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Simultaneous Eye Tracking and Single-Neuron Recordings in Human Epilepsy Patients

Intracranial recordings from patients with intractable epilepsy provide a unique opportunity to study the activity of individual human neurons during ...

Cedars-Sinai Medical Center

California Institute of Technology

The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding.

Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation.

Neurons in the primate medial temporal lobe (MTL) respond selectively to visual categories such as faces, contributing to how the brain represents stimulus meaning. However, it remains unknown whether MTL neurons continue to encode stimulus meaning when it changes flexibly as a function of variable task demands imposed by goal-directed behavior. While classically associated with long-term memory, recent lesion and neuroimaging studies show that the MTL also contributes critically to the online guidance of goal-directed behaviors such as visual search. Do such tasks modulate responses of neurons in the MTL, and if so, do their responses mirror bottom-up input from visual cortices or do they reflect more abstract goal-directed properties? To answer these questions, we performed concurrent recordings of eye movements and single neurons in the MTL and medial frontal cortex (MFC) in human neurosurgical patients performing a memory-guided visual search task. We identified a distinct population of target-selective neurons in both the MTL and MFC whose response signaled whether the currently fixated stimulus was a target or distractor. This target-selective response was invariant to visual category and predicted whether a target was detected or missed behaviorally during a given fixation. The response latencies, relative to fixation onset, of MFC target-selective neurons preceded those in the MTL by ∼200 ms, suggesting a frontal origin for the target signal. The human MTL thus represents not only fixed stimulus identity, but also task-specified stimulus relevance due to top-down goal relevance.

Encoding of Target Detection during Visual Search by Single Neurons in the Human Brain.

Deciphering the mechanisms of declarative memory is a major goal of neuroscience. While much theoretical progress has been made, it has proven difficult to experimentally verify key predictions of some foundational models of memory. Recently, single-neuron recordings in human patients have started to provide direct experimental verification of some theories, including mnemonic evidence accumulation, balance-of-evidence for confidence judgments, sparse coding, contextual reinstatement, and the ventral tegmental area (VTA)-hippocampus loop model. Here, we summarize the cell types that have been described in the medial temporal lobe and posterior parietal cortex, discuss their properties, and reflect on how these findings inform theoretical work. This body of work exemplifies the scientific power of a synergistic combination of modeling and human single-neuron recordings to advance cognitive neuroscience.

Ueli Rutishauser

Departments of Neurosurgery and Neurology,
Center for Neural Science and Medicine,
Department of Biomedical Sciences,
Center for Neural Science and Medicine, Department of Biomedical Sciences

Cedars-Sinai Medical Center

Simultaneous Eye Tracking and Single-Neuron Recordings in Human Epilepsy Patients

Ueli Rutishauser

Departments of Neurosurgery and Neurology,Center for Neural Science and Medicine,Department of Biomedical Sciences,Center for Neural Science and Medicine, Department of Biomedical Sciences

Cedars-Sinai Medical Center

Simultaneous Eye Tracking and Single-Neuron Recordings in Human Epilepsy Patients

Departments of Neurosurgery and Neurology,
Center for Neural Science and Medicine,
Department of Biomedical Sciences,
Center for Neural Science and Medicine, Department of Biomedical Sciences