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Scientific Reports Apr 2023Recent primate studies have implicated a substantial role of reticulospinal pathways in the production of various voluntary movements. A novel way to assess the relative...
Recent primate studies have implicated a substantial role of reticulospinal pathways in the production of various voluntary movements. A novel way to assess the relative reticulospinal contributions in humans is through the use of a "StartReact" paradigm where a startling acoustic stimulus (SAS) is presented during a simple reaction time (RT) task. The StartReact response is characterized by short-latency triggering of a prepared response, which is attributed to increased reticulospinal drive associated with startle reflex activation. The current study used a StartReact protocol to examine differences in reticulospinal contributions between proximal and distal effectors by examining EMG onset latencies in lateral deltoid and first dorsal interosseous during bilateral shoulder or finger abduction. The magnitude of the StartReact effect, and thus relative reticulospinal drive, was quantified as the difference in RT between startle trials in which startle-reflex related EMG activation in the sternocleidomastoid (SCM) was present (SCM +) versus absent (SCM -). A significantly larger StartReact effect was observed for bilateral shoulder abduction versus bimanual finger abduction and a higher incidence of SCM + trials occurred in the proximal task. Additionally, both startle reflex and response-related EMG measures were larger on SCM + trials for the shoulder versus finger task. These results provide compelling novel evidence for increased reticulospinal activation in bilateral proximal upper-limb movements.
Topics: Humans; Shoulder; Electromyography; Reflex, Startle; Movement; Upper Extremity; Reaction Time; Acoustic Stimulation; Muscle, Skeletal
PubMed: 37085607
DOI: 10.1038/s41598-023-33493-5 -
Turkish Journal of Medical Sciences Jun 2021Sleep deprivation disrupts prepulse inhibition of acoustic startle reflex and can be used to mimic psychosis in ex- perimental animals. On the other hand, it is also a...
BACKGROUND/AIM
Sleep deprivation disrupts prepulse inhibition of acoustic startle reflex and can be used to mimic psychosis in ex- perimental animals. On the other hand, it is also a model for other disorders of sensory processing, including migraine. This study aims to assess the effects of sodium valproate, a drug that is used in a variety of neuropsychiatric disorders, on normal and disrupted sensorimotor gating in rats.
MATERIALS AND METHODS
Sixty-two Wistar albino rats were randomly distributed into 8 groups. Subchronic and intraperitoneal sodium valproate were administrated to the sleep-deprived and nonsleep-deprived rats by either 50–100 or 200 mg/kg/day. Prepulse inhibition test and locomotor activity test were performed. Sleep deprivation induced by the modified multiple platform method.
RESULTS
Sleep deprivation impaired prepulse inhibition, decreased startle amplitude, and increased locomotor activity. Sodium valpro- ate did not significantly alter prepulse inhibition and locomotor activity in nonsleep-deprived and sleep-deprived groups. On the other hand, all doses decreased locomotor activity in drug-treated groups, and low dose improved sensorimotor gating and startle amplitude after sleep deprivation.
CONCLUSION
Low-dose sodium valproate improves sleep deprivation-disrupted sensorimotor gating, and this finding may rationalize the use of sodium valproate in psychotic states and other sensory processing disorders. Dose-dependent effects of sodium valproate on sensorimotor gating should be investigated in detail.
Topics: Animals; Pharmaceutical Preparations; Rats; Rats, Wistar; Reflex, Startle; Sensory Gating; Sleep Deprivation; Valproic Acid
PubMed: 33517611
DOI: 10.3906/sag-2011-229 -
Brain : a Journal of Neurology Jul 2020Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined...
Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined unresponsive wakefulness syndrome (UWS)-and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15-20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.
Topics: Adult; Brain; Female; Habituation, Psychophysiologic; Humans; Male; Middle Aged; Persistent Vegetative State; Recovery of Function; Reflex, Startle
PubMed: 32582938
DOI: 10.1093/brain/awaa159 -
Psychophysiology Sep 2019A stimulus (conditioned stimulus, CS) associated with an appetitive unconditioned stimulus (US) acquires positive properties and elicits appetitive conditioned responses...
