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Clinical Neurophysiology Practice 2022Myoclonus and other jerky movements form a large heterogeneous group of disorders. Clinical neurophysiology studies can have an important contribution to support... (Review)
Review
Myoclonus and other jerky movements form a large heterogeneous group of disorders. Clinical neurophysiology studies can have an important contribution to support diagnosis but also to gain insight in the pathophysiology of different kind of jerks. This review focuses on myoclonus, tics, startle disorders, restless legs syndrome, and periodic leg movements during sleep. Myoclonus is defined as brief, shock-like movements, and subtypes can be classified based the anatomical origin. Both the clinical phenotype and the neurophysiological tests support this classification: cortical, cortical-subcortical, subcortical/non-segmental, segmental, peripheral, and functional jerks. The most important techniques used are polymyography and the combination of electromyography-electroencephalography focused on jerk-locked back-averaging, cortico-muscular coherence, and the Bereitschaftspotential. Clinically, the differential diagnosis of myoclonus includes tics, and this diagnosis is mainly based on the history with premonitory urges and the ability to suppress the tic. Electrophysiological tests are mainly applied in a research setting and include the Bereitschaftspotential, local field potentials, transcranial magnetic stimulation, and pre-pulse inhibition. Jerks due to a startling stimulus form the group of startle syndromes. This group includes disorders with an exaggerated startle reflex, such as hyperekplexia and stiff person syndrome, but also neuropsychiatric and stimulus-induced disorders. For these disorders polymyography combined with a startling stimulus can be useful to determine the pattern of muscle activation and thus the diagnosis. Assessment of symptoms in restless legs syndrome and periodic leg movements during sleep can be performed with different validated scoring criteria with the help of electromyography.
PubMed: 36324989
DOI: 10.1016/j.cnp.2022.09.003 -
Aging and Disease Jul 2021Reflex seizures (RS) are epileptic events that are objectively and consistently elicited in response to a specific afferent stimulus or by an activity of the patient.... (Review)
Review
Reflex seizures (RS) are epileptic events that are objectively and consistently elicited in response to a specific afferent stimulus or by an activity of the patient. The specific stimulus can be a variety of heterogenous intrinsic or extrinsic factors, ranging from the simple to the complex, such as flashing lights or reading a book. These seizures can take a variety of forms, comprising either general or focal onset, with or without secondary generalization. Reflex epilepsies (RE) are classified as a specific syndrome in which all epileptic seizures are precipitated by sensory stimuli. The few designated RE include idiopathic photosensitive occipital lobe epilepsy, other visual sensitive epilepsies, primary reading epilepsy, and startle epilepsy. RS that occurs within other focal or generalized epilepsy syndromes that are associated with distinct spontaneous seizures are classified by the overarching seizure type. Most patients experience spontaneous seizures along with their provoked events. RS originate from stimulation of functional anatomic networks normally functioning for physiological activities, that overlap or coincide with regions of cortical hyperexcitability. Generalized RS typically occur within the setting of IGEs and should be considered as focal seizures with quick secondary generalization via cortico-cortical or cortico-reticular pathways. In aggregate, activation of a critical neuronal mass, supported and sustained by cortico-subcortical and thalamocortical pathways eventually result in a seizure. Treatment includes antiseizure medication, commonly valproate or levetiracetam, along with lifestyle modifications, and when amenable, surgical intervention. High clinical suspicion and careful history taking must be employed in all epilepsy patients to identify reflex triggers.
PubMed: 34221545
DOI: 10.14336/AD.2021.0216 -
American Journal of Human Genetics Aug 2022ADGRL1 (latrophilin 1), a well-characterized adhesion G protein-coupled receptor, has been implicated in synaptic development, maturation, and activity. However, the...
