That sounds awful! Does sound unpleasantness modulate the mismatch negativity and its habituation?

There are sounds that most people perceive as highly unpleasant, for instance, the sound of rubbing pieces of polystyrene together. Previous research showed larger physiological and neural responses for such aversive compared to neutral sounds. Hitherto, it remains unclear whether habituation, i.e., diminished responses to repeated stimulus presentation, which is typically reported for neutral sounds, occurs to the same extent for aversive stimuli. We measured the mismatch negativity (MMN) in response to rare occurrences of aversive or neutral deviant sounds within an auditory oddball sequence in 24 healthy participants, while they performed a demanding visual distractor task. Deviants occurred as single events (i.e., between two standards) or as double deviants (i.e., repeating the identical deviant sound in two consecutive trials). All deviants elicited a clear MMN, and amplitudes were larger for aversive than for neutral deviants (irrespective of their position within a deviant pair). This supports the claim of preattentive emotion evaluation during early auditory processing. In contrast to our expectations, MMN amplitudes did not show habituation, but increased in response to deviant repetition-similarly for aversive and neutral deviants. A more fine-grained analysis of individual MMN amplitudes in relation to individual arousal and valence ratings of each sound item revealed that stimulus-specific MMN amplitudes were best predicted by the interaction of deviant position and perceived arousal, but not by valence. Deviants with perceived higher arousal elicited larger MMN amplitudes only at the first deviant position, indicating that the MMN reflects preattentive processing of the emotional content of sounds.

Accessible and reliable neurometric testing in humans using a smartphone platform.

Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, prepulse inhibition of acoustic startle response, and startle habituation. This approach provides a scalable, universal resource for quantitative assays of central nervous system function.

Effects of iron supplementation on neural indices of habituation in Bangladeshi children.

BACKGROUND: Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. OBJECTIVE: We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). METHODS: This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. RESULTS: Data were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07µV [95% CI: -1.22, 1.37]; MNPs compared with placebo: MD = 0.58µV [95% CI: -0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. CONCLUSION: In Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.

Dispositional mindfulness, alexithymia and sensory processing: Emerging insights from habituation of the acoustic startle reflex response.

There is growing evidence of beneficial effects of mindfulness developed through engaging in mindfulness training/practices on sensory and cognitive processing, emotion regulation and mental health. Mindfulness has also been conceptualised as a dispositional 'trait', i.e. the naturally-occurring ability of meditation-naïve individuals to display, in varying degree, a non-judgmental non-reactive present-moment awareness in everyday life. In this study we examined possible associations between dispositional mindfulness, alexithymia and sensory processing. Eye-blink startle responses to acoustic stimuli of varying intensity [90-dB or 100-dB over 70-dB (A) background] were assessed in 26 meditation-naïve adults (50 % men) using electromyographic recordings of the orbicularis muscle. All participants completed the Five Facet Mindfulness Questionnaire and the 20-item Toronto Alexithymia Scale. A negative association was found between dispositional mindfulness and alexithymia (r = -0.513). There was stronger startle habituation to 100-dB, compared to 90-dB probes. Stronger startle habituation (larger negative habitation slope values) to 100-dB probes was significantly associated with higher dispositional mindfulness (r = -0.528) and with lower alexithymia at trend level (r = 0.333). As indicated by commonality analysis, 10.6 % of explained variance in habituation (100-dB probes) was common to both alexithymia and mindfulness, 17.3 % was unique to mindfulness, but alexithymia made negligible unique contribution (0.5 %). These findings indicate similar startle habituation pattern in people with a high level of dispositional mindfulness to that reported previously by Antonova et al. (2015) in people with moderate mindfulness meditation practice intensity. Future studies should investigate the mechanisms, such as interoceptive awareness, that might underly these relationships.

cacna2d3, a voltage-gated calcium channel subunit, functions in vertebrate habituation learning and the startle sensitivity threshold.

