A pilot study of closed-loop neuromodulation for treatment-resistant post-traumatic stress disorder

Gill, Jay; Schneiders, Julia A.; Stangl, Matthias; Aghajan, Zahra M.; Vallejo, Mauricio; Hiller, Sonja; Topalovic, Uros; Inman, Cory S.; Villaroman, Diane; Bari, Ausaf; Adhikari, Avishek; Rao, Vikram R.; Fanselow, Michael S.; Craske, Michelle G.; Krahl, Scott E.; Chen, James W. Y.; Vick, Mandi M.; Hasulak, Nicholas R.; Kao, Jennifer L.; Koek, Ralph J.; Suthana, Nanthia; Langevin, Jean-Philippe

doi:10.1038/s41467-023-38712-1

Cited by 21 publications

(12 citation statements)

References 41 publications

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“…Furthermore, providing a better mechanistic understanding of amygdala-hippocampal communication during encoding, reactivation and retrieval of aversive information – with precise temporal and spectral resolution – can inform the design of novel stimulation protocols that specifically reproduce or disrupt their dynamic communication. These protocols can build on previous evidence that amygdala theta-burst stimulation enhances memory for neutral stimuli 47 , and a recent report that amygdala closed loop neuromodulation reduces symptoms in two PTSD patients 48 .…”

Section: Discussionmentioning

confidence: 96%

Retrieval of human aversive memories involves reactivation of gamma activity patterns in the hippocampus that originate in the amygdala during encoding

Costa,

Pacheco,

Gil-Nagel

et al. 2024

Preprint

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Emotional memories require coordinated activity of the amygdala and hippocampus. Human intracranial recordings have shown that formation of aversive memories involves an amygdala theta-hippocampal gamma phase code. Yet, the mechanisms engaged during translation of aversive experiences into memories and subsequent retrieval remain unclear. Directly recording from human amygdala and hippocampus, here we show that hippocampal gamma activity increases for correctly remembered aversive scenes, while exerting unidirectional oscillatory influence within the theta/beta frequency range on the amygdala for previously seen aversive scenes. Crucially, patterns of amygdala high amplitude gamma activity at encoding are reactivated in the hippocampus, but not amygdala, during both aversive encoding and retrieval. Trial-specific hippocampal gamma patterns showing highest representational similarity with amygdala activity at encoding are replayed in the hippocampus during aversive retrieval. This reactivation process occurs against a background of gamma activity that is otherwise decorrelated between encoding and retrieval. Thus, retrieval of aversive memories is hippocampal-centered, with hippocampal activity patterns apparently entrained by the amygdala during encoding.

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Section: Discussionmentioning

confidence: 96%

Retrieval of human aversive memories involves reactivation of gamma activity patterns in the hippocampus that originate in the amygdala during encoding

Costa,

Pacheco,

Gil-Nagel

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…We think the future is bright because the application of this type of neural/behavioral model may lead to a deeper knowledge and novel lines of treatment for these highly prevalent disorders. As an example, we described the effectiveness of closed-loop neuromodulation for treatment-resistant PTSD (Gill et al, 2023). Both PICT and the National Institue of Mental Health RDoC approach these issues in a similar manner and have similar goals.…”

Section: Discussionmentioning

confidence: 99%

“…In a preliminary study with two patients suffering from treatment-resistant PTSD, we capitalized on these basic neuroscience research findings by implanting electrodes for chronic recording in the amygdala (Gill et al, 2023). The patients were fully ambulatory enabling recording of amygdala activity continuously both at home and in the clinic.…”

Section: The Relationship Between Human Emotional States and Defensiv...mentioning

confidence: 99%

Fear, defense, and emotion: A neuroethological understanding of the negative valence research domain criteria.

Fanselow,

Hoffman

2024

American Psychologist

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We describe the close correspondence between predatory imminence continuum theory (PICT) and the National Institute of Mental Health's Research Domain Criteria (RDoC) for negative valence. RDoC's negative valence constructs relate aversively motivated behavioral reactions to various levels of threat. PICT divides defensive responses into distinct modes that vary along a continuum of the psychological closeness of predatory threat. While there is a close correspondence between PICT modes and negative valence threat constructs, based on PICT, we describe some potential elaborations of RDoC constructs. Both have consonant views of fear and anxiety and provide explicit distinctions between these emotional states, relating them to specific defensive behaviors and functions. We describe recent data that causally implicate human subjective emotional states with amygdala activity, which is also critical for defensive behavior. We conclude that attention to neuroethological views of defense can advance our understanding of the etiology and treatment of anxiety and stress disorders. Public Significance StatementThe National Institute of Mental Health's Research Domain Criteria (RDoC) for negative valence aims to connect clinical observations relevant to anxiety disorders to their underlying biology. RDoC's negative valence constructs relate aversively motivated behavioral reactions to various levels of threat. We describe the correspondence between predatory imminence theory, which divides defensive responses into distinct modes that vary along a continuum of the psychological closeness of predatory threat and RDoC.

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“…The MED can also help extend multimodal motor BCIs to naturalistic setups where task-related events, such as movement onset, must be detected before decoding is possible. In addition to spiking and LFP, the application of MED to other neural modalities such as intracranial EEG or electrocorticography, which have high potential for translation, is also an important future direction [22,74,75,[84][85][86][87][88][89][90][91][92][93][94][95][96]. Finally, the combination of MED with various learning algorithms for neural population modeling and decoding, even in the presence of external input stimuli (e.g.…”

Section: Applications and Future Directionsmentioning

confidence: 99%

Event detection and classification from multimodal time series with application to neural data

Sadras,

Pesaran,

Shanechi

2024

J. Neural Eng.

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Objective: The detection of events in time-series data is a common signal-processing problem. When the data can be modeled as a known template signal with an unknown delay in Gaussian noise, detection of the template signal can be done with a traditional matched filter. However, in many applications, the event of interest is represented in multimodal data consisting of both Gaussian and point-process time series. Neuroscience experiments for example can simultaneously record multimodal neural signals such as local field potentials (LFPs), which can be modeled as Gaussian, and neuronal spikes, which can be modeled as point processes. Currently, no method exists for event detection from such multimodal data, and as such our objective in this work is to develop a method to meet this need. Approach: Here we address this challenge by developing the multimodal event detector (MED) algorithm which simultaneously estimates event times and classes. To do this, we write a multimodal likelihood function for Gaussian and point-process observations and derive the associated maximum likelihood estimator of simultaneous event times and classes. We additionally introduce a cross-modal scaling parameter to account for model mismatch in real datasets. Main results: We validate this method in extensive simulations as well as in a neural spike-LFP dataset recorded from a macaque monkey performing an eye-movement task, where the events of interest are eye movements with unknown times and directions. We show that the MED can successfully detect eye movement onset and classify eye movement direction. Further, the MED successfully combines information across data modalities, with multimodal performance exceeding unimodal performance. Significance: This method can facilitate applications such as the discovery of latent events in multimodal neural population activity and the development of brain-computer interfaces for naturalistic setups without constrained tasks or prior knowledge of event times.

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A pilot study of closed-loop neuromodulation for treatment-resistant post-traumatic stress disorder

Cited by 21 publications

References 41 publications

Retrieval of human aversive memories involves reactivation of gamma activity patterns in the hippocampus that originate in the amygdala during encoding

Retrieval of human aversive memories involves reactivation of gamma activity patterns in the hippocampus that originate in the amygdala during encoding

Fear, defense, and emotion: A neuroethological understanding of the negative valence research domain criteria.

Event detection and classification from multimodal time series with application to neural data

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