bioRxiv Science⌕ Search

Biology subjects

Mosher, C.

Publications and source records attributed to Mosher, C..

4 recordsLinked to original sources

Cellular code for mnemonic pattern separation in the human hippocampus is revealed by false memories

Theoretical models propose that pattern separation, a computation thought to be implemented by the hippocampus, allows us to differentiate between familiar and novel items. However, whether pattern separation operates in the human hippocampus remains contested, with no established single-cell correlate. We recorded the single neuron activity of 3506 neurons in the human brain while 97 patients performed a recognition memory task in which novel images similar to previously seen images led to false memories and associated behavioral errors. We identified two kinds of memory selective neurons distributed across the brain: those responding differently to falsely recognized novel and correctly recognized familiar images in a manner compatible with pattern separation, and the other signaling the subject's choice. At the population level, these cells predicted mnemonic ground truth in the hippocampus and the decision in the pre-supplementary motor area, illustrating the progression from mnemonic signals to decisions. Removing pattern separation-signaling cells abolished the continuous memory strength gradient present in the hippocampus, suggesting a role of these cells in separating memories of different strength. These results establish a single cell correlate for mnemonic pattern separation in the human hippocampus and show its behavioral relevance in episodic memory.

neuroscience↗

Microstimulation of the human dopaminergic midbrain causally reshapes value-based decision-making and happiness

Midbrain circuits are thought to govern reward-guided behavior and momentary happiness, yet causal evidence in humans remains scarce. Here, we show that focal microstimulation of the substantia nigra pars compacta alters both decision making and momentary happiness in patients undergoing awake deep-brain stimulation surgery for Parkinsons disease. During a gambling task with interleaved momentary happiness ratings, stimulation delivered at outcome reduced risk-seeking in the loss domain without increasing overall gambling probability. Stimulation improved choice efficiency, guiding behavior toward gambles with higher expected value and thereby increasing cumulative earnings. Computational modeling revealed selective changes in loss processing, with reduced loss weighting and more linear loss utility, while gain processing remained unchanged. In parallel, stimulation did not tonically elevate happiness but selectively amplified outcome-related happiness changes, scaling with decision value and reward prediction errors. These results provide causal evidence that localized perturbation of human midbrain circuits reshapes valuation, choice, and momentary well-being.

neuroscience↗

Stimulus-specific recruitment of human amygdala neurons predicts episodic memory encoding success

Controlling whether a given experience is encoded into long-term memory and thus later remembered is a crucial component of our memory system whose failure is often at the root of memory disorders. One brain area that takes part in controlling which experiences are remembered is the amygdala, but the mechanisms by which it does so remain poorly understood. Here we examined single-neuron activity and local field potentials as human participants performed recognition memory tasks with visual stimuli. Category-selective amygdala neurons exhibited elevated firing rates during encoding of later remembered items versus forgotten items. This subsequent memory effect was restricted to images of the preferred category of a given cell, was stronger and appeared earlier in the amygdala compared to the hippocampus, and did not depend on the valence and arousal of the stimuli. In contrast, category selective cells immediately upstream in the ventral temporal cortex did not exhibit a subsequent memory effect, highlighting specificity to the amygdala. Successful memory formation was accompanied by enhanced spike-field coherence between the activity of category cells in the amygdala and hippocampal field potentials. These findings, replicated in two large independent datasets with two different tasks, demonstrate that recruitment of stimulus-specific amygdala representations predicts episodic memory formation, particularly in the right amygdala. This data suggests category cells in the right amygdala as a cellular target for interventions to treat memory disorders in humans.

neuroscience↗

Hippocampal Theta Phase Precession Supports Memory Formation and Retrieval of Naturalistic Experience in Humans

Linking different experiences together is a key aspect of episodic memory. A potential neural mechanism for linking sequential events over time is phase precession, which causes neurons to fire progressively earlier in time relative to theta-frequency local field potential oscillations. However, no direct link between phase precession and behaviorally assessed memory encoding or retrieval success has been established. We recorded the activity of single neurons and local field potentials in the human medial temporal lobe (MTL) while participants encoded and retrieved memories of movie clips. Transient brief theta bouts and theta phase precession were observed following cognitive boundaries during movie watching as well as following stimulus onset during memory retrieval. Phase precession was dynamic, with different neurons exhibiting phase precession in different task periods. The strength of phase precession provided information about memory encoding and retrieval success that was not available in firing rates, thereby linking the temporal code established by phase precession to behaviorally assessed memory strength. These data reveal phase precession during non spatial memory in humans and provide direct neural evidence for a functional role of phase precession in episodic memory.

neuroscience↗