Overlap between lesion location and our memory circuit predicted continuous memory scores in an independent dataset of stroke lesions 25 and in an independent dataset of lesions from penetrating head trauma 26 (Fig. Here, we apply this technique to lesions disrupting memory.įull size table Damage to circuit predicts memory in independent datasets This technique, termed lesion network mapping, has been successfully applied to hallucinations, delusions, movement disorders, coma, and even criminality 22, 23, 24. By combining lesion locations with a wiring diagram of the human brain termed the human connectome, we can determine whether lesion locations causing similar symptoms fall within a single brain circuit and the hub of this circuit. Recently, new tools have become available that allow us to better address these questions. In fact, the hypothesis that human brain lesions that disrupt memory localize to a single connected brain circuit has never been formally tested. ![]() ![]() These studies highlight important unanswered questions regarding the localization of human memory including whether memory localizes to a brain circuit, which regions should be included in this circuit, and whether some nodes of this circuit are more important than others 21. For example, brain stimulation aimed at improving human memory has been directed at multiple different brain targets, both inside and outside the traditional circuit of Papez 17, 18, 19, 20. The exact location of this circuit has taken on new importance with the increased prevalence of memory disorders such as Alzheimer’s disease 14, 15 and efforts to identify new therapies 16. Neuroimaging studies have also identified a partially overlapping circuit, termed the default mode network, hypothesized to mediate episodic memory 10, 12, 13. Subsequent work with laboratory animals 6, 7, 8 and human neuroimaging 9, 10, 11 further supported these findings, leading to general acceptance that memory (specifically episodic memory) localizes to the circuit of Papez. The best-known example is patient H.M., who suffered severe anterograde amnesia following bilateral medial temporal lobe resections 2, 5. Although initially described as an emotion circuit, it was later noted that lesions to this circuit disrupted episodic memory 2, 3, 4. In 1937 James Papez described a human brain circuit based on gross pathology that included the hippocampus, anterior thalamus, mammillary bodies of the hypothalamus, posterior cingulate, and fornix 1.
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