Startle habituation, sensory, and sensorimotor gating in trauma-affected refugees with posttraumatic stress disorder

Meteran, Hanieh; Vindbjerg, Erik; Uldall, Sigurd Wiingaard; Glenthøj, Birte; Carlsson, Jessica; Oranje, Bob

doi:10.1017/s003329171800123x

Cited by 19 publications

(14 citation statements)

References 63 publications

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“…The result is an intriguing but sketchy outline of the habituation network, and in the absence of a whole-brain cellular-resolution analysis, numerous questions about this behaviorally important process remain unanswered.Addressing these questions is especially important because of the role that sensorimotor transformations and habituation play in psychiatric disorders including schizophrenia, autism spectrum disorder (ASD), and Fragile X syndrome (FXS) 38 . While these disorders are traditionally diagnosed around their social or cognitive symptoms, each has characteristic alterations in sensory processing, habituation, and sensorimotor gating that compound, or in some cases may drive, social and intellectual impairments 39,40 . FXS patients, for example, show slow habituation 41-44 , a phenotype also found in fmr1-mutant mice that model FXS 45 .…”

mentioning

confidence: 99%

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

Márquez-Legorreta

Constantin

Piber

et al. 2019

Preprint

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Habituation is a form of learning during which animals stop responding to repetitive stimuli, and deficits in habituation are characteristics of several psychiatric disorders. Due to the technical challenges of measuring brain activity comprehensively and at cellular resolution, the brain-wide networks mediating habituation are poorly understood. Here we report brainwide calcium imaging during visual learning in larval zebrafish as they habituate to repeated threatening loom stimuli. We show that different functional categories of loom-sensitive neurons are located in characteristic locations throughout the brain, and that both the functional properties of their networks and the resulting behavior can be modulated by stimulus saliency and timing. Using graph theory, we identify a principally visual circuit that habituates minimally, a moderately habituating midbrain population proposed to mediate the sensorimotor transformation, and downstream circuit elements responsible for higher order representations and the delivery of behavior. Zebrafish larvae carrying a mutation in the fmr1 gene have a systematic shift towards sustained premotor activity in this network, and show slower behavioral habituation. This represents the first description of a visual learning network across the brain at cellular resolution, and provides insights into the circuit-level changes that may occur in people with Fragile X syndrome and related psychiatric conditions.Habituation is a simple form of non-associative learning, characterized by a decrease in response after multiple presentations of a stimulus, that is conserved across much of the animal kingdom 1 . It allows animals to remain attentive to novel and ecologically relevant stimuli while minimizing their expenditure of energy on inputs that occur frequently without consequence. The strength and speed of habituation, and of recovery during periods without the stimulus, depend on the parameters of the stimulus and its repetitions (the intensity, frequency, and number of stimuli) 2,3 . Careful modulations of these stimulus properties have proven useful in exploring the relationships between repetitive stimuli and behavior, thereby providing clues about the underlying habituation circuitry 4-7 .Other work has addressed some of the molecular and cellular dynamics mediating habituation, including reductions in motor neurons' presynaptic vesicle release during shortterm habituation and processes involving protein syntheses for longer-term forms of habituation [8][9][10][11][12][13] . At the other end of the spectrum, fMRI studies in humans have revealed changes in activity for various brain regions during habituation [14][15][16] . The intervening scales, of regional circuits and brain-wide networks, cannot be addressed using targeted cellular techniques or traditional brain-wide approaches. These networks, and the ways in which they change during habituation, can only be addressed by observing activity in whole populations of neurons (up to and including the whole brain) at single-cell...

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mentioning

confidence: 99%

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

Márquez-Legorreta

Constantin

Piber

et al. 2019

Preprint

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“…The sensory overload resulting from reduced sensorimotor gating is thought to give rise to cognitive fragmentation, attentional deficits, and some of the complex clinical symptoms associated with these disorders (Giakoumaki et al, 2008). PPI deficits not only are observed in schizophrenia (Braff et al, 1978) and tic disorders, including Tourette syndrome, but also in patients with a variety of other neuropsychiatric disorders (Table 2), such as ADHD (Ornitz et al, 1992), OCD (Swerdlow et al, 1993), Huntington disease (Swerdlow et al, 1995), premenstrual dysphoric disorder (Kask et al, 2008), post-traumatic stress disorder (Pineles et al, 2016;Meteran et al, 2019), panic disorder (Ludewig et al, 2002), nocturnal enuresis (Freitag et al, 2006), mania in bipolar disorder (Giakoumaki et al, 2007), and autism spectrum disorder (Cheng et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…PPI test (human) PPI deficits in patients with premenstrual dysphoric disorder (Kask et al, 2008). PPI deficits in women with PTSD (Pineles et al, 2016) and in trauma-affected refugees with PTSD (Meteran et al, 2019). Gene association GABRA6 rs3219151 T carriers had greater responses to stress (Uhart et al, 2004;Lynch et al, 2015).…”

Section: Mri (Adult Ptsd)mentioning

confidence: 99%

α6-Containing GABA_AReceptors: Functional Roles and Therapeutic Potentials

et al. 2022

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“…It thus appears that the anti‐PTSD and antidepressant efficacy of TEAS observed in the present study may be related to its broad modulation of multiple neurobiological systems. In addition, sensorimotor gating abnormalities have been suggested in the pathophysiology of PTSD . One study showed that CBT ameliorated impaired sensorimotor gating in patients with psychosis .…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous electrical acupoint stimulation for post‐traumatic stress disorder: Assessor‐blinded, randomized controlled study

Feng

Zhang

Wu³

et al. 2019

Psychiatry Clin Neurosci

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Aim Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post‐traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti‐PTSD efficacy. Methods In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician‐Administered PTSD Scale, PTSD Check List‐Civilian Version, and 17‐item Hamilton Rating Scale for Depression. Results While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post‐baseline measurement points, with moderate to very large effect sizes of 0.484–2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P < 0.001) and on remission (15.0% and 25.0% vs 3.3% and 1.7%, P < 0.001). The incidence of adverse events was similar between groups A and D and between groups B and C. Conclusions Additional TEAS augments the anti‐PTSD and antidepressant efficacy of antidepressants or CBT, without increasing the incidence of adverse effects. TEAS could serve as an effective intervention for PTSD and comorbid depression. This trial was registered with http://www.chictr.org (no.: ChiCTR1800017255).

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Startle habituation, sensory, and sensorimotor gating in trauma-affected refugees with posttraumatic stress disorder

Cited by 19 publications

References 63 publications

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

α6-Containing GABA_AReceptors: Functional Roles and Therapeutic Potentials

Transcutaneous electrical acupoint stimulation for post‐traumatic stress disorder: Assessor‐blinded, randomized controlled study

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Startle habituation, sensory, and sensorimotor gating in trauma-affected refugees with posttraumatic stress disorder

Cited by 19 publications

References 63 publications

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

α6-Containing GABAAReceptors: Functional Roles and Therapeutic Potentials

Transcutaneous electrical acupoint stimulation for post‐traumatic stress disorder: Assessor‐blinded, randomized controlled study

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Product

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α6-Containing GABA_AReceptors: Functional Roles and Therapeutic Potentials