Anxiety and initial value dependence in startle habituation.

Studies suggest that deficits in startle reflex habituation occur in trait and clinical anxiety. Measures of habituation are affected by the magnitude of the initial response, with larger initial responses predicting a steeper decline in response over repeated trials. This relationship between initial value and change, commonly called the Law of Initial Value or initial value dependence (IVD), has been partialled out as a covariate in habituation research, but variation in IVD may be informative in itself, reflecting differences in physiological reactivity. The present study explored how trait anxiety and contextual anxiety relate to habituation kinetics of the startle eyeblink response: initial value, linear habituation slope, and the relationship between them (IVD). Participants (n = 31; 15 Control, 16 Contextual Anxiety [CA]) were exposed to two blocks of acoustic startle stimuli, and CA participants were warned that they may receive an electrical shock to the wrist during block 2. Trait anxiety did not predict habituation slope, but it did predict a weaker IVD relationship, meaning that high initial startle magnitude was less predictive of a steep response decline in trait-anxious subjects. Meanwhile, CA did not impact startle habituation or IVD. The results suggest that individual differences in trait anxiety are related to the relationship between initial physiological response magnitude and subsequent change in response. IVD in startle habituation may thus serve as a better biomarker of healthy emotional responding than startle habituation per se.

It is never as good the second time around: Brain areas involved in salience processing habituate during repeated drug cue exposure in treatment engaged abstinent methamphetamine and opioid users.

The brain response to drug-related cues is an important marker in addiction-medicine. However, the temporal dynamics of this response in repeated exposure to cues are not well known. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations all abstinent during their early recovery (treatment). Sixty-five male participants (35.8 ± 8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample from an abstinence-based residential treatment program. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD from a different residential program and 22 male with opioid use disorder from the same residential program as the discovery sample). The second replication sample was re-tested within two weeks. In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both a main effect of condition and a condition-by-time interaction, indicating a habituating response to drug-related but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed a consistent lack of drug > neutral and habituation response within all selected clusters in the second cue-exposure session. The VMPFC, amygdala and ventral striatum show habituation in response to drug-related cues which is consistent among different clinical populations. This habituated response in the first session of cue-exposure and lack of reactivity in the second session of exposure may be important for informing the development of cue-desensitization interventions.

A model-based quantification of startle reflex habituation in larval zebrafish.

Zebrafish is an established animal model for the reproduction and study of neurobiological pathogenesis of human neurological conditions. The 'startle reflex' in zebrafish larvae is an evolutionarily preserved defence response, manifesting as a quick body-bend in reaction to sudden sensory stimuli. Changes in startle reflex habituation characterise several neuropsychiatric disorders and hence represent an informative index of neurophysiological health. This study aimed at establishing a simple and reliable experimental protocol for the quantification of startle reflex response and habituation. The fish were stimulated with 20 repeated pulses of specific vibratory frequency, acoustic intensity/power, light-intensity and interstimulus-interval, in three separate studies. The cumulative distance travelled, namely the sum of the distance travelled (mm) during all 20 stimuli, was computed as a group-level description for all the experimental conditions in each study. Additionally, by the use of bootstrapping, the data was fitted to a model of habituation with a first-order exponential representing the decay of locomotor distance travelled over repeated stimulation. Our results suggest that startle habituation is a stereotypic first-order process with a decay constant ranging from 1 to 2 stimuli. Habituation memory lasts no more than 5 min, as manifested by the locomotor activity recovering to baseline levels. We further observed significant effects of vibratory frequency, acoustic intensity/power and interstimulus-interval on the amplitude, offset, decay constant and cumulative distance travelled. Instead, the intensity of the flashed light did not contribute to significant behavioural variations. The findings provide novel insights as to the influence of different stimuli parameters on the startle reflex habituation and constitute a helpful reference framework for further investigation.

Sympathetic contributions to habituation and recovery of the cardiac defense response.

