Prepulse inhibition deficits in women with PTSD

Pineles, Suzanne L.; Blumenthal, Terry D.; Curreri, Andrew J.; Nillni, Yael I.; Putnam, Katherine M.; Resick, Patricia A.; Rasmusson, Ann M.; Orr, Scott P.

doi:10.1111/psyp.12679

Cited by 41 publications

(37 citation statements)

References 48 publications

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“…PTSD may involve atypical sensory processing, including reduced activity in areas of the ventral visual stream (including the ILF) (Adenauer et al, 2011; Mueller-Pfeiffer et al, 2013) and auditory processing abnormalities (Clark et al, 2009; Neylan et al, 1999). Individuals with PTSD demonstrate insufficient suppression of irrelevant sensory stimuli, including abnormal P50 suppression (Neylan et al, 1999) and prepulse inhibition (Pineles et al, 2016). Although speculative, we suggest that compromise of the ILF could be relevant to these sensory filtering abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Disruption of white matter structural integrity and connectivity in posttraumatic stress disorder: A TBSS and tractography study

et al. 2017

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Background Most studies of brain white matter (WM) in posttraumatic stress disorder (PTSD) have focused on combat trauma, and often were confounded by neurological and substance dependence comorbidity. This study used tract-based spatial statistics (TBSS) and probabilistic tractography to characterize WM microstructure in a mixed-sex community sample of PTSD patients exposed to diverse and multiple traumas, and in trauma-exposed normal comparison (TENC) subjects. Methods TBSS compared diffusion measures between 20 adults with DSM-IV PTSD and 17 TENC, using a whole-brain voxel-wise approach. Probabilistic tractography using Freesurfer’s TRACULA was employed to measure diffusion tensor imaging (DTI) metrics within anatomically defined pathways. DTI metrics were compared between groups and correlated with PTSD symptom severity and trauma load. Results Controlling for age, sex, and motion, PTSD subjects had significantly reduced fractional anisotropy (FA) in a left frontal lobe cluster compared with TENC, at p < 0.05, family-wise error corrected. Tractography identified significant group differences in the inferior longitudinal fasciculus (ILF), including lower FA and higher radial diffusivity in PTSD compared with TENC. Within the PTSD group, FA values were not correlated with symptom severity or trauma load. Results remained significant after removing participants using psychotropic medication or those with comorbid major depression. Conclusions PTSD patients had reduced WM integrity in left hemisphere frontal WM and temporal-occipital WM tracts, compared to trauma-exposed controls. Reduced frontal FA is consistent with compromised top-down attentional control and emotion regulation in PTSD, while reduced ILF FA may be related to sensory processing and gating abnormalities in this disorder.

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Section: Discussionmentioning

confidence: 99%

Disruption of white matter structural integrity and connectivity in posttraumatic stress disorder: A TBSS and tractography study

et al. 2017

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“…PPI is a complex phenomenon that depends on many features of the stimulus, and which shows high variability between individual animals. In spite of, or perhaps because of this complexity, PPI could be a useful methodology for generating mechanistic insights into neuropsychiatric disease, as evidenced by the extensive literature linking PPI ratio to schizophrenia [4][5][6][7][8][9] and other disorders [10][11][12][13][14][15][16][17][18][19][20]. As a step toward that goal, our analytical model allows for a deconstruction of the underlying structure of PPI, which in turn enables robust and replicable studies of the neural circuits underlying PPI, and how those circuits vary among individuals in the context of disease.…”

Section: Assumptions and Limitations Of The Modelmentioning

confidence: 99%

“…Prepulse inhibition of the acoustic startle response (PPI) is a reduction in the magnitude of the acoustic startle response when a weak, non-startling sound-the prepulse-precedes an intense, potentially startling, sound [1][2][3]. Changes in PPI have been linked to various neuropsychiatric disorders, such as schizophrenia [4][5][6][7][8][9], obsessive compulsive disorder [10][11][12][13], Tourette's syndrome [14,15], autism-spectrum disorder [16][17][18], and post-traumatic stress disorder [19,20]. As such, PPI has been promoted as a potential biomarker of brain function in the context of disease [21,22].…”

Section: Introductionmentioning

confidence: 99%

Robust and replicable measurement for prepulse inhibition of the acoustic startle response

et al. 2020

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Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral phenomenon studied extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this phenomenon remains uncertain. Here, we deconstruct the phenomenon of PPI and confirm several limitations of the methodology traditionally utilized to describe PPI, including that the underlying startle response has a non-Gaussian distribution, and that the traditional PPI metric changes with different stimuli. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound processing. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared with wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In contrast, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.