A stimulus (conditioned stimulus, CS) associated with an appetitive unconditioned stimulus (US) acquires positive properties and elicits appetitive conditioned responses (CR). Such associative learning has been examined extensively in animals with food as the US, and results are used to explain psychopathologies (e.g., substance-related disorders or obesity). Human studies on appetitive conditioning exist, too, but we still know little about generalization processes. Understanding these processes may explain why stimuli not associated with a drug, for instance, can elicit craving. Forty-seven hungry participants underwent an appetitive conditioning protocol during which one of two circles with different diameters (CS+) became associated with an appetitive US (chocolate or salty pretzel, according to participants' preference) but never the other circle (CS-). During generalization, US were delivered twice and the two CS were presented again plus four circles (generalization stimuli, GS) with gradually increasing diameters from CS- to CS+. We found successful appetitive conditioning as reflected in appetitive subjective ratings (positive valence, higher contingency) and physiological responses (startle attenuation and larger skin conductance responses) to CS+ versus CS-, and, importantly, both measures confirmed generalization as indicated by generalization gradients. Small changes in CS-US contingency during generalization may have weakened generalization processes on the physiological level. Considering that appetitive conditioned responses can be generalized to non-US-associated stimuli, a next important step would be to investigate risk factors that mediate overgeneralization.
Topics: Adolescent; Adult; Conditioning, Classical; Female; Food; Generalization, Psychological; Humans; Hunger; Male; Reflex, Startle; Reinforcement, Psychology; Young Adult
PubMed: 31152454
DOI: 10.1111/psyp.13397 -
British Journal of Clinical Pharmacology May 2017Centrally-acting acutely anxiolytic drugs, such as benzodiazepines, barbiturates and gabapentinoids, affect various central nervous system (CNS) functions, which... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIM
Centrally-acting acutely anxiolytic drugs, such as benzodiazepines, barbiturates and gabapentinoids, affect various central nervous system (CNS) functions, which reflects not only their anxiolytic effects but also neuropsychological side-effects. To validate the pharmacodynamic biomarkers for GABA-ergic anxiolytics, this study determined the pharmacodynamics of two anxiolytics and a nonanxiolytic control, and linked them to their anxiolytic and sedative effects, during an anxiety-challenge study day.
METHODS
Twenty healthy volunteers were randomized in this placebo-controlled, double-blind, four-way cross-over study with single-dose alprazolam (1 mg), diphenhydramine (50 mg), pregabalin (200 mg) or placebo. The Neurocart was used between repeated fear-potentiated startle assessments. Thus, the potential influence of anxiety on CNS pharmacodynamic markers could be examined.
RESULTS
Compared to placebo, VAS increased with alprazolam (2.0 mm) and pregabalin (2.5 mm) but not with diphenhydramine. Saccadic peak velocity (SPV) declined after alprazolam (-57 ° s ) and pregabalin (-28 ° s ), more than with diphenhydramine (-14 ° s ); so did smooth pursuit. The average responses of SPV and smooth pursuit were significantly correlated with the drug-induced increases in VAS . The SPV-relative responses of VAS , body-sway and adaptive-tracking also differed among alprazolam, pregabalin and diphenhydramine.
CONCLUSIONS
Compared with the antihistaminergic sedative diphenhydramine, alprazolam and pregabalin caused larger SPV reduction, which was correlated with simultaneous improvement of subjective calmness, during a study day in which anxiety was stimulated repeatedly. The different effect profiles of the three drugs are in line with their pharmacological distinctions. These findings corroborate the profiling of CNS effects to demonstrate pharmacological selectivity, and further support SPV as biomarker for anxiolysis involving GABA-ergic neurons. The study also supports the use of prolonged mild threat to demonstrate anxiolytic effects in healthy volunteers.
Topics: Adolescent; Adult; Alprazolam; Anti-Anxiety Agents; Anxiety; Biomarkers; Cross-Over Studies; Diphenhydramine; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Pregabalin; Reflex, Startle; Saccades; Young Adult; gamma-Aminobutyric Acid
PubMed: 27922194
DOI: 10.1111/bcp.13204 -
Journal of Visualized Experiments : JoVE Jul 2017The purpose of this protocol is to explain how to examine the relationship between working memory processes and anxiety by combining the Sternberg Working Memory (WM)...
