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The Journal of Neuroscience : the... Apr 2017Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite...
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 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. 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.
Topics: Acoustic Stimulation; Animals; Habituation, Psychophysiologic; In Vitro Techniques; Large-Conductance Calcium-Activated Potassium Channels; Male; Neuroimaging; Neuronal Plasticity; Patch-Clamp Techniques; Phosphorylation; Pons; Rats; Reflex, Startle; Synapses; Voltage-Sensitive Dye Imaging
PubMed: 28348135
DOI: 10.1523/JNEUROSCI.3699-16.2017 -
PloS One 2018There is a significant need to develop objective measures for identifying children under the age of 8 who have anxiety and depression. If left untreated, early...
There is a significant need to develop objective measures for identifying children under the age of 8 who have anxiety and depression. If left untreated, early internalizing symptoms can lead to adolescent and adult internalizing disorders as well as comorbidity which can yield significant health problems later in life including increased risk for suicide. To this end, we propose the use of an instrumented fear induction task for identifying children with internalizing disorders, and demonstrate its efficacy in a sample of 63 children between the ages of 3 and 7. In so doing, we extract objective measures that capture the full six degree-of-freedom movement of a child using data from a belt-worn inertial measurement unit (IMU) and relate them to behavioral fear codes, parent-reported child symptoms and clinician-rated child internalizing diagnoses. We find that IMU motion data, but not behavioral codes, are associated with parent-reported child symptoms and clinician-reported child internalizing diagnosis in this sample. These results demonstrate that IMU motion data are sensitive to behaviors indicative of child psychopathology. Moreover, the proposed IMU-based approach has increased feasibility of collection and processing compared to behavioral codes, and therefore should be explored further in future studies.
Topics: Accelerometry; Affect; Anxiety Disorders; Child; Child, Preschool; Depressive Disorder; Fear; Female; Humans; Male; Motor Activity; Parents; Physicians; Psychological Tests; Reflex, Startle; Surveys and Questionnaires; Wearable Electronic Devices
PubMed: 29694369
DOI: 10.1371/journal.pone.0195598 -
Frontiers in Neural Circuits 2021Learning declines with age. Recent evidence indicates that the brainstem may play an important role in learning and motor skill acquisition. Our objective was to...
Learning declines with age. Recent evidence indicates that the brainstem may play an important role in learning and motor skill acquisition. Our objective was to determine if delays in the reticular formation, measured via the startle reflex, correspond to age-related deficits in learning and retention. We hypothesized that delays in the startle reflex would be linearly correlated to learning and retention deficits in older adults. To determine if associations were unique to the reticulospinal system, we also evaluated corticospinal contributions with transcranial magnetic stimulation. Our results showed a linear relationship between startle onset latency and percent learning and retention but no relationship between active or passive motor-evoked potential onsets or peak-to-peak amplitude. These results lay the foundation for further study to evaluate if (1) the reticular formation is a subcortical facilitator of skill acquisition and (2) processing delays in the reticular formation contribute to age-related learning deficits.
Topics: Evoked Potentials, Motor; Learning; Reflex, Startle; Reticular Formation; Transcranial Magnetic Stimulation
PubMed: 35153677
DOI: 10.3389/fncir.2021.681706 -
Psychiatry Research Sep 2019Heightened responsivity to unpredictable, and perhaps predictable, threat characterizes some internalizing disorders and may be vulnerability factors for psychopathology...
Heightened responsivity to unpredictable, and perhaps predictable, threat characterizes some internalizing disorders and may be vulnerability factors for psychopathology as well. However, few studies have directly tested whether individual differences in unpredictable and/or predictable threat responding longitudinally predict symptoms of psychopathology and functional outcomes. Examining functioning is particularly important given that functioning is separable from symptoms of psychopathology. The present study examined whether electromyography startle measures of predictable and/or unpredictable threat responding was associated with interviewer-assessed symptoms of internalizing psychopathology and functional impairment at baseline (n = 409) and one-year follow-up (n = 104). Elevated startle responding to unpredictable and predictable threat longitudinally predicted a worsening of functioning over time and this effect was independent of change of symptoms over time. Importantly, threat responding at baseline predicted functional impairment during the follow-up independent of the effects of DSM-defined fear-based (e.g., panic disorder) or distress-misery (e.g., major depressive disorder) internalizing disorders. These findings provide initial support for the incremental validity of neurobiological vulnerability markers of threat responding over and above DSM disorders and highlight the importance of distinguishing functional outcomes from symptom outcomes.