ADGRL1 (latrophilin 1), a well-characterized adhesion G protein-coupled receptor, has been implicated in synaptic development, maturation, and activity. However, the role of ADGRL1 in human disease has been elusive. Here, we describe ten individuals with variable neurodevelopmental features including developmental delay, intellectual disability, attention deficit hyperactivity and autism spectrum disorders, and epilepsy, all heterozygous for variants in ADGRL1. In vitro, human ADGRL1 variants expressed in neuroblastoma cells showed faulty ligand-induced regulation of intracellular Ca influx, consistent with haploinsufficiency. In vivo, Adgrl1 was knocked out in mice and studied on two genetic backgrounds. On a non-permissive background, mice carrying a heterozygous Adgrl1 null allele exhibited neurological and developmental abnormalities, while homozygous mice were non-viable. On a permissive background, knockout animals were also born at sub-Mendelian ratios, but many Adgrl1 null mice survived gestation and reached adulthood. Adgrl1 mice demonstrated stereotypic behaviors, sexual dysfunction, bimodal extremes of locomotion, augmented startle reflex, and attenuated pre-pulse inhibition, which responded to risperidone. Ex vivo synaptic preparations displayed increased spontaneous exocytosis of dopamine, acetylcholine, and glutamate, but Adgrl1 neurons formed synapses in vitro poorly. Overall, our findings demonstrate that ADGRL1 haploinsufficiency leads to consistent developmental, neurological, and behavioral abnormalities in mice and humans.
Topics: Adult; Animals; Autism Spectrum Disorder; Disease Models, Animal; Haploinsufficiency; Humans; Intellectual Disability; Mice; Mice, Knockout; Neurodevelopmental Disorders; Receptors, G-Protein-Coupled; Receptors, Peptide
PubMed: 35907405
DOI: 10.1016/j.ajhg.2022.06.011 -
Otolaryngologic Clinics of North America Aug 2020Animal models have significantly contributed to understanding the pathophysiology of chronic subjective tinnitus. They are useful because they control etiology, which in... (Review)
Review
Animal models have significantly contributed to understanding the pathophysiology of chronic subjective tinnitus. They are useful because they control etiology, which in humans is heterogeneous; employ random group assignment; and often use methods not permissible in human studies. Animal models can be broadly categorized as either operant or reflexive, based on methodology. Operant methods use variants of established psychophysical procedures to reveal what an animal hears. Reflexive methods do the same using elicited behavior, for example, the acoustic startle reflex. All methods contrast the absence of sound and presence of sound, because tinnitus cannot by definition be perceived as silence.
Topics: Acoustic Stimulation; Animals; Behavior, Animal; Disease Models, Animal; Hearing; Hearing Loss; Humans; Reflex; Reflex, Startle; Reproducibility of Results; Sound; Tinnitus
PubMed: 32327193
DOI: 10.1016/j.otc.2020.03.001 -
Scientific Reports Feb 2021Previous studies have not clearly demonstrated whether motivational tendencies during reward feedback are mainly characterized by appetitive responses to a gain or...
Previous studies have not clearly demonstrated whether motivational tendencies during reward feedback are mainly characterized by appetitive responses to a gain or mainly by aversive consequences of reward omission. In the current study this issue was addressed employing a passive head or tails game and using the startle reflex as an index of the appetitive-aversive continuum. A second aim of the current study was to use startle-reflex modulation as a means to compare the subjective value of monetary rewards of varying magnitude. Startle responses after receiving feedback that a potential reward was won or not won were compared with a baseline condition without a potential gain. Furthermore, startle responses during anticipation of no versus potential gain were compared. Consistent with previous studies, startle-reflex magnitudes were significantly potentiated when participants anticipated a reward compared to no reward, which may reflect anticipatory arousal. Specifically for the largest reward (20-cents) startle magnitudes were potentiated when a reward was at stake but not won, compared to a neutral baseline without potential gain. In contrast, startle was not inhibited relative to baseline when a reward was won. This suggests that startle modulation during feedback is better characterized in terms of potentiation when missing out on reward rather than in terms of inhibition as a result of winning. However, neither of these effects were replicated in a more targeted second experiment. The discrepancy between these experiments may be due to differences in motivation to obtain rewards or differences in task engagement. From these experiments it may be concluded that the nature of the processing of reward feedback and reward cues is very sensitive to experimental parameters and settings. These studies show how apparently modest changes in these parameters and settings may lead to quite different modulations of appetitive/aversive motivation. A future experiment may shed more light on the question whether startle-reflex modulation after feedback is indeed mainly characterized by the aversive consequences of reward omission for relatively large rewards.
