Neurometric Profiling of Autism Spectrum Disorder using The Brief Neurometric Battery: A Novel Eeg Based Task

Autism spectrum disorder is a pervasive developmental disorder characterized by heterogeneous deficits in social communication and interaction, as well as repetitive behaviors and restricted interests. Due to the dramatic increase in prevalence, a major theme in contemporary research has been the identification of biomarkers for ASD that can shed light on etiological factors, facilitate diagnosis and serve as markers for tracking the efficacy of behavioral and pharmacological treatments. Electroencephalography (EEG) metrics, such as event-related potentials (ERPs), resting state oscillatory activity (OA), and resting state complexity (multiscale entropy), are well-suited for the measurement of such biomarkers. Due to the complexity and heterogeneity of ASD symptoms, it is important that research aiming to use EEG to identify biomarkers of autism and other neurodevelopmental disorders focus on determining the relationships between electrophysiological neurometrics and clinical presentation. The objective of the present research was two-fold; 1) synthesize a profile of ERP and OA metrics, collected during a novel Brief Neurometric Battery, that differentiates between youth with ASD and controls, and 2) determine if a relatively novel analysis of resting state EEG complexity (MSE) can be used to differentiate between ASD and controls. Through a two study approach, this research was able to synthesize a multivariate profile that classified youth with and without ASD at an accuracy rate comparable to that of the gold standard methods (ADI-R/ADOS) and identify an additional neurometric, multiscale entropy, that can accurately differentiate between youth with ASD and controls

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

Hormonal Correlates of P50 Suppression in Socially Anxious Young Adults

Ten to 15% of the population is temperamentally shy and have elevated physiological stress responses to novel social situations. Yet, the neural mechanisms underlying this personality trait are not fully understood (Beaton et al., 2009; Schmidt et al., 1997). Efficiently attending to, acting on, and remembering relevant stimuli and filtering out less important information is critical given the sheer volume of sensory and perceptual stimuli the brain is exposed to. Relevant stimuli that garner attention are remembered and consolidated with existing memories. Stimuli that do not warrant extended attention are ignored or habituated to in a process underpinned by cortical and subcortical inhibitory brain networks that reduce processing load on finite attentional resources (Freedman et al., 1991; Adler et al., 1998). Inefficient filtering of irrelevant stimuli could underpin anxiety in those with temperamental shyness and anxiety (Aron, Aron, & Davies, 2005). We measured the P50 auditory event-related potential (ERP) using a paired auditory click paradigm, as well as self-reported social anxiety and shyness, and salivary cortisol in two groups of healthy young adults selected for being very shy or very gregarious. While shy and gregarious groups demonstrated a similar P50 ERP to sound one (S1), the shy group showed elevated P50 amplitudes in response to the second sound (S2) compared to the gregarious group. Participants categorized as being lower or higher on social anxiety displayed a reverse pattern: those higher in social anxiety had a reduced response to S1 compared to those lower in social anxiety, yet a similar response to S2. Further, higher salivary cortisol predicted smaller differences and larger ratios in the P50 ERP from S1 to S2

Mild Traumatic Brain Injuries and Their Implications on Changes in Event Related Potentials: A look into Visual Gating (P50)

Concussions are a prevalent injury that affect a wide range of individuals. Commonly seen amongst individuals who play contact sports, there are many underlying factors that doctors and clinicians have yet to understand which include properties such as proper diagnosis standards or lasting impacts. In this study, we look at those impacts by using electroencephalographic (EEG) measures to study the changes in event related potentials (ERPs) associated with sensory gating and how this cognitive property is affected in those who have a self-reported concussion. Here we show that a visual attention and gating mechanism exists in both populations (control and concussed) as seen by the P50 ERP after the presentation of our visual stimulus, which is dependent on the Order the stimulus is presented (1st or 2nd). Our findings show that those who have suffered a concussion show a difference in the ability to sensory gate which is prevalent by the differences in ERPs between the two groups

Abnormal Beta and Gamma Frequency Neural Oscillations Mediate Auditory Gating in Schizophrenia

Sensory gating is a process in which the brain’s response to irrelevant and repetitive stimuli is inhibited. Poor P50 gating in those with schizophrenia is typically measured by the ratio or difference score of the event-related potential (ERP) amplitudes in response to a paired click paradigm. Failure to suppress the ERP in response to the second click is thought to reflect a faulty inhibitory system. Oscillatory activity during the inter-click interval in the beta (20-30 Hz) and gamma (30-50 Hz) frequency bands may reflect inhibitory processes initiated by the first click. Paired-auditory stimuli were presented to 131 participants with schizophrenia and 196 healthy controls. P50 ERP amplitude as well as averaged- and single-trial beta (20-30 Hz) and gamma (30-50 Hz) frequency power during the inter-click interval were measured from the CZ electrode site. Data were analyzed using a series of ANOVAs and regression models. The statistical analyses provide evidence that patients with schizophrenia exhibited less evoked beta and gamma power across the delay interval, particularly at the 0-100 ms time point, in response to S1. We found that evoked beta and gamma responses early during the 500 ms delay interval (0-100 ms) are critical in determining the S1 amplitude and extent of P50 gating across the delay interval for both healthy controls and individuals with schizophrenia. Our findings also support a disruption in “gating in” processes in those with schizophrenia. The investigation of oscillatory activity at different time points during the inter-click interval may provide a new framework for studying the mechanisms that support sensory inhibition, and may help researchers and clinicians develop future cognitive training protocols