The cardiac defense response (CDR) to intense auditory stimulation is characterized by two acceleration-deceleration heart rate (HR) components. This study investigated contributions of sympathetic cardiac control to habituation and recovery of the CDR. Fifty-six healthy subjects were presented with noise stimuli eliciting the CDR. Three stimuli were presented with short and long (2.5 min and 12.5 min) inter-trial intervals (ITIs). The pre-ejection period was recorded as an index of sympathetic cardiac control, in addition to HR. Repeated stimulation at short ITI was associated with marked habituation of the HR and sympathetic responses; both responses exhibited a degree of recovery with long ITI. Regarding the time course, the first acceleration-deceleration was accompanied by a decline and subsequent increase in sympathetic cardiac control. During the second acceleration-deceleration, the parameters exhibited parallel courses. These results suggest that the sympathetic contribution to the habituation and recovery is limited to the second HR component.

Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II.

The ACCURATE randomized, controlled trial compared outcomes of dorsal root ganglion (DRG) stimulation versus tonic spinal cord stimulation (SCS) in 152 subjects with chronic lower extremity pain due to complex regional pain syndrome (CRPS) type I or II. This ACCURATE substudy was designed to evaluate whether therapy habituation occurs with DRG stimulation as compared to SCS through 12-months. A modified intention-to-treat analysis was performed to assess percentage pain relief (PPR) and responder rates at follow-up visits (end-of-trial, 1, 3, 6, 9, 12-months postpermanent implant) for all subjects that completed trial stimulation (DRG:N = 73, SCS:N = 72). For both groups, mean PPR was significantly greater at end-of-trial (DRG = 82.2%, SCS =0 77.0%) than all other follow-ups. Following permanent DRG system implantation, none of the time points were significantly different from one another in PPR (range = 69.3-73.9%). For the SCS group, PPR at 9-months (58.3%) and 12-months (57.9%) was significantly less than at 1-month (66.9%). The responder rate also decreased for the SCS group from 1-month (68.1%) to 12-months (61.1%). After stratifying by diagnosis, it was found that only the CRPS-I population had diminishing pain relief with SCS. DRG stimulation resulted in more stable pain relief through 12-months, while tonic SCS demonstrated therapy habituation at 9- and 12-months. Trial Registration: The ACCURATE study was registered at ClinicalTrials.gov with Identifier NCT01923285. PERSPECTIVE: This article reports on an ACCURATE substudy, which found that long-term therapy habituation occurred at 12-months with SCS, but not DRG stimulation, in patients with CRPS. The underlying mechanisms of action for these results remain unclear, although several lines of inquiry are proposed.

Impaired P1 Habituation and Mismatch Negativity in Children with Autism Spectrum Disorder.

Passive testing of auditory function is an important objective in individuals with ASD due to known difficulties in understanding and/or following task instructions. In present study the habituation to standard tones following deviants and the auditory discriminative processes were examined in two conditions: electronic and human sounds, in a sample of 16 ASD children. ASD children presented a reduced habituation in the P1 component and a decrease in the amplitude of the mismatch negativity indicating a lower auditory discrimination with respect to controls. MMN amplitude was related to sensory sensitivity. Results suggest an increased activation to repeatedly auditory stimulus and a poor auditory discrimination, for both: electronic and human sounds with consequences on the impaired sensory behavior of ASD subjects.

Drosophila Bruton's Tyrosine Kinase Regulates Habituation Latency and Facilitation in Distinct Mushroom Body Neurons.

Habituation is the adaptive behavioral outcome of processes engaged in timely devaluation of non-reinforced repetitive stimuli, but the neuronal circuits and molecular mechanisms that underlie them are not well understood. To gain insights into these processes we developed and characterized a habituation assay to repetitive footshocks in mixed sex Drosophila groups and demonstrated that acute neurotransmission from adult α/ß mushroom body (MB) neurons prevents premature stimulus devaluation. Herein we demonstrate that activity of the non-receptor tyrosine kinase dBtk protein is required within these neurons to prevent premature habituation. Significantly, we also demonstrate that the complementary process of timely habituation to the repetitive stimulation is facilitated by α'/ß' MB neurons and also requires dBtk activity. Hence our results provide initial insights into molecular mechanisms engaged in footshock habituation within distinct MB neurons. Importantly, dBtk attenuation specifically within α'/ß' neurons leads to defective habituation, which is readily reversible by administration of the antipsychotics clozapine and risperidone suggesting that the loss of the kinase may dysregulate monoamine receptors within these neurons, whose activity underlies the failure to habituate.SIGNIFICANCE STATEMENT Habituation refers to processes underlying decisions to attend or ignore stimuli, which are pivotal to brain function as they underlie selective attention and learning, but the circuits involved and the molecular mechanisms engaged by the process therein are poorly understood. We demonstrate that habituation to repetitive footshock involves two phases mediated by distinct neurons of the Drosophila mushroom bodies and require the function of the dBtk non-receptor tyrosine kinase. Moreover, habituation failure upon dBtk abrogation in neurons where it is required to facilitate the process is readily reversible by antipsychotics, providing conceptual links to particular symptoms of schizophrenia in humans, also characterized by habituation defects and ameliorated by these pharmaceuticals.