BACKGROUND: The ability to filter sensory information into relevant versus irrelevant stimuli is a fundamental, conserved property of the central nervous system and is accomplished in part through habituation learning. Synaptic plasticity that underlies habituation learning has been described at the cellular level, yet the genetic regulators of this plasticity remain poorly understood, as do circuits that mediate sensory filtering. METHODS: To identify genes critical for plasticity, a forward genetic screen for zebrafish genes that mediate habituation learning was performed, which identified a mutant allele, doryp177, that caused reduced habituation of the acoustic startle response. In this study, we combine whole-genome sequencing with behavioral analyses to characterize and identify the gene affected in doryp177 mutants. RESULTS: Whole-genome sequencing identified the calcium voltage-gated channel auxiliary subunit alpha-2/delta-3 (cacna2d3) as a candidate gene affected in doryp177 mutants. Behavioral characterization of larvae homozygous for two additional, independently derived mutant alleles of cacna2d3, together with failure of these alleles to complement doryp177, confirmed a critical role for cacna2d3 in habituation learning. Notably, detailed analyses of the acoustic response in mutant larvae also revealed increased startle sensitivity to acoustic stimuli, suggesting a broader role for cacna2d3 in controlling innate response thresholds to acoustic stimuli. CONCLUSIONS: Taken together, our data demonstrate a critical role for cacna2d3 in sensory filtering, a process that is disrupted in human CNS disorders, e.g. ADHD, schizophrenia, and autism.

Hyperreactivity and Impaired Habituation of Startle Amplitude During Unpleasant Pictures in Borderline but Not Schizotypal Personality Disorder: Quantifying Emotion Dysregulation.

BACKGROUND: Borderline personality disorder (BPD) is characterized by greater intensity of reactions to unpleasant emotional cues and a slower-than-normal return of these responses to baseline. Habituation is defined as decreased response to repeated stimulation. Affect-modulated startle (AMS), a translational psychophysiological approach, is mediated by the amygdala and used to study emotion processing in both humans and animals. This is the first study to examine the specificity of habituation anomalies in BPD during passive emotional and neutral picture processing. METHODS: A total of 90 participants were studied: patients with BPD (n = 35), patients with schizotypal personality disorder (n = 26; included as a psychopathological comparison group), and healthy control subjects (n = 29). Participants received rigorous clinical assessments, and patients were unmedicated. AMS was examined during a series of intermixed unpleasant, neutral, and pleasant pictures. RESULTS: Compared with the other groups, patients with BPD showed greater overall AMS during unpleasant pictures and prolonged habituation of startle amplitude during unpleasant pictures from early to later trials. The groups did not differ in AMS during neutral or pleasant pictures or self-reported picture valence. Among the patients with BPD, prolonged habituation to unpleasant pictures was associated with greater symptom severity and suicidal/self-harming behavior. CONCLUSIONS: These findings 1) indicate that abnormal processing of and habituation to unpleasant pictures is observed in BPD but not schizotypal personality disorder, suggesting that these deficits are not simply characteristics of personality disorders in general; 2) are consistent with studies showing deficient amygdala habituation to unpleasant pictures in BPD; and 3) have significant implications for clinical assessment and treatment of BPD, e.g., alternative therapies for BPD such as gradual exposure to unpleasant emotional stimuli or amygdala neurofeedback may aid habituation deficits.

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.

Prepulse inhibition deficits in inbred and outbred rats and between-strain differences in startle habituation do not depend on startle reactivity levels.

