The functional neuroanatomy of auditory sensory gating and its behavioural implications

Auditory sensory gating (ASG) is the ability in individuals to suppress incoming irrelevant sensory input, indexed by evoked response to paired auditory stimuli. ASG is impaired in psychopathology such as schizophrenia, in which it has been proposed as putative endophenotype. This study aims to characterise electrophysiological properties of the phenomenon using MEG in time and frequency domains as well as to localise putative networks involved in the process at both sensor and source level. We also investigated the relationship between ASG measures and personality profiles in healthy participants in the light of its candidate endophenotype role in psychiatric disorders. Auditory evoked magnetic fields were recorded in twenty seven healthy participants by P50 ‘paired-click’ paradigm presented in pairs (conditioning stimulus S1- testing stimulus S2) at 80dB, separated by 250msec with inter trial interval of 7-10 seconds. Gating ratio in healthy adults ranged from 0.5 to 0.8 suggesting dimensional nature of P50 ASG. The brain regions active during this process were bilateral superior temporal gyrus (STG) and bilateral inferior frontal gyrus (IFG); activation was significantly stronger in IFG during S2 as compared to S1 (at p<0.05). Measures of effective connectivity between these regions using DCM modelling revealed the role of frontal cortex in modulating ASG as suggested by intracranial studies, indicating major role of inhibitory interneuron connections. Findings from this study identified a unique event-related oscillatory pattern for P50 ASG with alpha (STG)-beta (IFG) desynchronization and increase in cortical oscillatory gamma power (IFG) during S2 condition as compared to S1. These findings show that the main generator for P50 response is within temporal lobe and that inhibitory interneurons and gamma oscillations in the frontal cortex contributes substantially towards sensory gating. Our findings also show that ASG is a predictor of personality profiles (introvert vs extrovert dimension)

Large-Scale Networks for Auditory Sensory Gating in the Awake Mouse

The amplitude of the brain response to a repeated auditory stimulus is diminished as compared to the response to the first tone (T1) for interstimulus intervals (ISI) lasting up to hundreds of milliseconds. This adaptation process, called auditory sensory gating (ASG), is altered in various psychiatric diseases including schizophrenia and is classically studied by focusing on early evoked cortical responses to the second tone (T2) using 500-ms ISI. However, mechanisms underlying ASG are still not well-understood. We investigated ASG in awake mice from the brainstem to cortex at variable ISIs (125-2000 ms) using high-density EEG and intracerebral recordings. While ASG decreases at longer ISIs, it is still present at durations (500-2000 ms) far beyond the time during which brain responses to T1 could still be detected. T1 induces a sequence of specific stable scalp EEG topographies that correspond to the successive activation of distinct neural networks lasting about 350 ms. These brain states remain unaltered if T2 is presented during this period, although T2 is processed by the brain, suggesting that ongoing networks of brain activity are active for longer than early evoked-potentials and are not overwritten by an upcoming new stimulus. Intracerebral recordings demonstrate that ASG is already present at the level of ventral cochlear nucleus (vCN) and inferior colliculus and is amplified across the hierarchy in bottom-up direction. This study uncovers the extended stability of sensory-evoked brain states and long duration of ASG, and sheds light on generators of ASG and possible interactions between bottom-up and top-down mechanisms

The Effects of Anxiety on Sensory Gating

Sensory gating is a proposed important physiological process of inhibiting neuronal responses of repetitious stimuli in the central nervous system to allocate more cognitive resources to additional salient information. Sensory gating is currently being studied to better understand psychiatric illnesses, especially those characterized by emotional changes and the inability to concentrate such as schizophrenia, ADHD, anxiety disorder, and Parkinson’s. Anxiety is a strong feeling of nervousness that occurs in all individuals at varying degrees and is associated with detrimental health effects as well as hindering concentration. Numerous brain regions are associated with anxiety levels such as the anterior limbic system, paralimbic system, hippocamus, and prefrontal cortex. These systems have also activity related to sensory gating. Data was obtained from 10 Caucasian, undergraduate females. We used a set of inventories to determine participants\u27 level of anxiety as well as measuring their auditory gating through the click-pair paradigm, with 500ms between clicks and 10 seconds between pairs of clicks. We hypothesize that increasing levels of anxiety will be correlated with impaired gating, indicated by increased ratios. To determine this, participants engaged in the cold-pressor task to induce stress. Baselines were established before the cold-pressor tasks and measured after its completion. Stress levels were shown to increase after the application of the cold-pressor task, but gating ratios were demonstrated to be unaltered. Future studies are proposed further explore the relationship between anxiety and sensory gating

Topological Biomarker of Alzheimer’s Disease

For years, it has been assumed that the cerebral accumulation of pathologic protein forms is the main trigger of Alzheimer’s disease (AD) pathology; however, recent studies revealed strong evidences that the alternations in synaptic activity precede and affect the homeostasis of amyloid-beta and tau, both of which aggregate during AD. Given that the neuropathological changes, characteristic for AD, start decades before the onset of the first symptoms, when alternations become irreversible, it is crucial to find a biomarker that can detect the preclinical signs of disease, presumably synaptic dysfunction of specific cerebral areas. Here is presented a novel, a high potential neuroimaging biomarker that can detect the postsynaptic dysfunction of specific neural substrate located in medial prefrontal cortex (mPFC) during sensory gating processing of a simple auditory stimulus. The magnetoencephalography-based localization of mPFC gating activation has the potential not only to detect symptomatic AD but also to become a predictor of cognitive decline related to the pathophysiological processes of AD, both at the individual level. The strengths of proposed biomarker lie in the simplicity of using a binary value, i.e., activated or not activated a neural generator along with its potential to follow the evolution of the pathophysiological process of disease from preclinical phase. The novel biomarker does not require estimation of uniform cutoff levels and standardization processes, the main problems of so far proposed biomarkers. Ability to individually detect AD pathology during putative preclinical and clinical stages, absolute noninvasiveness, and large effect size give this biomarker a high translation capacity and clinical potential

