Emotional Memory Processing during REM Sleep with Implications for Post-Traumatic Stress Disorder

Abstract

REM sleep is important for the processing of emotional memories, including fear memories. Rhythmic interactions, especially in the theta band, between the medial prefrontal cortex (mPFC) and limbic structures are thought to play an important role, but the ways in which memory processing occurs at a mechanistic and circuits level are largely unknown. To investigate how rhythmic interactions lead to fear extinction during REM sleep, we used a biophysically based model that included the infralimbic cortex (IL), a part of the mPFC with a critical role in suppressing fear memories. Theta frequency (4–12 Hz) inputs to a given cell assembly in IL, representing an emotional memory, resulted in the strengthening of connections from the IL to the amygdala and the weakening of connections from the amygdala to the IL, resulting in the suppression of the activity of fear expression cells for the associated memory. Lower frequency (4 Hz) theta inputs effected these changes over a wider range of input strengths. In contrast, inputs at other frequencies were ineffective at causing these synaptic changes and did not suppress fear memories. Under post-traumatic stress disorder (PTSD) REM sleep conditions, rhythmic activity dissipated, and 4 Hz theta inputs to IL were ineffective, but higher-frequency (10 Hz) theta inputs to IL induced changes similar to those seen with 4 Hz inputs under normal REM sleep conditions, resulting in the suppression of fear expression cells. These results suggest why PTSD patients may repeatedly experience the same emotionally charged dreams and suggest potential neuromodulatory therapies for the amelioration of PTSD symptoms.SIGNIFICANCE STATEMENTRhythmic interactions in the theta band between the mPFC and limbic structures are thought to play an important role in processing emotional memories, including fear memories, during REM sleep. The infralimbic cortex (IL) in the mPFC is thought to play a critical role in suppressing fear memories. We show that theta inputs to the IL, unlike other frequency inputs, are effective in producing synaptic changes that suppress the activity of fear expression cells associated with a given memory. Under PTSD REM sleep conditions, lower-frequency (4 Hz) theta inputs to the IL do not suppress the activity of fear expression cells associated with the given memory but, surprisingly, 10 Hz inputs do. These results suggest potential neuromodulatory therapies for PTSD.

Paradoxical kinesia induced by nightmare: unique case report and insights regarding the neural mechanism based on human and rat studies

“…We argue that the frightening nightmare experience might have activated structures belonging to the brain aversive system (BAS) to produce paradoxical kinesia. Indeed, emotional memories, including fear memories, are processed during REM sleep and involve interactions between the amygdala and the infralimbic medial prefrontal cortex in humans [ 9 ]. Patients undergoing stereotaxic neurosurgery reported strong feelings of fear, impending death or non-localized pain suffering caused by electrical stimulation of the inferior colliculus (IC), periaqueductal gray or amygdala [ 10 , 11 ], structures which in humans and non-humans belong to the BAS.…”

Synchronization in a Three Level Network of All-to-All Quasi-Periodically Forced Hodgkin-Huxley Reaction-Diffusion Equations

“…In the context of EEG data driven modeling, recent studies have shown the importance of periodic current sources to retrieve real spatiotemporal signals, see [6,7]. HH neural networks have also been used recently to model the effect of specific frequency stimulation to help patients suffering from Post-Traumatic Stress Disorder (PTSD), see [8].…”