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)

Tinnitus and Decreased Subcortical and Cortical Inhibition

Background: The perception of tinnitus may be triggered by a reduction in inhibitory function in the central auditory nervous system. Evidence, primarily from invasive studies of animal models of tinnitus, indicates that these changes occur at both the subcortical and cortical level. Auditory evoked potential (AEP) indices of subcortical inhibition [auditory brainstem response (ABR) 〖 V/I 〗_ amp ratio ] and cortical inhibition [cortical auditory evoked potential (CAEP) sensory gating ratios] may provide an objective index of whether reduced subcortical and/or cortical inhibition is associated with tinnitus perception in humans. The aims of this study were to assess whether ABR and/or CAEP indices of subcortical and cortical inhibition distinguish between a group with constant tinnitus and matched non-tinnitus controls, and whether tinnitus presence and/or other factors [age, noise exposure history, hearing loss, speech perception in noise (SPIN)] predicted ABR and/or CAEP outcomes related to inhibition. Methods: Individuals with tinnitus and control counterparts matched for sex, age, and hearing thresholds completed the study (n = 18 per group). ABRs were recorded with a tiptrode in response to high intensity click ABRs to determine the 〖 V/I 〗_ amp ratio . CAEPs were recorded in response to two successive high intensity 10 ms clicks. A ratio of the amplitude or area of the first (conditioning CAEP) and second (test CAEP) click response was determined ( test CAEP / conditioning CAEP ) as the primary measure of sensory gating. The latency ratio was also determined as a secondary outcome which may relate to sensory gating. For both the ABR 〖 V/I 〗_ amp ratio and CAEP sensory gating ratios, a larger value indicated reduced inhibition. Ratios were compared between the two groups using independent t-tests. The relative predictive value (proportional reduction in error, PRE) of tinnitus, age, noise exposure history, hearing loss, and SPIN on ABR and CAEP outcome variables related to inhibition was analyzed using regression. Results: Individuals with tinnitus, relative to controls, exhibited similar ABR 〖 V/I 〗_ amp ratio , and significantly larger sensory gating 〖 P1 〗_ lat ratio . None of the variables assessed significantly predicted the ABR 〖 V/I 〗_ amp ratio . Tinnitus significantly predicted 〖 P1-N1 〗_ amp ratio , but not when taking into account age, noise exposure history, hearing loss, and SPIN. The 〖 P1 〗_ lat ratio was significantly predicted by both tinnitus and age, however, best predicted by age. Conclusions: Tinnitus-related reduced inhibition was not evident at the subcortical level based on the ABR 〖 V/I 〗_ amp ratio . At the cortical level, the predictive influence of tinnitus on the 〖 P1-N1 〗_ amp ratio supports the association between reduced sensory gating with tinnitus presence in humans. The significantly larger 〖 P1 〗_ lat ratio in the tinnitus group may also support reduced sensory gating and/or a change in the recovery time, or refractoriness, of auditory evoked responses in individuals with tinnitus. The strong predictive influence of age on the 〖 P1 〗_ lat ratio indicates that increasing age reduced sensory gating above and beyond the effects of tinnitus. Potential limitations to the current study, including the non-normally distributed participant characteristics and AEP methodologies, as well as considerations for future research aiming to improve the reliability and validity of tinnitus AEP assessments are discussed

Differential effects of cannabis use on event-related potential (ERP)-indexes of cortical inhibition in cannabis users and non-users

Cannabis has psychoactive properties and is thought to be associated with potential structural and functional changes with early and heavy use. Previous research suggests cannabis users (CU) vs. non-users (NU) have deficits on EEG-derived event-related potentials elicited by paired click and visual Go/NoGo paradigms. We used these paradigms to examine inhibitory functioning in CUs (n = 14; 9 male) vs. NUs (n = 16, 4 male). Effect sizes suggest CUs had impaired N100 measures of sensory gating compared to NUs. Additionally, a trend level interaction and latency findings for the P200 suggested CUs had smaller amplitudes and quicker latencies to S1 compared to NUs. Go/NoGo findings revealed enhanced P100 amplitudes in CUs (vs. NUs). No other between-group differences or sex differences were observed. This study provides further support for cannabis-induced deficits on early-attentional processing as indexed by the N100 and novel findings regarding enhanced P100 amplitudes to the Go/NoGo paradigm