Cognitive mechanisms associated with auditory sensory gating

Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants additionally completed a paired-stimulus paradigm as a measure of auditory sensory gating. A correlational analysis revealed that several tasks correlated significantly with sensory gating. However once fluid intelligence and working memory were accounted for, only a measure of latent inhibition and accuracy scores on the continuous performance task showed significant sensitivity to sensory gating. We conclude that sensory gating reflects the identification of goal-irrelevant information at the encoding (input) stage and the subsequent ability to selectively attend to goal-relevant information based on that previous identification

A Review of the Role of Auditory Evoked Potentials in Mild Traumatic Brain Injury Assessment

Around 75% to 90% of people who experience a traumatic brain injury (TBI) are classified as having a mild TBI (mTBI). The term mTBI is synonymous with concussion or mild head injury (MHI) and is characterized by symptoms of headache, nausea, dizziness, and blurred vision. Problems in cognitive abilities such as deficits in memory, processing speed, executive functioning, and attention are also considered symptoms of mTBI. Since these symptoms are subtle in nature and may not appear immediately following the injury, mTBI is often undetected on conventional neuropsychological tests. Current neuroimaging techniques may not be sensitive enough in identifying the array of microscopic neuroanatomical and subtle neurophysiological changes following mTBI. To this end, electrophysiological tests, such as auditory evoked potentials (AEPs), can be used as sensitive tools in tracking physiological changes underlying physical and cognitive symptoms associated with mTBI. The purpose of this review article is to examine the body of literature describing the application of AEPs in the assessment of mTBI and to explore various parameters of AEPs which may hold diagnostic value in predicting positive rehabilitative outcomes for people with mTBI

Event-related potential studies of somatosensory detection and discrimination.

This thesis contains four studies, the first examining methodology issues and four subsequent ones examining somatosensory cortical processing using event-related potentials (ERPs). The methodology section consists of 2 experiments. The first compared the latency variability in stimulus presentation between 3 computers. The second monitored the applied force of the vibration stimuli under experimental conditions to ensure that the chosen method for somatosensory stimulus presentation was consistent and reliable. The next study involved 3 experiments that aimed to characterize the mid to long latency somatosensory event-related potentials to different duration vibratory stimuli using both intracranial and scalp recording. The results revealed differences in the waveform morphology of the responses to and on-off responses, which had not previously been noted in the somatosensory system. The third and fourth studies each consisted of 2 experiments. These examined the discrimination between vibratory stimuli using an odd-ball paradigm to try to obtain a possible 'mismatch' response, similar to that reported in the auditory system. The aim of this study was to clarify some of the discrepancies in the literature surrounding the somatosensory mismatch response and to further characterize this response. The results from intracranial and scalp ERP recordings showed a two-component, negative-positive mismatch response over the anterior parietal region and a negative component over the superior pre-frontal region in response to changes in both frequency and duration. The negative component over the frontal region had never before been described. The last study explored possible interactions between somatosensory and auditory cortical potentials in response to spatially and temporally synchronized auditory and vibratory stimuli. The results showed clear interactions in the cortical responses to combined auditory and somatosensory stimuli in both standard and mismatch conditions

Auditory Brainstem Response with Cognitive Interference in Normal and Autism Spectrum Disorder Children - Understanding the Auditory Sensory Gating Mechanism

Earlier studies disputed the influence of higher-order function such as attention or cognitive inhibition on the auditory brainstem response (ABR) result. In short, the ABR result was considered similar with or without the subject paying attention. However, in the last few years, there has been growing evidence that the higher-order function may influence the ABR findings provided the sensory gating system of the brain is triggered by any cognitive interference activities. This chapter will explain the concept of auditory sensory gating, a method to measure auditory sensory gating, and at the end of the chapter, preliminary findings concerning the ABR with cognitive interference among ten normally developing children are presented. This chapter will also share a case study that compared auditory sensory gating capacity in normal and children with mild autism spectrum disorder (ASD)

Neurophysiology in psychosis: The quest for disease biomarkers

Psychotic disorders affect 3% of the population at some stage in life, are a leading cause of disability, and impose a great economic burden on society. Major breakthroughs in the genetics of psychosis have not yet been matched by an understanding of its neurobiology. Biomarkers of perception and cognition obtained through non-invasive neurophysiological tools, especially EEG, offer a unique opportunity to gain mechanistic insights. Techniques for measuring neurophysiological markers are inexpensive and ubiquitous, thus having the potential as an accessible tool for patient stratification towards early treatments leading to better outcomes. In this paper, we review the literature on neurophysiological markers for psychosis and their relevant disease mechanisms, mainly covering event-related potentials including P50/N100 sensory gating, mismatch negativity, and the N100 and P300 waveforms. While several neurophysiological deficits are well established in patients with psychosis, more research is needed to study neurophysiological markers in their unaffected relatives and individuals at clinical high risk. We need to harness EEG to investigate markers of disease risk as key steps to elucidate the aetiology of psychosis and facilitate earlier detection and treatment