The acoustic startle response and prepulse inhibition (PPI) of startle are measures related to information processing, which is impaired in schizophrenia. Some studies have provided inconclusive patterns of association between both measures in rodents. We assessed the influence of baseline startle response on PPI in large samples of Roman high-(RHA) and low-avoidance (RLA) rat strains and in genetically heterogeneous stock (HS) rats. Results show that RHAs exhibit a PPI deficit compared to RLA rats, which is present regardless of the startle response levels. HS rats were stratified in two sub-samples according to their high or low PPI (HS-highPPI or HS-lowPPI, respectively) scores, and then they were grouped by their differential baseline startle amplitude (high reactivity -HR- or low reactivity -LR-) within each sub-sample. Differences between high- and low-PPI-stratified HS rats remained regardless of their high or low startle amplitude scores. Thus, the impairments in %PPI found in both RHA and HS-LowPPI rats are present irrespective of the relatively high or low levels of startle amplitude in pulse-alone trials. Another objective of the present study was to evaluate whether habituation to the startling stimulus (i.e., pulse) depends on the initial baseline startle response. RLA rats habituated to the startling stimulus more effectively than RHAs regardless of their baseline startle responses. Conversely, there were no differences in startle habituation in the HS rats grouped by their extreme scores of baseline startle. Altogether, these findings suggest a deficit in information processing in RHA rats, which along with evidence indicating that this strain displays other attentional/cognitive impairments, strengthens the validity of the RHA strain as a putative model of schizophrenia-relevant features.

Feasibility of motor imagery and effects of activating and relaxing practice on autonomic functions in healthy young adults: A randomised, controlled, assessor-blinded, pilot trial.

INTRODUCTION: Motor imagery (MI) is the mental rehearsal of a motor task. Between real and imagined movements, a functional equivalence has been described regarding timing and brain activation. The primary study aim was to investigate the feasibility of MI training focusing on the autonomic function in healthy young people. Further aims were to evaluate participants' MI abilities and compare preliminary effects of activating and relaxing MI on autonomic function and against controls. METHODS: A single-blinded randomised controlled pilot trial was performed. Participants were randomised to the activating MI (1), relaxing MI (2), or control (3) group. Following a MI familiarisation, they practiced home-based kinaesthetic MI for 17 minutes, 5 times/week for 2 weeks. Participants were called once for support. The primary outcome was the feasibility of a full-scale randomised controlled trial using predefined criteria. Secondary outcomes were participants' MI ability using the Movement Imagery Questionnaire-Revised, mental chronometry tests, hand laterality judgement and semi-structured interviews, autonomic function. RESULTS: A total of 35 participants completed the study. The feasibility of a larger study was confirmed, despite 35% attrition related to the COVID-19 pandemic. Excellent MI capabilities were seen in participants, and significant correlations between MI ability measures. Interview results showed that participants accepted or liked both interventions. Seven major themes and insider recommendations for MI interventions emerged. No significant differences and negligible to medium effects were observed in MI ability or autonomic function between baseline and post-intervention measures or between groups. CONCLUSIONS: Results showed that neither activating nor relaxing MI seems to change autonomic function in healthy individuals. Further adequately powered studies are required to answer open questions remaining from this study. Future studies should investigate effects of different MI types over a longer period, to rule out habituation and assess autonomic function at several time points and simultaneously with MI.

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.

Subcellular Dissection of a Simple Neural Circuit: Functional Domains of the Mauthner-Cell During Habituation.

Sensorimotor integration is a pivotal feature of the nervous system for ensuring a coordinated motor response to external stimuli. In essence, such neural circuits can optimize behavioral performance based on the saliency of environmental cues. In zebrafish, habituation of the acoustic startle response (ASR) is a simple behavior integrated into the startle command neurons, called the Mauthner cells. Whereas the essential neuronal components that regulate the startle response have been identified, the principles of how this regulation is integrated at the subcellular regions of the Mauthner cell, which in turn modulate the performance of the behavior, is still not well understood. Here, we reveal mechanistically distinct dynamics of excitatory inputs converging onto the lateral dendrite (LD) and axon initial segment (AIS) of the Mauthner cell by in vivo imaging glutamate release using iGluSnFR, an ultrafast glutamate sensing fluorescent reporter. We find that modulation of glutamate release is dependent on NMDA receptor activity exclusively at the AIS, which is responsible for setting the sensitivity of the startle reflex and inducing a depression of synaptic activity during habituation. In contrast, glutamate-release at the LD is not regulated by NMDA receptors and serves as a baseline component of Mauthner cell activation. Finally, using in vivo calcium imaging at the feed-forward interneuron population component of the startle circuit, we reveal that these cells indeed play pivotal roles in both setting the startle threshold and habituation by modulating the AIS of the Mauthner cell. These results indicate that a command neuron may have several functionally distinct regions to regulate complex aspects of behavior.