The purpose of this protocol is to explain how to examine the relationship between working memory processes and anxiety by combining the Sternberg Working Memory (WM) and the threat of shock paradigms. In the Sternberg WM paradigm, subjects are required to maintain a series of letters in the WM for a brief interval and respond by identifying whether the position of a given letter in the series matches a numerical prompt. In the threat of shock paradigm, subjects are exposed to alternating blocks where they are either at risk of receiving unpredictable presentations of a mild electric shock or are safe from the shock. Anxiety is probed throughout the safe and threat blocks using the acoustic startle reflex, which is potentiated under threat (Anxiety-Potentiated Startle (APS)). By conducting the Sternberg WM paradigm during the threat of shock and probing the startle response during either the WM maintenance interval or the intertrial interval, it is possible to determine the effect of WM maintenance on APS.
Topics: Anxiety; Fear; Female; Humans; Male; Memory, Short-Term; Reflex, Startle
PubMed: 28745646
DOI: 10.3791/55727 -
Molecular Psychiatry Mar 2022Sensorimotor information processing underlies normal cognitive and behavioral traits and has classically been evaluated through prepulse inhibition (PPI) of a startle...
Sensorimotor information processing underlies normal cognitive and behavioral traits and has classically been evaluated through prepulse inhibition (PPI) of a startle reflex. PPI is a behavioral dimension deregulated in several neurological and psychiatric disorders, yet the mechanisms underlying the cross-diagnostic nature of PPI deficits across these conditions remain to be understood. To identify circuitry mechanisms for PPI, we performed circuitry recording over the prefrontal cortex and striatum, two brain regions previously implicated in PPI, using wild-type (WT) mice compared to Disc1-locus-impairment (LI) mice, a model representing neuropsychiatric conditions. We demonstrated that the corticostriatal projection regulates neurophysiological responses during the PPI testing in WT, whereas these circuitry responses were disrupted in Disc1-LI mice. Because our biochemical analyses revealed attenuated brain-derived neurotrophic factor (Bdnf) transport along the corticostriatal circuit in Disc1-LI mice, we investigated the potential role of Bdnf in this circuitry for regulation of PPI. Virus-mediated delivery of Bdnf into the striatum rescued PPI deficits in Disc1-LI mice. Pharmacologically augmenting Bdnf transport by chronic lithium administration, partly via phosphorylation of Huntingtin (Htt) serine-421 and its integration into the motor machinery, restored striatal Bdnf levels and rescued PPI deficits in Disc1-LI mice. Furthermore, reducing the cortical Bdnf expression negated this rescuing effect of lithium, confirming the key role of Bdnf in lithium-mediated PPI rescuing. Collectively, the data suggest that striatal Bdnf supply, collaboratively regulated by Htt and Disc1 along the corticostriatal circuit, is involved in sensorimotor gating, highlighting the utility of dimensional approach in investigating pathophysiological mechanisms across neuropsychiatric disorders.
Topics: Animals; Brain-Derived Neurotrophic Factor; Corpus Striatum; Humans; Mice; Nerve Tissue Proteins; Prefrontal Cortex; Prepulse Inhibition; Reflex, Startle; Sensory Gating
PubMed: 35165396
DOI: 10.1038/s41380-021-01389-3 -
The Journal of Experimental Biology Mar 2020The acoustic startle reflex is an oligo-synaptic reflex arc elicited by rapid-onset sounds. Odontocetes evolved a range of specific auditory adaptations to aquatic...
The acoustic startle reflex is an oligo-synaptic reflex arc elicited by rapid-onset sounds. Odontocetes evolved a range of specific auditory adaptations to aquatic hearing and echolocation, e.g. the ability to downregulate their auditory sensitivity when emitting clicks. However, it remains unclear whether these adaptations also led to changes of the startle reflex. We investigated reactions to startling sounds in two bottlenose dolphins () and one false killer whale (). Animals were exposed to 50 ms, 1/3 octave band noise pulses of varying levels at frequencies of 1, 10, 25 and 32 kHz while positioned in a hoop station. Startle responses were quantified by measuring rapid muscle contractions using a three-dimensional accelerometer attached to the dolphin. Startle magnitude increased exponentially with increasing received levels. Startle thresholds were frequency dependent and ranged from 131 dB at 32 kHz to 153 dB at 1 kHz (re. 1 µPa). Startle thresholds only exceeded masked auditory AEP thresholds of the animals by 47 dB but were ∼82 dB above published behavioural audiograms for these species. We also tested the effect of stimulus rise time on startle magnitude using a broadband noise pulse. Startle responses decreased with increasing rise times from 2 to 100 ms. Models suggested that rise times of 141-220 ms were necessary to completely mitigate startle responses. Our data showed that the startle reflex is conserved in odontocetes and follows similar principles as in terrestrial mammals. These principles should be considered when assessing and mitigating the effects of anthropogenic noise on marine mammals.
