Memory recollections and voluntary actions are often perceived as spontaneously generated irrespective of external stimuli. Although products of our neurons, they are only rarely accessible in humans at the neuronal level. Here I review insights gleaned from unique neurosurgical opportunities to record and stimulate single-neuron activity in people who can declare their thoughts, memories and wishes. I discuss evidence that the subjective experience of human recollection and that of voluntary action arise from the activity of two internal neuronal generators, the former from medial temporal lobe reactivation and the latter from frontoparietal preactivation. I characterize properties of these generators and their interaction, enabling flexible recruitment of memory-based choices for action as well as recruitment of action-based plans for the representation of conceptual knowledge in memories. Both internal generators operate on surprisingly explicit but different neuronal codes, which appear to arise with distinct single-neuron activity, often observed before participants’ reports of conscious awareness. I discuss prediction of behaviour based on these codes, and the potential for their modulation. The prospects of editing human memories and volitions by enhancement, inception or deletion of specific, selected content raise therapeutic possibilities and ethical concerns.
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This work was supported by the the National Institute of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS: grants U01NS108930 and 1R01NS084017 to I.F.) and the National Science Foundation (NSF: grant 1756473 to I.F.).
The author declares no competing interests.
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Fried, I. Neurons as will and representation. Nat Rev Neurosci 23, 104–114 (2022). https://doi.org/10.1038/s41583-021-00543-8