Topics: Adolescent; Adult; Cross-Sectional Studies; Depressive Disorder, Major; Electromyography; Fear; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Panic Disorder; Predictive Value of Tests; Reflex, Startle; Young Adult
PubMed: 30853118
DOI: 10.1016/j.psychres.2019.02.072 -
Behaviour Research and Therapy Jun 2023Recent theoretical and clinical articles have emphasized a role for expectancy violations in improving the effectiveness of exposure therapy. Expectancy violations are...
Recent theoretical and clinical articles have emphasized a role for expectancy violations in improving the effectiveness of exposure therapy. Expectancy violations are critical to extinction learning and strengthening these violations has been suggested to improve the formation and retention of extinction memories, which should result in lasting symptom reductions after treatment. However, more detailed mechanistic insights in this process are needed to better inform clinical interventions. In two separate fear-conditioning experiments, we investigated whether stronger expectancy violations (Exp1) or fostering awareness of expectancy violations (Exp2) during extinction could reduce the subsequent return of fear. We measured fear potentiated startle (FPS) and skin conductance responses (SCR) as physiological indices of fear, and US expectancy ratings to assess our manipulations. While we successfully created stronger expectancy violations in Exp1, we found no evidence that these stronger violations reduced the return of fear at test. Interestingly, fostering awareness of violations (Exp2) reduced differential SCRs, but not FPS responses. These findings provide novel insights into the effect of US expectancies on fear extinction in the lab, but they also illustrate the complexity of capturing clinically relevant processes of change with fear-conditioning studies.
Topics: Humans; Fear; Extinction, Psychological; Conditioning, Classical; Galvanic Skin Response; Reflex, Startle
PubMed: 37087796
DOI: 10.1016/j.brat.2023.104319 -
Psychophysiology Apr 2022Freezing to impending threat is a core defensive response. It has been studied primarily using fear conditioning in non-human animals, thwarting advances in...
Freezing to impending threat is a core defensive response. It has been studied primarily using fear conditioning in non-human animals, thwarting advances in translational human anxiety research that has used other indices, such as skin conductance responses. Here we examine postural freezing as a human conditioning index for translational anxiety research. We employed a mixed cued/contextual fear-conditioning paradigm where one context signals the occurrence of the US upon the presentation of the CS, and another context signals that the CS is not followed by the US. Critically, during the following generalization phase, the CS is presented in a third and novel context. We show that human freezing is highly sensitive to fear conditioning, generalizes to ambiguous contexts, and amplifies with threat imminence. Intriguingly, stronger parasympathetically driven freezing under threat, but not sympathetically mediated skin conductance, predicts subsequent startle magnitude. These results demonstrate that humans show fear-conditioned animal-like freezing responses, known to aid in active preparation for unexpected attack, and that freezing captures real-life anxiety expression. Conditioned freezing offers a promising new, non-invasive, and continuous, readout for human fear conditioning, paving the way for future translational studies into human fear and anxiety.
Topics: Animals; Conditioning, Classical; Fear; Freezing; Generalization, Psychological; Humans; Reflex, Startle
PubMed: 34954858
DOI: 10.1111/psyp.13983 -
Psychiatry Research Nov 2020Changes to the DSM-5's conceptualization of posttraumatic stress disorder (PTSD) highlight the importance of impulsivity within the context of PTSD-related arousal...
Changes to the DSM-5's conceptualization of posttraumatic stress disorder (PTSD) highlight the importance of impulsivity within the context of PTSD-related arousal dysregulation. While the relationship between PTSD and threat sensitivity is well defined, how they relate to impulsivity remains understudied. We examined the relationship between PTSD symptom severity, threat sensitivity, and impulsivity. 124 participants completed the PTSD Checklist (PCL-C) and the Barratt Impulsiveness Scale 11th ed (BIS-11). BIS-11 items were separated to define cognitive and behavioral impulsivity subdomains. A trauma-exposed subsample of 39 participants were also exposed to no, ambiguous, and high threat conditions in a threat-enhanced acoustic startle paradigm with psychophysiological response as the outcome variable. PTSD severity was significantly associated with greater overall impulsivity and behavioral impulsivity. Greater overall impulsivity and both cognitive and behavioral impulsivity subdomains were significantly associated with psychophysiological magnitudes across threat conditions in the traumatized subsample. Our results suggest PTSD severity may linked to behavioral impulsivity and both cognitive and behavioral impulsivity are associated with threat sensitivity and hyperarousal. Assessing impulsivity within the context of PTSD, particularly in terms of its cognitive and behavioral subdomains, may provide important, clinically relevant information.