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“…PPI is a complex phenomenon which depends on many features of the stimulus and which shows high variability between individual animals. In spite of this complexity, the extensive literature linking PPIratio to schizophrenia [4][5][6][7][8][9] and other disorders [10][11][12][13][14][15][16][17][18][19] suggests that PPI could be a useful methodology for generating mechanistic insights into neuropsychiatric disease. As a step toward that goal, our analytical model allows for a deconstruction of the underlying structure of PPI, which in turn enables robust and replicable studies of the neural circuits underlying PPI and how those circuits vary among individuals in the context of disease.…”

Section: Assumptions and Limitations Of The Modelmentioning

confidence: 99%

“…Prepulse inhibition of the acoustic startle response (PPI) is a reduction in the magnitude of the acoustic startle response when a weak, non-startling sound-the prepulse-precedes an intense, potentially-startling, sound [1][2][3] . Changes in PPI have been linked to various neuropsychiatric disorders, such as schizophrenia [4][5][6][7][8][9] , obsessive compulsive disorder [10][11][12] , Tourette's syndrome 13,14 , autism spectrum disorder [15][16][17] , and posttraumatic stress disorder 18,19 . As such, PPI has been promoted as a potential biomarker of brain function in the context of disease 20,21 .…”

Section: Introductionmentioning

confidence: 99%

Robust and replicable measurement for prepulse inhibition of the acoustic startle response

Miller¹,

Kastner²,

Grzybowski

et al. 2019

Preprint

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Measuring animal behavior in the context of experimental manipulation is critical for modeling and understanding neuro-psychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral paradigm used extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this metric remains uncertain. Here we deconstruct the phenomenon of PPI. We first confirm several limitations of the traditional PPI metric, including that the underlying startle response has a non-Gaussian distribution and that the traditional PPI metric changes with different stimulus condition. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound perception. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared to wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In addition, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.state 41 , habituation 42 , socialization 43,44 , and the baseline startle response 45 . Consequently, there is a pressing need for an approach that could consistently identify real differences among groups. We therefore sought to deconstruct the phenomenon of PPI to develop a more accurate methodology for capturing the way in which a prepulse stimulus modifies the acoustic startle response.The traditional methodology for PPI makes four assumptions: 1) the startle response can be accurately measured with a small number of trials per animal; 2) the startle response has an approximately Gaussian distribution, allowing the use of the mean startle response as the basis of the PPI metric; 3) PPI is stable across startle sound levels, enabling the measurement of PPI at a single startle level instead of necessitating a full measurement of the startle function; and 4) PPI is independent of the baseline startle response, allowing for a direct combination of PPI results between animals.Using data from 72 rats across more than 100 stimulus conditions, for a total of over 300,000 trials, we replicated previous work demonstrating that the aforementioned assumptions do not hold. Specifically, our findings confirm: 1) the startle response is highly variable 46 ; 2) the startle response has a non-Gaussian distribution that is better represented by a log-normal distribution 47 ; 3) the traditional metric used for PPI systematically decreases as a functio...

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Prepulse inhibition deficits in women with PTSD

Cited by 41 publications

References 48 publications

Disruption of white matter structural integrity and connectivity in posttraumatic stress disorder: A TBSS and tractography study

Disruption of white matter structural integrity and connectivity in posttraumatic stress disorder: A TBSS and tractography study

Robust and replicable measurement for prepulse inhibition of the acoustic startle response

Robust and replicable measurement for prepulse inhibition of the acoustic startle response

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