Sensory Over Responsivity: Key Insights on GABA’s Role

Some individuals experience heightened sensitivity to sensory input, reacting intensely to sounds, textures, lights, or other stimuli. This phenomenon, known as sensory over-responsivity (SOR), can significantly impact daily life, contributing to discomfort and challenges in social or environmental interactions.

Research suggests that the neurotransmitter gamma-aminobutyric acid (GABA) plays a critical role in regulating sensory responses. Understanding its involvement may explain why some people are more sensitive to sensory input than others.

Neural Mechanisms In Sensory Processing

The brain continuously filters and interprets sensory information, prioritizing relevant stimuli while suppressing extraneous input. This balance between excitatory and inhibitory neural activity relies on GABA, which fine-tunes neural circuits by dampening excessive excitatory signaling, preventing sensory overload, and maintaining perceptual stability. Disruptions in this balance can lead to heightened sensitivity, as seen in individuals with SOR.

Sensory processing begins at peripheral receptors, where specialized neurons detect stimuli such as sound waves, light, or tactile pressure. These signals travel via afferent pathways to primary sensory cortices for initial processing. In the auditory system, cochlear hair cells convert mechanical vibrations into electrical signals that reach the auditory cortex. Similarly, mechanoreceptors in the skin relay touch-related information to the somatosensory cortex. At each stage, inhibitory interneurons regulate signal strength to ensure only the most relevant inputs reach higher-order processing centers.

Within the cerebral cortex, sensory integration occurs through networks of excitatory pyramidal neurons and inhibitory interneurons, particularly those expressing GABA. Parvalbumin-positive (PV+) interneurons, a subtype of GABAergic cells, are crucial for shaping sensory perception by generating fast-spiking inhibitory responses that synchronize neural oscillations. Studies using optogenetics and electrophysiology have shown that reduced PV+ interneuron activity leads to increased cortical excitability, heightening sensitivity to sensory stimuli. This mechanism has been implicated in conditions such as autism spectrum disorder (ASD), where altered GABAergic signaling is linked to atypical sensory experiences.

Thalamocortical circuits also play a fundamental role in sensory gating, filtering out redundant or irrelevant stimuli. The thalamus acts as a relay station, transmitting sensory information to the cortex while receiving inhibitory feedback to regulate signal flow. GABAergic neurons within the thalamic reticular nucleus (TRN) refine sensory input before it reaches conscious awareness. Functional imaging studies show that individuals with sensory hypersensitivity often exhibit reduced TRN inhibition, allowing excessive sensory information to reach the cortex, making everyday experiences overwhelming.

GABAergic Signaling And Sensory Over Responsivity

GABA plays a central role in regulating sensory processing, ensuring a balance between excitation and inhibition. In individuals with SOR, disruptions in GABAergic signaling can lead to an exaggerated response to sensory input. This dysregulation may stem from altered GABA synthesis, receptor function, or interneuron activity, affecting how sensory signals are modulated in the brain.

Magnetic resonance spectroscopy (MRS) studies indicate that individuals with SOR often have lower GABA concentrations in sensory-related brain regions, such as the somatosensory and auditory cortices. A 2013 study published in NeuroImage found that children with ASD and heightened sensory sensitivity had reduced GABA levels in primary sensory cortices compared to neurotypical controls. This deficiency suggests compromised inhibitory control over excitatory neurons, leading to an increased perception of sensory stimuli. Electrophysiological recordings further support this idea, showing that reduced GABAergic inhibition correlates with prolonged neural responses to sensory input, amplifying the perception of touch, sound, or light.

GABA receptor function also plays a role in sensory gating. The two primary types of GABA receptors—GABA_A and GABA_B—mediate fast and slow inhibitory signaling, respectively. Dysfunction in these receptors can impair sensory filtering, contributing to hypersensitivity. Pharmacological studies show that drugs enhancing GABAergic transmission, such as benzodiazepines that modulate GABA_A receptors, can reduce sensory hyperreactivity. Conversely, genetic mutations affecting GABA receptor subunits have been linked to sensory processing abnormalities, reinforcing the importance of receptor integrity in maintaining sensory equilibrium.

Interneuron dysfunction, particularly in circuits involving PV+ interneurons, further complicates the picture. These fast-spiking inhibitory neurons synchronize cortical activity and refine sensory perception. Reduced PV+ interneuron function has been observed in neurodevelopmental disorders associated with SOR, such as ASD and fragile X syndrome. Animal models with impaired PV+ interneuron activity exhibit heightened responses to tactile and auditory stimuli, mirroring the sensory challenges seen in affected individuals. This suggests that interventions aimed at restoring PV+ interneuron function could help manage sensory hypersensitivity.

