Theta phase precession supports memory formation and retrieval of naturalistic experience in humans.

Associating different aspects of experience with discrete events is critical for human memory. A potential mechanism for linking memory components is phase precession, during which neurons fire progressively earlier in time relative to theta oscillations. However, no direct link between phase precession and memory has been established. Here we recorded single-neuron activity and local field potentials in the human medial temporal lobe while participants (n = 22) encoded and retrieved memories of movie clips. Bouts of theta and phase precession occurred following cognitive boundaries during movie watching and following stimulus onsets during memory retrieval. Phase precession was dynamic, with different neurons exhibiting precession in different task periods. Phase precession strength provided information about memory encoding and retrieval success that was complementary with firing rates. These data provide direct neural evidence for a functional role of phase precession in human episodic memory.

A corollary discharge mediates saccade-related inhibition of single units in mnemonic structures of the human brain.

Despite the critical link between visual exploration and memory, little is known about how neuronal activity in the human mesial temporal lobe (MTL) is modulated by saccades. Here, we characterize saccade-associated neuronal modulations, unit-by-unit, and contrast them to image onset and to occipital lobe neurons. We reveal evidence for a corollary discharge (CD)-like modulatory signal that accompanies saccades, inhibiting/exciting a unique population of broad-/narrow-spiking units, respectively, before and during saccades and with directional selectivity. These findings comport well with the timing, directional nature, and inhibitory circuit implementation of a CD. Additionally, by linking neuronal activity to event-related potentials (ERPs), which are directionally modulated following saccades, we recontextualize the ERP associated with saccades as a proxy for both the strength of inhibition and saccade direction, providing a mechanistic underpinning for the more commonly recorded saccade-related ERP in the human brain.

Volitional control of individual neurons in the human brain.

Brain-machine interfaces allow neuroscientists to causally link specific neural activity patterns to a particular behaviour. Thus, in addition to their current clinical applications, brain-machine interfaces can also be used as a tool to investigate neural mechanisms of learning and plasticity in the brain. Decades of research using such brain-machine interfaces have shown that animals (non-human primates and rodents) can be operantly conditioned to self-regulate neural activity in various motor-related structures of the brain. Here, we ask whether the human brain, a complex interconnected structure of over 80 billion neurons, can learn to control itself at the most elemental scale-a single neuron. We used the unique opportunity to record single units in 11 individuals with epilepsy to explore whether the firing rate of a single (direct) neuron in limbic and other memory-related brain structures can be brought under volitional control. To do this, we developed a visual neurofeedback task in which participants were trained to move a block on a screen by modulating the activity of an arbitrarily selected neuron from their brain. Remarkably, participants were able to volitionally modulate the firing rate of the direct neuron in these previously uninvestigated structures. We found that a subset of participants (learners), were able to improve their performance within a single training session. Successful learning was characterized by (i) highly specific modulation of the direct neuron (demonstrated by significantly increased firing rates and burst frequency); (ii) a simultaneous decorrelation of the activity of the direct neuron from the neighbouring neurons; and (iii) robust phase-locking of the direct neuron to local alpha/beta-frequency oscillations, which may provide some insights in to the potential neural mechanisms that facilitate this type of learning. Volitional control of neuronal activity in mnemonic structures may provide new ways of probing the function and plasticity of human memory without exogenous stimulation. Furthermore, self-regulation of neural activity in these brain regions may provide an avenue for the development of novel neuroprosthetics for the treatment of neurological conditions that are commonly associated with pathological activity in these brain structures, such as medically refractory epilepsy.

Differential Generation of Saccade, Fixation, and Image-Onset Event-Related Potentials in the Human Mesial Temporal Lobe.

Event-related potentials (ERPs) are a commonly used electrophysiological signature for studying mesial temporal lobe (MTL) function during visual memory tasks. The ERPs associated with the onset of visual stimuli (image-onset) and eye movements (saccades and fixations) provide insights into the mechanisms of their generation. We hypothesized that since eye movements and image-onset provide MTL structures with salient visual information, perhaps they both engage similar neural mechanisms. To explore this question, we used intracranial electroencephalographic data from the MTLs of 11 patients with medically refractory epilepsy who participated in a visual search task. We characterized the electrophysiological responses of MTL structures to saccades, fixations, and image-onset. We demonstrated that the image-onset response is an evoked/additive response with a low-frequency power increase. In contrast, ERPs following eye movements appeared to arise from phase resetting of higher frequencies than the image-onset ERP. Intriguingly, this reset was associated with saccade onset and not termination (fixation), suggesting it is likely the MTL response to a corollary discharge, rather than a response to visual stimulation. We discuss the distinct mechanistic underpinnings of these responses which shed light on the underlying neural circuitry involved in visual memory processing.