PubMed: 33623052
DOI: 10.1038/s41598-021-82902-0 -
Journal of the Association For Research... Apr 2022Cross-modal plasticity occurs when the function of remaining senses is enhanced following deprivation or loss of a sensory modality. Auditory neural responses are...
Cross-modal plasticity occurs when the function of remaining senses is enhanced following deprivation or loss of a sensory modality. Auditory neural responses are enhanced in the auditory cortex, including increased sensitivity and frequency selectivity, following short-term visual deprivation in adult mice (Petrus et al. Neuron 81:664-673, 2014). Whether or not these visual deprivation-induced neural changes translate into improved auditory perception and performance remains unclear. As an initial investigation of the effects of adult visual deprivation on auditory behaviors, CBA/CaJ mice underwent binocular enucleation at 3-4 weeks old and were tested on a battery of learned behavioral tasks, acoustic startle response (ASR), and prepulse inhibition (PPI) tests beginning at least 2 weeks after the enucleation procedure. Auditory brain stem responses (ABRs) were also measured to screen for potential effects of visual deprivation on non-behavioral hearing function. Control and enucleated mice showed similar tone detection sensitivity and frequency discrimination in a conditioned lick suppression test. Both groups showed normal reactivity to sound as measured by ASR in a quiet background. However, when startle-eliciting stimuli were presented in noise, enucleated mice showed decreased ASR amplitude relative to controls. Control and enucleated mice displayed no significant differences in ASR habituation, PPI tests, or ABR thresholds, or wave morphology. Our findings suggest that while adult-onset visual deprivation induces cross-modal plasticity at the synaptic and circuit levels, it does not substantially influence simple auditory behavioral performance.
Topics: Acoustic Stimulation; Animals; Evoked Potentials, Auditory, Brain Stem; Hearing; Mice; Mice, Inbred CBA; Reflex, Startle
PubMed: 35084628
DOI: 10.1007/s10162-022-00835-5 -
Neuropsychiatric Disease and Treatment 2022The startle reflex is considered a primitive physiological reflex, a defense response that occurs in the organism when the body feels sudden danger and uneasiness,... (Review)
Review
The startle reflex is considered a primitive physiological reflex, a defense response that occurs in the organism when the body feels sudden danger and uneasiness, characterized by habituation and sensitization effects, and studies on the startle reflex often deal with pre-pulse inhibition (PPI) and sensorimotor gating. Under physiological conditions, the startle reflex is stable at a certain level, and when the organism is in a pathological state, such as stroke, spinal cord injury, schizophrenia, and other diseases, the reflex undergoes a series of changes, making it closely related to the progress of disease. This paper summarizes the startle reflex in physiological and pathological states by reviewing the databases of PubMed, Web of Science, Cochrane Library, EMBASE, China Biology Medicine, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, Wanfang Data, and identifies and analyzes the startle reflex and excessive startle reaction disorder.