Topics: Acoustic Stimulation; Animals; Auditory Threshold; Bottle-Nosed Dolphin; Dolphins; Echolocation; Female; Hawaii; Male; Reflex, Startle
PubMed: 32165452
DOI: 10.1242/jeb.208470 -
Developmental Psychobiology May 2023The ability to anticipate and process predictable unpleasant events, while also regulating emotional reactivity, is an adaptive skill. The current article and a...
Neurophysiology of predictable unpleasant event processing in pre-adolescents and early adolescents, part II: Reflex and event-related potential markers of defensive reactivity and peripheral attention modulation.
The ability to anticipate and process predictable unpleasant events, while also regulating emotional reactivity, is an adaptive skill. The current article and a companion in this issue test for potential changes in predictable event processing across the childhood-to-adolescence transition, a key developmental period for biological systems that support cognitive/ emotional abilities. While the companion article focuses on neurophysiology of predictable event processing itself, the present article examines peripheral emotional response regulation and attention modulation that coincides with event processing. A total of 315 third-, sixth-, or ninth-grade individuals saw 5-s cues predicting "scary," "every day," or uncertain pictures, and here, blink reflexes and brain event-related potentials (ERPs) elicited by peripheral noise probes are analyzed. During the cue, blink reflexes and probe ERP (P200) amplitudes were increased when the cue predicted scary, compared to everyday, content. After picture onset, reflex enhancement by scary content then disappeared for predictable images, whereas ERP modulation was similar regardless of predictability. Patterns are similar to those in adults and suggest (1) sustained defensive response priming and enhancement of peripheral attention during aversive anticipation, and (2) an ability, even in pre-adolescents, to downregulate defensive priming while maintaining attentional modulation once an awaited predictable aversive event occurs.
Topics: Adult; Humans; Adolescent; Child; Reflex, Startle; Photic Stimulation; Evoked Potentials; Emotions; Attention; Electroencephalography
PubMed: 37073586
DOI: 10.1002/dev.22386 -
PloS One 2022Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental,...
Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle responses to threat which normalise when dystrophin is restored in the brain. We hypothesised that startle responses may also be increased in humans with DMD, which would have potential translational therapeutic implications. To investigate this, we first designed a novel discrimination fear-conditioning task and tested it in six healthy volunteers, followed by male DMD (n = 11) and Control (n = 9) participants aged 7-12 years. The aims of this methodological task development study were to: i) confirm the task efficacy; ii) optimise data processing procedures; iii) determine the most appropriate outcome measures. In the task, two neutral visual stimuli were presented: one 'safe' cue presented alone; one 'threat' cue paired with a threat stimulus (aversive noise) to enable conditioning of physiological startle responses (skin conductance response, SCR, and heart rate). Outcomes were the unconditioned physiological startle responses to the initial threat, and retention of conditioned responses in the absence of the threat stimulus. We present the protocol development and optimisation of data processing methods based on empirical data. We found that the task was effective in producing significantly higher physiological startle SCR in reinforced 'threat' trials compared to 'safe' trials (P < .001). Different data extraction methods were compared and optimised, and the optimal sampling window was derived empirically. SCR amplitude was the most effective physiological outcome measure when compared to SCR area and change in heart rate, with the best profile on data processing, the least variance, successful conditioned response retention (P = .01) and reliability assessment in test-retest analysis (rho = .86). The definition of this novel outcome will allow us to study this response in a DMD population.
Topics: Animals; Child; Conditioning, Classical; Dystrophin; Humans; Male; Mice; Muscular Dystrophy, Duchenne; Reflex, Startle; Reproducibility of Results
PubMed: 35439255
DOI: 10.1371/journal.pone.0264091