Sensory Modality Profiles

Individuals with SOR do not experience heightened sensitivity uniformly across all sensory domains. Instead, distinct modality profiles emerge, with some reacting intensely to tactile input while others are more sensitive to auditory, visual, or olfactory stimuli. These variations suggest that different sensory systems may be differentially affected by underlying neural mechanisms, shaping an individual’s perceptual experience.

Tactile over-responsivity is one of the most commonly reported sensory challenges, often presenting as an aversion to certain textures, fabrics, or even light touch. Research shows that individuals with heightened tactile sensitivity exhibit exaggerated cortical responses in the somatosensory system, particularly in the primary somatosensory cortex (S1). Functional MRI studies demonstrate that those with tactile hypersensitivity show increased activation in S1 when exposed to stimuli that neurotypical individuals perceive as neutral. This heightened response can interfere with daily activities, making clothing choices, grooming, or physical contact sources of discomfort.

Auditory over-responsivity manifests as an exaggerated reaction to sounds that others may find benign, such as background chatter, household appliances, or sudden noises. Electroencephalography (EEG) studies reveal that individuals with auditory hypersensitivity exhibit prolonged auditory evoked potentials, indicating difficulty dampening sound processing. This prolonged neural response can lead to distress in environments with unpredictable noise levels, such as crowded public spaces or classrooms.

Visual hypersensitivity is another modality in which individuals with SOR struggle to filter excessive visual input. Bright lights, rapid motion, or high-contrast patterns can cause discomfort. Research suggests heightened activity in the occipital cortex, responsible for processing visual information, contributes to this sensitivity. This can make settings with fluorescent lighting or fast-moving visual stimuli, such as busy streets or digital screens, particularly challenging.

Patterns In Brain Imaging Studies

Neuroimaging research has provided valuable insights into the neural mechanisms underlying SOR, revealing distinct patterns of altered brain activity and connectivity. Functional magnetic resonance imaging (fMRI) studies indicate that individuals with SOR exhibit hyperactivation in sensory processing regions, particularly the primary and secondary sensory cortices. This heightened activity suggests that sensory stimuli are processed with greater intensity, contributing to overwhelming perceptual experiences.

Structural imaging using diffusion tensor imaging (DTI) has identified differences in white matter integrity, particularly in pathways connecting sensory regions to higher-order cortical areas. These findings suggest disruptions in the efficient transmission of sensory information.

Resting-state functional connectivity analyses highlight atypical interactions between sensory cortices and regulatory brain regions such as the prefrontal cortex and anterior cingulate cortex. Individuals with SOR may have difficulty modulating sensory input, leading to exaggerated neural responses even in the absence of external stimuli. Studies using positron emission tomography (PET) have also indicated altered neurotransmitter dynamics, with some reports showing abnormal GABAergic activity in sensory-related brain regions, reinforcing the idea that inhibitory control mechanisms may be compromised.

Potential Genetic Influences

Genetic factors contribute to SOR, with research identifying specific genes associated with altered sensory processing. Variants in genes related to GABA signaling, such as GABRB3 and GAD1, have been implicated in atypical sensory responses. GABRB3, encoding a subunit of the GABA_A receptor, has been linked to neurodevelopmental conditions like ASD, where sensory hypersensitivity is common. Reduced expression of this gene may impair inhibitory signaling, disrupting the brain’s ability to regulate sensory input effectively. Similarly, GAD1 encodes glutamate decarboxylase, an enzyme responsible for GABA synthesis. Studies show that reduced GAD1 expression correlates with lower GABA levels in sensory-related brain regions, contributing to heightened neural excitability and increased sensitivity to stimuli.

Beyond GABA-related genes, other genetic pathways involved in neuronal excitability and synaptic regulation have been linked to SOR. Variants in SCN2A, a gene encoding a sodium channel subunit critical for neuronal firing, are associated with altered sensory thresholds. Individuals with SCN2A mutations often exhibit hypersensitivity to auditory and tactile stimuli, suggesting that disruptions in ion channel function contribute to sensory dysregulation. Additionally, polymorphisms in BDNF (brain-derived neurotrophic factor) influence synaptic plasticity and neuronal development, with altered expression linked to sensory hypersensitivity and broader neurodevelopmental conditions. These genetic findings highlight the complexity of SOR, suggesting multiple molecular pathways shape sensory experiences.