Our knowledge of the human brain circuitry that mediates memory formation, and memory enhancement for salient events, largely derives from non-invasive brain imaging studies. However, these lack either the temporal or spatial resolution to characterise the local electrophysiological responses in structures deep in the brain, and how different structures interact to form memories for surprising or emotional events. In RememberEx, we have overcome these limitations be recording from rare patients with electrodes implanted in deep structures. The insights provided by this approach have been striking, ascribing specific electrophysiological mechanisms to detection of unexpected events, processing of unpredictable contexts, and forming memories for emotionally aversive events. Furthermore, we have defined a brain circuit associated with voluntary action-induced memory enhancement, and localised a memory “sweet spot” in the nucleus accumbens where deep brain stimulation leads to memory enhancement, particularly for unexpected stimuli.
In the remainder of the project, we will build on these results to delve deeper into the circuit-level dynamics of memory formation for salient events. Having worked out how the amygdala and hippocampus couple to form emotional memories, we will now study the contribution of a nearby cortical area, the temporal pole, in this process. Rare patients with focal lesions in this area show profound deficits in emotional memory, and ongoing neuropsychological, MRI and electrophysiological studies in these patients will characterise the nature of this deficit and how these lesions may alter activity in distant brain regions. Single unit recordings will be analysed to 1) probe whether dissociable medial temporal responses to low vs high spatial frequency faces are evident at the single neuron level, and 2) determine whether individual neuron(s) show a stereotypical response during sharp wave ripples before and after stimuli presented in an unpredictable context. We will use state of the art magnetoencephalographic recordings in patients undergoing deep brain stimulation to probe how stimulation of the memory “sweet spot” in the nucleus accumbens affects hippocampal responses during encoding of unexpected events. Lastly, intraoperative electrical recordings during deep brain stimulation surgery will provide insights into the responses of the mesolimbic dopamine system during the encoding of unexpected events.
