Improved autobiographical memory with central thalamic deep brain stimulation in traumatic brain injury

Memory impairment is a common, debilitating consequence of moderate-to-severe traumatic brain injury, affecting daily life functions. There are few treatment options for memory impairment, particularly for real-life autobiographical memory. Recently, in a first-in-human Phase I clinical trial, we demonstrated the improvement of executive attention and arousal in five participants with moderate-to-severe traumatic brain injury using deep brain stimulation of the central thalamus, specifically the central lateral nucleus and its projecting fibres within the medial portion of the dorsal tegmental tract [Schiff et al. (Thalamic deep brain stimulation in traumatic brain injury: A phase 1, randomized feasibility study. Nat Med 2023; 29: 3162-74.)]. Here in this within-subject study, we report a concomitant improvement in autobiographical memory in all five participants. Participants were tested on their ability to recall autobiographical memories using a cue word-based recall task, and on the specificity of memories using the Autobiographical Interview [Levine et al. (Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychol Aging 2002; 17: 677-89.)], before the start of treatment and at sessions ∼3, 6, 9 or 13 months thereafter. Participants also provided self-reports of autobiographical memory changes during treatment. All five participants showed an increase in the average number of autobiographical memories recalled with treatment (range: 12-100%, average: 45.9%, P = 0.032). Autobiographical Interview testing of the last four participants showed an average increase with treatment in the specificity of the recalled autobiographical memories, as measured by the per cent of episodic (temporally- and spatially-specific to the memory) details out of the total episodic and semantic (factual, not memory-specific) details (18.7% improvement; main effect of treatment time F(3,9) = 5.85, P = 0.017). In subjective self-reports, four of the five participants clearly endorsed autobiographical memory improvements in their daily lives, collectively in the detail and vividness of the memories, the frequency of memories recalled, and the recollection of memories from time periods of post-traumatic retrograde amnesia. These results raise the possibility that the central thalamus modulates the autobiographical memory system, potentially via the glutamatergic connections of the targeted fibres emanating from the central lateral nucleus. The increased recall and specificity of autobiographical memories following treatment suggest that central thalamic deep brain stimulation may work to stabilize and refine the multi-faceted process of autobiographical memory retrieval, resulting in improved memory and, in turn, more effective everyday function. These findings support the possible use of central thalamic deep brain stimulation for improving autobiographical memory in moderate-to-severe traumatic brain injury.