Distinct Patterns of Neural Habituation and Generalization in Children and Adolescents With Autism With Low and High Sensory Overresponsivity.

OBJECTIVE: Sensory overresponsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in autism spectrum disorder (ASD). Previous work has related SOR to increased brain response in sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: arousal (i.e., initial response), habituation (i.e., change in response over time), and generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches. METHODS: Functional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning children and adolescents with ASD (21 with high levels of SOR and 21 with low levels of SOR) and 27 age-matched typically developing youths (ages 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined. RESULTS: Across repeated sensory stimulation, high-SOR participants with ASD showed reduced ability to maintain habituation in the amygdala and relevant sensory cortices and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, time-varying process dependent on sustained regulation across time, which is a particular deficit in high-SOR participants with ASD. However, low-SOR participants with ASD also showed distinct, nontypical neural response patterns, including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure. CONCLUSIONS: The results suggest that all children with autism have atypical brain responses to sensory stimuli, but whether they express atypical behavioral responses depends on top-down regulatory mechanisms. Results are discussed in terms of targeted intervention approaches.

Cognitive behavioral therapy, mindfulness, and cortisol habituation: A randomized controlled trial.

BACKGROUND: Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is associated with disease and may be indexed by poor cortisol habituation (i.e., a failure to show decreased responding with repeated stressor exposure). Thus, stress management training that can enhance HPA axis habituation may benefit health. To date, the effects of Mindfulness Based Stress Reduction (MBSR) and Cognitive Behavioral Therapy (CBT) interventions on HPA axis habituation remain untested. To test the effects of MBSR and CBT on HPA axis habituation, the present study used a parallel arm randomized controlled trial. METHODS: Healthy adults reporting moderate-to-high stress (n = 138) were randomly assigned to a 6-week MBSR intervention, a 6-week CBT intervention, or Waitlist control group. Post-intervention, participants completed a social-evaluative performance stressor during each of two laboratory visits scheduled 48-h apart. Salivary cortisol was collected pre-stressor, and 25, 35, and 60 min post-stressor onset during each visit. Final analyses included 86 participants who completed procedures up to the first laboratory visit. RESULTS: Relative to the control condition, both MBSR and CBT groups showed greater cortisol habituation. The MBSR group exhibited marginally greater habituation than the Waitlist group in cortisol samples corresponding to the recovery time points (35 and 60 min post-stressor onset). In contrast, the CBT group showed greater habituation than the Waitlist across all sampling timepoints collected (pre-stressor, 25, 35, and 60 min post-stressor onset). Yet, the CBT group also demonstrated elevated pre-stressor cortisol during the first visit. CONCLUSIONS: Results suggest that MBSR and CBT interventions promote greater HPA axis habituation relative to no training, but do not reduce overall cortisol output (i.e., across both visits). Observed differences between CBT and MBSR training in relation to cortisol habituation are discussed.

Habituation of the electrodermal response - A biological correlate of resilience?