Single dose testosterone administration enhances novelty responsiveness and short-term habituation in healthy males.

The role of testosterone in sensory perception suggests that testosterone likely regulates adaptive responses to sensory changes, including habituation to repeated events and responsiveness to novel events. To test this hypothesis, we investigated how testosterone modulates brain responses to rapid changes in sensory inputs. Using a double-blind, placebo-controlled, within-participant design, each participant received a single dose of either testosterone or placebo, and then completed a passive auditory oddball task in which infrequent deviant tones were embedded in a series of frequent standard tones. Analysis of novelty-evoked potentials revealed smaller Mismatch Negativity (MMN) responses, but larger P3a responses in the testosterone session than in the placebo session. This suggests testosterone attenuates MMN responses that are associated with pre-attentive novelty detection and enhances P3a responses that are associated with involuntary attentional orientation toward novelty. Along with the repetition of standard tones, P2 responses on the auditory evoked potentials became significantly attenuated in the testosterone session, but not in the placebo session. This suggests testosterone enhances short-term habituation of P2 responses to recurring sensory events, which has been associated with bottom-up attention allocation. Mediation analysis further revealed that the role of testosterone in promoting attentional orientation toward novelty could be explained by the influence it exerts on short-term habituation and pre-attentive novelty detection. Overall, testosterone facilitated involuntary attention switching-withdrawal of attention from repeated sensory events and orientation toward novel sensory events-at the cost of attenuated pre-attentive novelty detection. This finding provides insight into the interplay between endocrinology and involuntary attentional processes.

Disrupted sensorimotor gating in first-episode psychosis patients is not affected by short-term antipsychotic treatment.

BACKGROUND: Impaired sensorimotor gating, commonly measured as disrupted prepulse inhibition (PPI) of the acoustic startle response, has been widely observed in psychotic diseases. However, most PPI studies published so far involve patients with long illness duration and different drug treatments. Few studies have investigated untreated patients at their first episode of psychotic symptoms. METHOD: PPI is an acoustic startle paradigm (30, 60-, 120-ms interstimulus intervals). Startle reactivity and habituation were succesfully assessed in 49 antipsychotic-naïve first-episode psychosis (FEP) patients and compared with 35 age- and gender-matched healthy control subjects. Mean age of patients was 28 years and 27 for controls. Patients treated with antipsychotics more than 30 days were not included in the study and twenty-three out of forty-nine patients received antipsychotic treatment with a mean treatment time of 13 days. RESULTS: PPI was significantly lower in FEP patients, compared to healthy controls. The PPI deficiency found in these patients was not due to antipsychotic treatment since PPI did not differ between treated (n=23) and untreated patients n=(26). By using the latent curve modeling we identified a delayed habituation in patients treated with antipsychotics, suggesting that antipsychotic treatment should be considered as a confound when investigating habituation in schizophrenia. CONCLUSIONS: Our results suggest that acute pharmacological treatment does not normalize PPI in FEP patients but should be considered as a confound when investigating habituation in these patients.

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.

Folic acid prevents habituation memory impairment and oxidative stress in an aging model induced by D-galactose.