PubMed: 35237036
DOI: 10.2147/NDT.S351667 -
Journal of Neurovirology Oct 2019In 2007, the nosology for HIV-1-associated neurocognitive disorders (HAND) was updated to a primarily neurocognitive disorder. However, currently available diagnostic... (Review)
Review
In 2007, the nosology for HIV-1-associated neurocognitive disorders (HAND) was updated to a primarily neurocognitive disorder. However, currently available diagnostic tools lack the sensitivity and specificity needed for an accurate diagnosis for HAND. Scientists and clinicians, therefore, have been on a quest for an innovative biomarker to diagnose (i.e., diagnostic biomarker) and/or predict (i.e., prognostic biomarker) the progression of HAND in the post-combination antiretroviral therapy (cART) era. The present review examined the utility and challenges of four proposed biomarkers, including neurofilament light (NFL) chain concentration, amyloid (i.e., sAPPα, sAPPβ, amyloid β) and tau proteins (i.e., total tau, phosphorylated tau), resting-state functional magnetic resonance imaging (fMRI), and prepulse inhibition (PPI). Although significant genotypic differences have been observed in NFL chain concentration, sAPPα, sAPPβ, amyloid β, total tau, phosphorylated tau, and resting-state fMRI, inconsistencies and/or assessment limitations (e.g., invasive procedures, lack of disease specificity, cost) challenge their utility as a diagnostic and/or prognostic biomarker for milder forms of neurocognitive impairment (NCI) in the post-cART era. However, critical evaluation of the literature supports the utility of PPI as a powerful diagnostic biomarker with high accuracy (i.e., 86.7-97.1%), sensitivity (i.e., 89.3-100%), and specificity (i.e., 79.5-94.1%). Additionally, the inclusion of multiple CSF and/or plasma markers, rather than a single protein, may provide a more sensitive diagnostic biomarker for HAND; however, a pressing need for additional research remains. Most notably, PPI may serve as a prognostic biomarker for milder forms of NCI, evidenced by its ability to predict later NCI in higher-order cognitive domains with regression coefficients (i.e., r) greater than 0.8. Thus, PPI heralds an opportunity for the development of a brief, noninvasive diagnostic and promising prognostic biomarker for milder forms of NCI in the post-cART era.
Topics: AIDS Dementia Complex; Amyloid beta-Protein Precursor; Animals; Anti-HIV Agents; Biomarkers; Brain; Brain Chemistry; Brain Mapping; Disease Progression; Female; HIV Infections; HIV-1; Humans; Magnetic Resonance Imaging; Male; Neurofilament Proteins; Prepulse Inhibition; Prognosis; Rats; Rats, Transgenic; Reflex, Startle; Sensitivity and Specificity; tau Proteins
PubMed: 30607890
DOI: 10.1007/s13365-018-0705-6 -
Eye (London, England) Jan 2022
Topics: Humans; Ophthalmology; Postoperative Complications; Reflex, Startle; Surgeons
PubMed: 34326498
DOI: 10.1038/s41433-021-01703-x -
Psychophysiology Dec 2022Trace fear conditioning is an important research paradigm to model aversive learning in biological or clinical scenarios, where predictors (conditioned stimuli, CS) and...
Trace fear conditioning is an important research paradigm to model aversive learning in biological or clinical scenarios, where predictors (conditioned stimuli, CS) and aversive outcomes (unconditioned stimuli, US) are separated in time. The optimal measurement of human trace fear conditioning, and in particular of memory retention after consolidation, is currently unclear. We conducted two identical experiments (N = 28, N = 28) with a 15-s trace interval and a recall test 1 week after acquisition, while recording several psychophysiological observables. In a calibration approach, we explored which learning and memory measures distinguished CS+ and CS- in the first experiment and confirmed the most sensitive measures in the second experiment. We found that in the recall test without reinforcement, only fear-potentiated startle but not skin conductance, pupil size, heart period, or respiration amplitude, differentiated CS+ and CS-. During acquisition without startle probes, skin conductance responses and pupil size responses but not heart period or respiration amplitude differentiated CS+ and CS-. As a side finding, there was no evidence for extinction of fear-potentiated startle over 30 trials without reinforcement. These results may be useful to inform future substantive research using human trace fear conditioning protocols.
Topics: Humans; Fear; Conditioning, Classical; Memory; Conditioning, Operant; Learning; Reflex, Startle; Extinction, Psychological
PubMed: 35675529
DOI: 10.1111/psyp.14119