Current approaches to quantifying resilience make extensive use of self-reported data. Problematically, this type of scales is plagued by response distortions-both deliberate and unintentional, particularly in occupational populations. The aim of the current study was to develop an objective index of resilience. The study was conducted in 30 young healthy adults. Following completion of the Connor-Davidson Resilience Scale (CD-RISC) and Depression/Anxiety/Stress Scale (DASS), they were subjected to a series of 15 acoustic startle stimuli (95 dB, 50 ms) presented at random intervals, with respiration, skin conductance and ECG recorded. As expected, resilience (CD-RISC) significantly and negatively correlated with all three DASS subscales-Depression (r = -0.66, p<0.0001), Anxiety (r = -0.50, p<0.005) and Stress (r = -0.48, p<0.005). Acoustic stimuli consistently provoked transient skin conductance (SC) responses, with SC slopes indexing response habituation. This slope significantly and positively correlated with DASS-Depression (r = 0.59, p<0.005), DASS-Anxiety (r = 0.35, p<0.05) and DASS-Total (r = 0.50, p<0.005) scores, and negatively with resilience score (r = -0.47; p = 0.006), indicating that high-resilience individuals are characterized by steeper habituation slopes compared to low-resilience individuals. Our key finding of the connection between habituation of the skin conductance responses to repeated acoustic startle stimulus and resilience-related psychometric constructs suggests that response habituation paradigm has the potential to characterize important attributes of cognitive fitness and well-being-such as depression, anxiety and resilience. With steep negative slopes reflecting faster habituation, lower depression/anxiety and higher resilience, and slower or no habituation characterizing less resilient individuals, this protocol may offer a distortion-free method for objective assessment and monitoring of psychological resilience.

Startle, pre-pulse sensitization, and habituation in zebrafish.

BACKGROUND: The startle response, pre-pulse presentation of startle, and habituation in adult zebrafish (danio rerio) have not been formerly characterized using the same motion detection equipment within an integrated procedure. NEW METHOD: The methods presented in this manuscript describe the use of a video tracking software used previously in the detection of conditioned immobility in rodents, but adapted for the purposes of tracking zebrafish movement. RESULTS: The results from a series of investigations demonstrate an effective tracking and quantification of the startle response, as well as evidence that stimulus-experience history alters the startle response in adult zebrafish. COMPARISON WITH EXISTING METHODS: This method of tracking zebrafish allows for the quantification on movement of a single subject, and the delivery of the startle stimulus can be synchronized with the motion-detection software to obtain a high temporal resolution that is not provided by other means of motion-detection tracking. CONCLUSION: Objective techniques for evaluating these basic modifications of the startle response (pre-pulse and habituation) may be helpful in future behavioral analysis as this species is rapidly becoming among the most commonly utilized in preclinical pharmacological assessment.

Acoustic prepulse inhibition in male and female prairie voles: Implications for models of neuropsychiatric illness.

Sensory gating, the ability to suppress sensory information of irrelevant stimuli, is affected in several neuropsychiatric diseases, notably schizophrenia and autism. It is currently unclear how these deficits interact with other hallmark symptoms of these disorders, such as social withdrawal and difficulty with interpersonal relationships. The highly affiliative prairie vole (Microtus ochrogaster) may be an ideal model organism to study the neurobiology underlying social behavior. In this study, we assessed unimodal acoustic sensory gating in male and female prairie voles using the prepulse inhibition (PPI) paradigm, whereby a lower amplitude sound (prepulse) decreases the startle response to a high amplitude sound (pulse) compared to the high amplitude sound alone. Prairie voles showed evidence of PPI at all prepulse levels compared to pulse alone, with both males and females showing similar levels of inhibition. However, unlike what has been reported in other rodent species, prairie voles did not show a within-session decrease in startle response to the pulse alone, nor did they show a decrease in startle response to the pulse over multiple days, highlighting their inability to habituate to startling stimuli (short- and long-term). When contrasted with a cohort of male wildtype C57Bl/6J mice that underwent a comparable PPI protocol, individual voles showed significantly higher trial-by-trial variability as well as longer latency to startle than mice. The benefits and caveats to using prairie voles in future sensory gating experiments are discussed.

Early enhanced processing and delayed habituation to deviance sounds in autism spectrum disorder.