The present study aimed to evaluate the effect of folic acid treatment in an animal model of aging induced by D-galactose (D-gal). For this propose, adult male Wistar rats received D-gal intraperitoneally (100 mg/kg) and/or folic acid orally (5 mg/kg, 10 mg/kg or 50 mg/kg) for 8 weeks. D-gal caused habituation memory impairment, and folic acid (10 mg/kg and 50 mg/kg) reversed this effect. However, folic acid 50 mg/kg per se caused habituation memory impairment. D-gal increased the lipid peroxidation and oxidative damage to proteins in the prefrontal cortex and hippocampus from rats. Folic acid (5 mg/kg, 10 mg/kg, or 50 mg/kg) partially reversed the oxidative damage to lipids in the hippocampus, but not in the prefrontal cortex, and reversed protein oxidative damage in the prefrontal cortex and hippocampus. D-gal induced synaptophysin and BCL-2 decrease in the hippocampus and phosphorylated tau increase in the prefrontal cortex. Folic acid was able to reverse these D-gal-related alterations in the protein content. The present study shows folic acid supplementation as an alternative during the aging to prevent cognitive impairment and brain alterations that can cause neurodegenerative diseases. However, additional studies are necessary to elucidate the effect of folic acid in aging.

Rapid Effects of Selection on Brain-wide Activity and Behavior.

Interindividual variation in behavior and brain activity is universal and provides substrates for natural selection [1-9]. Selective pressures shift the expression of behavioral traits at the population level [10, 11], but the accompanying changes of the underlying neural circuitry have rarely been identified [12, 13]. Selection likely acts through the genetic and/or epigenetic underpinnings of neural activity controlling the selected behavior [14]. Endocrine and neuromodulatory systems participate in behavioral diversity and could provide the substrate for evolutionary modifications [15-21]. Here, we examined brain-wide patterns of activity in larval zebrafish selectively bred over two generations for extreme differences in habituation of the acoustic startle response (ASR) [22]. The ASR is an evolutionarily conserved defensive behavior induced by strong acoustic/vibrational stimuli. ASR habituation shows great individual variability that is stable over days and heritable [4, 22]. Selection for high ASR habituation leads to stronger sound-evoked activation of ASR-processing brain areas. In contrast, animals selected for low habituation displayed stronger spontaneous activity in ASR-processing centers. Ablation of dopaminergic tyrosine hydroxylase (TH) neurons decreased ASR sensitivity. Independently selected ASR habituation lineages link the effect of behavioral selection to dopaminergic caudal hypothalamus (HC) neurons [23]. High ASR habituation co-segregated with decreased spontaneous swimming phenotypes, but visual startle responses were unaffected. Furthermore, high- and low-habituation larvae differed in stress responses as adults. Thus, selective pressure over a couple of generations on ASR habituation behavior is able to induce substantial differences in brain activity, carrying along additional behaviors as piggyback traits that might further affect fitness in the wild. VIDEO ABSTRACT.

Response to change in the number of visual stimuli in zebrafish:A behavioural and molecular study.

Evidence has shown that a variety of vertebrates, including fish, can discriminate collections of visual items on the basis of their numerousness using an evolutionarily conserved system for approximating numerical magnitude (the so-called Approximate Number System, ANS). Here we combine a habituation/dishabituation behavioural task with molecular biology assays to start investigating the neural bases of the ANS in zebrafish. Separate groups of zebrafish underwent a habituation phase with a set of 3 or 9 small red dots, associated with a food reward. The dots changed in size, position and density from trial to trial but maintained their numerousness, and the overall areas of the stimuli was kept constant. During the subsequent dishabituation test, zebrafish faced a change (i) in number (from 3 to 9 or vice versa with the same overall surface), or (ii) in shape (with the same overall surface and number), or (iii) in size (with the same shape and number). A control group of zebrafish was shown the same stimuli as during the habituation. RT-qPCR revealed that the telencephalon and thalamus were characterized by the most consistent modulation of the expression of the immediate early genes c-fos and egr-1 upon change in numerousness; in contrast, the retina and optic tectum responded mainly to changes in stimulus size.

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.