation may explain the overactivation in the limbic system and the OFC in ASD youth. Similar dysfunction in OFC and amygdala connectivity is also observed in subjects presenting with social anxiety disorder, which has a high comorbidity with ASD (approximately 50%) (Maddox & White, 2015). Social anxiety disorder is marked by an over-reactivity of fear-related circuits which can also be seen in many SOR individuals via the severe negative behavioral reaction to sensory stimuli. Studies have shown that positive connectivity between the OFC and amygdala, indicative of an excitatory connection, also occurs in social anxiety disorder (Sladky et al., 2013). Further examination of the OFC and amygdala connectivity in relation to SOR may offer a basis of treatment options for SOR as well as diagnostic abilities.

The medial prefrontal cortex (mPFC) is fundamental to social interaction and cognition (Martínez-Sanchis, 2014). The mPFC has integrative roles involving memory and emotional processing, higher-order sensory integration, and top-down behavioral processing via its reciprocal connections with the amygdala, hippocampus, and temporal cortex (Martínez-Sanchis, 2014). The role of the mPFC has recently been examined in context of sensory processing and is thought to play a role in anxiety regulation and downregulation of negative emotional affects (Skirzewski et al., 2022). Decreased habituation to sensory stimuli can result in a heightened perception of threat leading to increased anxiety responses, making the mPFC a target for anxiety treatments in SOR individuals (South & Rodgers, 2017).  

Optogenetic activation of basolateral amygdala projections (BAP) to the mPFC were shown to increase anxiety-related behaviors in mice while inhibition of the basolateral amygdala inputs decreased anxiety behaviors (Skirzewski et. al., 2022). The negative behavioral response to stimuli observed in SOR may result from increased inputs of the BAP to the mPFC but human research is needed. Current human studies show that increasing and maintaining mPFC activation in ASD youth, via increased behavioral direction to important social cues, is associated with lower levels of sensory over-responsivity and, as a result, lower levels of social difficulties (Patterson et al., 2021). While research has yet to reach a relative consensus on what role the mPFC plays in SOR, manipulation of mPFC activity via attention direction does influence social capabilities and SOR severity suggesting that behavioral modification may offer a possible method to mitigate SOR difficulties. This research also prompts further investigation into the mPFC and its sensory integration and emotional processing roles as deviations from neurotypical mPFC activation is consistently shown in SOR research.

Understanding how the thalamus, amygdala, mPFC, and OFC all connect can yield a larger picture of sensory processing and resulting emotional responses. Once the larger picture is understood, mechanisms of SOR may be localized.

Implications of this Research: Behavioral versus Sensory Dysfunction

Because sensory input and emotional processing are heavily interconnected, determining whether sensory processing or behavioral processing dysfunctions are responsible for SOR is difficult. As mentioned above, irregularities in GABA/glutamate concentrations in thalamocortical circuits were correlated with SOR severity and GABA concentration was a predictor of altered thalamocortical connectivity (Wood et al., 2021). Because thalamocortical connectivity is a major route of sensory input/processing, the emerging theory that sensory processing dysfunction may be a primary mechanism of SOR can be supported. Research using SOR mouse models also show that deletion of the Fmr1 gene (a gene responsible for making FMRP protein contributing to Fragile X syndrome) in VGlut2- expressing glutamatergic neurons present in subcortical brain regions (like the thalamus) can eliminate symptoms of SOR (Gonzalez et al., 2019). This research also implicates sensory processing dysfunction as the more likely mechanism behind SOR. Other research, however, suggests emotional processing dysfunction as the mechanism of SOR via amygdala dysfunction observed via fMRI (Green et al., 2019).  Overall, both sensory and behavioral processing dysfunctions are likely to be contributing to SOR symptoms but much more research is needed to determine and localize SOR mechanisms.

Future Directions:

Much of SOR research utilizes fMRI and ASD behavioral tests to understand how brain activation is altered in SOR individuals. Through this research, behavioral therapies that may mitigate symptoms for those experiencing SOR could be possible. While SOR social impairment effects are still under-researched, attention modulation was found to restore social cognitive deficits caused by sensory stimuli in SOR individuals (Green et al., 2018). This research provides not only a rationale for continued research, but also a basis for the development of behavioral therapies for SOR individuals.

A promising route to the determination of diagnostic markers and prospective treatment options may be through research examining OFC and amygdala connectivity. Multiple experimentations regarding the OFC and amygdala connection in SOR, ASD, and other disorders have all yielded identical results. OFC and amygdala connectivity efficacy has been shown to exhibit dysfunction in response to facial emotion discrimination tasks in a variety of experimental paradigms (Sladky et al., 2013) (Green et al., 2015). Because OFC and amygdala connectivity has been implicated in SOR and multiple behavioral disorders, experimentation beyond fMRI observation of activity of the circuit is warranted. Neurophysiological and neurochemical experimentation in SOR mouse models could aid in identifying how the altered connectivity is occurring which could lead to diagnostic markers for SOR and many other disorders like ASD and social anxiety disorder.

When considering future directions in SOR research it is vital to note that in all the literature previously cited, only male subjects were used. Research examining functional connectivity in the salience network (a network critical for detecting behaviorally pertinent stimuli and coordinating neurological responses to said stimuli) in male and female subjects found significant sex differences in salience network connectivity between ASD subjects (Cummings et al., 2020). This is not the only study demonstrating profound discrepancies between the sexes in SOR individuals. Because such differences exist, it is crucial that future research include both male and female participants if any future SOR diagnostic markers and/or treatments are to be proposed.

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[+] Other Work By Chandler Fanning