Children with autism spectrum disorder (ASD) exhibit difficulties processing and encoding sensory information in daily life. Cognitive response to environmental change in control individuals is naturally dynamic, meaning it habituates or reduces over time as one becomes accustomed to the deviance. The origin of atypical response to deviance in ASD may relate to differences in this dynamic habituation. The current study of 133 children and young adults with and without ASD examined classic electrophysiological responses (MMN and P3a), as well as temporal patterns of habituation (i.e., N1 and P3a change over time) in response to a passive auditory oddball task. Individuals with ASD showed an overall heightened sensitivity to change as exhibited by greater P3a amplitude to novel sounds. Moreover, youth with ASD showed dynamic ERP differences, including slower attenuation of the N1 response to infrequent tones and the P3a response to novel sounds. Dynamic ERP responses were related to parent ratings of auditory sensory-seeking behaviors, but not general cognition. As the first large-scale study to characterize temporal dynamics of auditory ERPs in ASD, our results provide compelling evidence that heightened response to auditory deviance in ASD is largely driven by early sensitivity and prolonged processing of auditory deviance.

Oscillations Synchronize Amygdala-to-Prefrontal Primate Circuits during Aversive Learning.

The contribution of oscillatory synchrony in the primate amygdala-prefrontal pathway to aversive learning remains largely unknown. We found increased power and phase synchrony in the theta range during aversive conditioning. The synchrony was linked to single-unit spiking and exhibited specific directionality between input and output measures in each region. Although it was correlated with the magnitude of conditioned responses, it declined once the association stabilized. The results suggest that amygdala spikes help to synchronize ACC activity and transfer error signal information to support memory formation.

The More Vivid the Imagination the Better: The Role of the Vividness of Imagination in Vasoconstriction Training and Vasodilatation Training.

Blood volume pulse biofeedback represents an effective non-pharmacological treatment for migraine. However, the underlying mechanisms of blood volume pulse biofeedback are still unclear. This study investigated the influence of vividness of imagination, private body consciousness, perfectionism, and general self-efficacy on physiological (blood volume pulse amplitude) and psychological (session performance rated by participants and by trainers) success. Changes in skin conductance and skin temperature indicating habituation to training context were examined. Forty-five healthy male participants were randomized to four sessions of vasoconstriction training or vasodilatation training. Hierarchical linear models were estimated. Results showed significant changes of session performance rated by participants (UC = 0.62, p < .05), by trainers (UC = 0.52, p < .001), and skin temperature (UC = 0.01, p < .001) over time. A change of blood volume pulse amplitude could not be observed (UC = -0.01, p = .65). Vividness of imagination was highly important for both psychological achievement ratings (UC participants = 1.3, p < .001; UC trainers = 0.29, p < .01). Relations between skin temperature and general self-efficacy or personal standards were small (UC self-efficacy = 0.002, p < .10; UC personal standards = 0.002, p < .05). A time × group interaction regarding trainers' achievement ratings indicated a specific judgement effect. In conclusion, biofeedback trainers should pay attention to their beliefs and participants' vividness of imagination.

BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats.

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices. Furthermore, positive modulation of BK channels in vivo can enhance short-term habituation. Although results using different approaches do not always perfectly align, together they provide convincing evidence for a crucial role of BK channel phosphorylation in synaptic depression underlying short-term habituation of startle. We also show that this mechanism can be targeted to enhance short-term habituation and therefore to potentially ameliorate sensory filtering deficits associated with psychiatric disorders.SIGNIFICANCE STATEMENT Short-term habituation is the most fundamental form of implicit learning. Habituation also represents a filter for inundating sensory information, which is disrupted in autism, schizophrenia, and other psychiatric disorders. Habituation has been studied in different organisms and behavioral models and is thought to be caused by synaptic depression in respective pathways. The underlying molecular mechanisms, however, are poorly understood. We here identify, for the first time, a BK channel-dependent molecular synaptic mechanism leading to synaptic depression that is crucial for habituation, and we discuss the significance of our findings for potential treatments enhancing habituation.

Eyeblink conditioning with a noise burst as unconditioned stimulus.

BACKGROUND: The aim of this study was to determine if a white noise burst could be used as an effective unconditioned stimulus (US) to produce differential conditioning of eyeblink responses that were recorded as EMG activity of the orbicularis oculi. METHOD: Two fear-relevant stimuli served as conditioned stimuli (CS). An angry woman’s face (CS+) was consistently followed by a white noise burst (US) with 100 dB intensity and 100 milliseconds in duration.  A fearful face of the same woman (CS-) was not followed by the US. CS duration was 500 milliseconds (ms) for 18 participants (long interval group), and 250 ms for 19 participants (short interval group). The US was presented in both groups immediately after terminating CS+. RESULTS: The results showed acquisition of differential conditioning in the long interval group, but not in the short interval group. CONCLUSIONS: These results suggest that a white noise burst as US could be used in one single experimental procedure which was capable of simultaneously producing conditioning in neural, autonomic and somatomotor response systems.

