Pattern differentiation and tuning shift in human sensory cortex underlie long-term threat memory

You, Yuqi; Novak, Lucas R.; Clancy, Kevin J.; Li, Wen

doi:10.1016/j.cub.2022.02.076

Cited by 18 publications

(32 citation statements)

References 77 publications

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“…The past decade has seen a rapid expansion of this literature. fMRI studies of threat conditioning not only corroborated earlier findings in the visual and olfactory cortex [29][30][31] but also extended them to the basic auditory cortex [32][33][34]. Meanwhile, fMRI research has also demonstrated encoding of threat from complex real-world scenes in the basic sensory cortex [35,36].…”

Section: Threat Evaluation In Human Sensory Cortexsupporting

confidence: 64%

“…In humans, fMRI correlates of threat conditioning have implicated a threat network comprising similar brain areas as those in rodents [55]. Critically, in the human sensory cortex, across all modalities, associative plasticity has been reliably observed using fMRI [27][28][29][30][31][32][33][34] as well as EEG (as reviewed in [37] and more below). Moreover, such plasticity closely resembles that in animal models.…”

Section: Mechanisms Of Threat Evaluation In the Human Sensory Cortexmentioning

confidence: 99%

“…That is, fMRI multivoxel patterns in the basic sensory (visual, auditory, and olfactory) cortex changed for the CS+ [29] or became distinct between the CS+ and CS- [27,30,33,34].…”

Section: Acquired Associative Representation Of Threat In the Sensory...mentioning

confidence: 99%

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Sensing fear: fast and precise threat evaluation in human sensory cortex

Keil

2023

Trends in Cognitive Sciences

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Section: Threat Evaluation In Human Sensory Cortexsupporting

confidence: 64%

Section: Mechanisms Of Threat Evaluation In the Human Sensory Cortexmentioning

confidence: 99%

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Sensing fear: fast and precise threat evaluation in human sensory cortex

Keil

2023

Trends in Cognitive Sciences

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“…Friedl & Keil, 2020; 2021; McTeague, Gruss, & Keil, 2015; Santos-Mayo, de Echegaray, & Moratti, 2022), auditory (e.g. Letzkus et al 2011; Quirk, Armony, & LeDoux, 1997; Wood, Angeloni, Oxman, Clopath, & Geffen, 2022), and olfactory (You, Novak, Clancy, & Li, 2022) cortices, subcortical networks that drive eye movements and/or pupillary responses are implicated here. Another pressing gap in the current classical conditioning literature base concerns individual-level effects of experimental manipulations (Beckers, Krypotos, Boddez, Effting, & Kindt, 2013; Lonsdorf & Merz, 2017).…”

Section: Discussionmentioning

confidence: 98%

Effects of Aversive Classical Conditioning on Pupil Dilation and Microsaccades

Friedl

Keil

2022

Preprint

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Unintentional shifts of gaze and the modulation of pupil size are both highly automated processes that serve to regulate the initial influx of visual information. The present work investigated these mechanisms as they came to differentially respond to initially unthreatening stimuli following aversive conditioning. The classical conditioning experimental paradigm employed simple grating stimuli (Gabor patches) shown individually at various (5) on-screen locations, one of which was paired with a noxious auditory unconditioned stimulus (US). Aversively paired Gabor patches elicited an attenuated initial constriction of the pupil (pupillary light response; PLR) along with more rapid re-dilation compared to otherwise identical but unpaired gratings. Modulation of both the PLR and the rate of re-dilation following conditioning showed pronounced individual differences. Rapid eye movements away from fixation (microsaccades) were suppressed for the aversively associated compared to unassociated stimulus locations at several post-stimulus latencies. Mutual information between pupil dilation and microsaccade rate, meanwhile, did not differ between the aversively associated and unassociated visual on-screen locations. Together, these results suggest that measures of pupil diameter and microsaccade rate supply complementary information on early-stage processes of associative learning through experience.

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“…The neural mechanisms by which rTMS over the mPFC decreases threat-conditioned responses can be manifold. Fear memories are formed and retrieved by an intricate neural network encompassing the amygdala 60 , the cerebellum [61][62][63] , and sensory cortices 40,[64][65][66][67][68][69][70][71][72] . Through the direct or indirect connections of the mPFC with these areas, it might be that the effects of focal manipulations of mPFC activity (i.e., stimulation or inhibition) reflect more complex and dynamic changes in the overall neural network state and/or influence the activity of some of these areas.…”

Section: Discussionmentioning

confidence: 99%

Medial prefrontal cortex stimulation abolishes implicit reactions to threats and prevents the return of fear

Manassero

Concina

Caraig

et al. 2023

Preprint

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Down-regulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive Transcranial Magnetic Stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial PFC (mPFC) on threat memory and generalization. Here we showed that rTMS applied before threat memory retrieval abolishes implicit reactions to learned and novel stimuli in humans. These effects were not due to inhibition of electrodermal reactivity and enduringly persisted one week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, we observed stronger attenuation of defensive responses in subjects stimulated over the mPFC than the dlPFC. Our findings uncover a prefrontal region whose modulation can permanently hamper implicit reactions to learned dangers, representing an advance to long-term deactivating overreactions to threats.

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Pattern differentiation and tuning shift in human sensory cortex underlie long-term threat memory

Cited by 18 publications

References 77 publications

Sensing fear: fast and precise threat evaluation in human sensory cortex

Sensing fear: fast and precise threat evaluation in human sensory cortex

Effects of Aversive Classical Conditioning on Pupil Dilation and Microsaccades

Medial prefrontal cortex stimulation abolishes implicit reactions to threats and prevents the return of fear

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