Topics: Adult; Arousal; Biomarkers; Female; Humans; Impulsive Behavior; Male; Psychophysiology; Reflex, Startle; Severity of Illness Index; Stress Disorders, Post-Traumatic; Tunisia; Young Adult
PubMed: 32977054
DOI: 10.1016/j.psychres.2020.113468 -
Brain and Cognition Feb 2017Although researchers have long hypothesized a relationship between attention and anxiety, theoretical and empirical accounts of this relationship have conflicted. We...
Although researchers have long hypothesized a relationship between attention and anxiety, theoretical and empirical accounts of this relationship have conflicted. We attempted to resolve these conflicts by examining relationships of attentional abilities with responding to predictable and unpredictable threat - related but distinct motivational process implicated in a number of anxiety disorders. Eighty-one individuals completed a behavioral task assessing efficiency of three components of attention - alerting, orienting, and executive control (Attention Network Test - Revised). We also assessed startle responding during anticipation of both predictable, imminent threat (of mild electric shock) and unpredictable contextual threat. Faster alerting and slower disengaging from non-emotional attention cues were related to heightened responding to unpredictable threat, whereas poorer executive control of attention was related to heightened responding to predictable threat. This double dissociation helps to integrate models of attention and anxiety and may be informative for treatment development.
Topics: Adult; Anticipation, Psychological; Anxiety; Attention; Executive Function; Fear; Female; Humans; Male; Reflex, Startle; Young Adult
PubMed: 27816781
DOI: 10.1016/j.bandc.2016.09.012 -
Schizophrenia Research Oct 2020Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed....
BACKGROUND
Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertaken to replicate and extend this solitary finding in a larger cohort.
METHODS
Schizophrenia probands, their relatives, and control subjects from the Consortium on the Genetics of Schizophrenia (COGS-1) were tested in a paradigm to ascertain magnitude, latency, and prepulse inhibition of startle. Trial types in the paradigm were: pulse-alone, and trials with 30, 60, or 120 ms between the prepulse and pulse. Comparisons of subject groups were conducted with ANCOVAs to assess startle latency and magnitude. Heritability of startle magnitude and latency was analyzed with a variance component method implemented in SOLAR v.4.3.1.
RESULTS
980 subjects had analyzable startle results: 199 schizophrenia probands, 456 of their relatives, and 325 controls. A mixed-design ANCOVA on startle latency in the four trial types was significant for subject group (F(2,973) = 4.45, p = 0.012) such that probands were slowest, relatives were intermediate and controls were fastest. Magnitude to pulse-alone trials differed significantly between groups by ANCOVA (F(2,974) = 3.92, p = 0.020) such that controls were lowest, probands highest, and relatives intermediate. Heritability was significant (p < 0.0001), with heritability of 34-41% for latency and 45-59% for magnitude.
CONCLUSION
Both startle latency and magnitude are significantly heritable in the COGS-1 cohort. Startle latency is a strong candidate for being an endophenotype in schizophrenia.
Topics: Acoustic Stimulation; Acoustics; Humans; Prepulse Inhibition; Reflex, Startle; Schizophrenia
PubMed: 33189519
DOI: 10.1016/j.schres.2020.11.003 -
Journal of Neurophysiology Apr 2022Control of limb movements may be impaired after stroke due to the loss of connectivity between the cerebral cortex and spinal cord. A notion to improve motor function in... (Meta-Analysis)
Meta-Analysis Review
Control of limb movements may be impaired after stroke due to the loss of connectivity between the cerebral cortex and spinal cord. A notion to improve motor function in stroke survivors is to use alternate motor fibers, such as the reticulospinal tract (RST), which originate from the brainstem and terminate at different levels of spinal cord. One way of targeting the RST is to use a "StartReact" protocol to foster premature release of a preplanned movement in response to a startling stimulus. Our aim was to find support for the preservation of such StartReact effect in stroke survivors. We conducted a systematic review with meta-analysis of literature published in English up to September 2020, to explore differences in motor responses to startling stimuli in StartReact effects. Protocol of the study was registered (PROSPERO Registration No. CRD42020191581). PubMed, Google Scholar, Web of Science, PsycINFO, and Science Direct were searched for relevant literature. The meta-analysis contained six studies involving a total of 151 stroke and healthy participants. Muscle onset latency data were extracted from the qualifying studies and compared using RevMan. StartReact effect was present in both stroke and healthy groups, represented by shortened muscle onset latency when startling stimulus was present. There was considerable heterogeneity of the outcome measures, which was attributed to the range of motor impairments among stroke survivors and methodologies used. Our findings support the notion of preservation of preprogramming ability and suitability of RST and StartReact effect for motor rehabilitation following stroke.
Topics: Acoustic Stimulation; Electromyography; Humans; Reflex, Startle; Stroke; Stroke Rehabilitation; Survivors
PubMed: 35235444
DOI: 10.1152/jn.00392.2021