Habituation of self-reported anxiety and cortical hyper-vigilance during image-based exposure to spiders.

BACKGROUND AND OBJECTIVES: The aim of the study was to examine habituation of subjective anxiety and electrophysiological correlates of cortical hyper-vigilance during exposure to spider images among high (n = 12) and low (n = 11) spider fear groups. METHODS: Participants viewed a six-stage hierarchy of spider images. The images used at stage 1 and stage 6 were the same. Subjective anxiety was rated at four intervals during each three-minute exposure stage (0, 60, 120, and 180 s) and event-related potentials (ERPs) were averaged across these epochs (0-60, 60-120, 120-180). RESULTS: High spider fearfuls demonstrated greater habituation of self-reported anxiety within and between exposure stages compared to low fearfuls. Consistent with attentional hyper-vigilance, the high-fear group also demonstrated greater P1 amplitude in response to spider images. In both groups, habituation of P1 amplitude was found at later relative to earlier stages, but increased at stage six when the stage 1 image was re-presented, despite low subjective anxiety. LIMITATIONS: While the passive viewing paradigm mirrored image-based exposure, it was not possible to determine whether participants engaged in avoidance strategies. In addition, further research is needed to assess the relevance of habituation and reinstatement of P1 amplitude to therapeutic outcome. CONCLUSIONS: Habituation of subjective anxiety during image-based exposure is not necessarily accompanied by a reduction in measures of cortical hyper-vigilance. The reinstatement of the P1 response may indicate either re-activation of previous associations, less avoidance, or a more generalised dishabituation mechanism.

Visual perception and visual mental imagery of emotional faces generate similar expression aftereffects.

What is the relationship between visual perception and visual mental imagery of emotional faces? We investigated this question using a within-emotion perceptual adaptation paradigm in which adaptation to a strong version of an expression was paired with a test face displaying a weak version of the same emotion category. We predicted that within-emotion adaptation to perception and imagery of expressions would generate similar aftereffects, biasing perception of weak emotional test faces toward a more neutral value. Our findings confirmed this prediction. Adaptation to mental images yielded aftereffects that inhibited emotion recognition of test expressions, as participants were less accurate at recognising these stimuli compared to baseline. While the same inhibitory effect was observed when expressions were visually perceived, the size of the aftereffects was greater for perception than imagery. These findings suggest the existence of expression-selective neural mechanisms that subserve both visual perception and visual mental imagery of emotional faces.

A large single ethnicity study of prepulse inhibition in schizophrenia: Separate analysis by sex focusing on effect of symptoms.

Deficits in sensorimotor gating, as measured with prepulse inhibition (PPI), have been considered an endophenotype of schizophrenia. However, the question remains whether these deficits are related to current symptoms. This single site study aimed to explore clinical features related to the modulation of startle reflex in a large sample of Japanese patients with schizophrenia (DSM-IV). The subjects comprised 181 patients and 250 healthy controls matched for age and sex. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Startle reflex to acoustic stimuli was recorded using a startle stimulus of 115 dB and a prepulse of four different conditions (intensity: 86 dB or 90 dB; lead interval: 60 ms or 120 ms). Patients exhibited significantly reduced startle magnitude (p < 0.001), habituation (p = 0.001), and PPI (90 dB, 60 ms, p = 0.016; 90 dB, 120 ms, p = 0.001) compared with controls. Patients of both sexes exhibited significantly lower habituation and PPI (90 dB, 120 ms) compared with the same sex controls. We could not detect a significant correlation with any clinical variable in the entire patients, however, when men and women were examined separately, there was a negative correlation with the PANSS cognitive domain (ρ = -0.33, p = 0.008) in men, but not in women. Moreover, when patients were subdivided into four clusters, two clusters with high positive symptoms showed significant PPI deficits in men. Our results suggest that sensorimotor gating is impaired in schizophrenia of both sexes, and PPI deficits may be related to thought disturbance and disorganization in male patients with schizophrenia.