John F. Burke

Direct recordings of grid-like neuronal activity in human spatial navigation

Grid cells in the entorhinal cortex appear to represent spatial location via a triangular coordinate system. Such cells, which have been identified in rats, bats and monkeys, are believed to support a wide range of spatial behaviors. Recording neuronal activity from neurosurgical patients performing a virtual-navigation task, we identified cells exhibiting grid-like spiking patterns in the human brain, suggesting that humans and simpler animals rely on homologous spatial-coding schemes.

Synchronous and asynchronous theta and gamma activity during episodic memory formation.

To test the hypothesis that neural oscillations synchronize to mediate memory encoding, we analyzed electrocorticographic recordings taken as 68 human neurosurgical patients studied and subsequently recalled lists of common words. To the extent that changes in spectral power reflect synchronous oscillations, we would expect those power changes to be accompanied by increases in phase synchrony between the region of interest and neighboring brain areas. Contrary to the hypothesized role of synchronous gamma oscillations in memory formation, we found that many key regions that showed power increases during successful memory encoding also exhibited decreases in global synchrony. Similarly, cortical theta activity that decreases during memory encoding exhibits both increased and decreased global synchrony depending on region and stage of encoding. We suggest that network synchrony analyses, as used here, can help to distinguish between two major types of spectral modulations: (1) those that reflect synchronous engagement of regional neurons with neighboring brain areas, and (2) those that reflect either asynchronous modulations of neural activity or local synchrony accompanied by global disengagement from neighboring regions. We show that these two kinds of spectral modulations have distinct spatiotemporal profiles during memory encoding.

Slow-Theta-to-Gamma Phase–Amplitude Coupling in Human Hippocampus Supports the Formation of New Episodic Memories

Phase-amplitude coupling (PAC) has been proposed as a neural mechanism for coordinating information processing across brain regions. Here we sought to characterize PAC in the human hippocampus, and in temporal and frontal cortices, during the formation of new episodic memories. Intracranial recordings taken as 56 neurosurgical patients studied and recalled lists of words revealed significant hippocampal PAC, with slow-theta activity (2.5-5 Hz) modulating gamma band activity (34-130 Hz). Furthermore, a significant number of hippocampal electrodes exhibited greater PAC during successful than unsuccessful encoding, with the gamma activity at these sites coupled to the trough of the slow-theta oscillation. These same conditions facilitate LTP in animal models, providing a possible mechanism of action for this effect in human memory. Uniquely in the hippocampus, phase preference during item encoding exhibited a biphasic pattern. Overall, our findings help translate between the patterns identified during basic memory tasks in animals and those present during complex human memory encoding. We discuss the unique properties of human hippocampal PAC and how our findings relate to influential theories of information processing based on theta-gamma interactions.

Human intracranial high-frequency activity maps episodic memory formation in space and time.

Noninvasive neuroimaging studies have revealed a network of brain regions that activate during human memory encoding; however, the relative timing of such activations remains unknown. Here we used intracranially recorded high-frequency activity (HFA) to first identify regions that activate during successful encoding. Then, we leveraged the high-temporal precision of HFA to investigate the timing of such activations. We found that memory encoding invokes two spatiotemporally distinct activations: early increases in HFA that involve the ventral visual pathway as well as the medial temporal lobe and late increases in HFA that involve the left inferior frontal gyrus, left posterior parietal cortex, and left ventrolateral temporal cortex. We speculate that these activations reflect higher-order visual processing and top-down modulation of attention/semantic information, respectively.

Subsequent memory effect in intracranial and scalp EEG

Successful memory encoding is marked by increases in 30-100Hz gamma-band activity in a broad network of brain regions. Activity in the 3-8Hz theta band has also been shown to modulate memory encoding, but this effect has been found to vary in direction across studies. Because of the diversity in memory tasks, and in recording and data-analytic methods, our knowledge of the theta frequency modulations remains limited. The difference in the directionality of these theta effects could arise from a distinction between global cortical and deeper subcortical effects. To address this issue, we examined the spectral correlates of successful memory encoding using intracranial EEG recordings in neurosurgical patients and scalp EEG recordings in healthy controls. We found significant theta (3-8Hz) power modulations (both increases and decreases) and high gamma (44-100Hz) power increases in both samples of participants. These results suggest that (1) there are two separate theta mechanisms supporting memory success, a broad theta decrease present across both the cortex and hippocampus as well as a theta power increase in the frontal cortex, (2) scalp EEG is capable of resolving high frequency gamma activity, and (3) iEEG theta effects are likely not the result of epileptic pathology.

Theta and High-Frequency Activity Mark Spontaneous Recall of Episodic Memories

Humans possess the remarkable ability to search their memory, allowing specific past episodes to be re-experienced spontaneously. Here, we administered a free recall test to 114 neurosurgical patients and used intracranial theta and high-frequency activity (HFA) to identify the spatiotemporal pattern of neural activity underlying spontaneous episodic retrieval. We found that retrieval evolved in three electrophysiological stages composed of: (1) early theta oscillations in the right temporal cortex, (2) increased HFA in the left hemisphere including the medial temporal lobe (MTL), left inferior frontal gyrus, as well as the ventrolateral temporal cortex, and (3) motor/language activation during vocalization of the retrieved item. Of these responses, increased HFA in the left MTL predicted recall performance. These results suggest that spontaneous recall of verbal episodic memories involves a spatiotemporal pattern of spectral changes across the brain; however, high-frequency activity in the left MTL represents a final common pathway of episodic retrieval.

Direct Brain Stimulation Modulates Encoding States and Memory Performance in Humans

People often forget information because they fail to effectively encode it. Here, we test the hypothesis that targeted electrical stimulation can modulate neural encoding states and subsequent memory outcomes. Using recordings from neurosurgical epilepsy patients with intracranially implanted electrodes, we trained multivariate classifiers to discriminate spectral activity during learning that predicted remembering from forgetting, then decoded neural activity in later sessions in which we applied stimulation during learning. Stimulation increased encoding-state estimates and recall if delivered when the classifier indicated low encoding efficiency but had the reverse effect if stimulation was delivered when the classifier indicated high encoding efficiency. Higher encoding-state estimates from stimulation were associated with greater evidence of neural activity linked to contextual memory encoding. In identifying the conditions under which stimulation modulates memory, the data suggest strategies for therapeutically treating memory dysfunction.

Decreases in theta and increases in high frequency activity underlie associative memory encoding

Episodic memory encoding refers to the cognitive process by which items and their associated contexts are stored in memory. To investigate changes directly attributed to the formation of explicit associations, we examined oscillatory power captured through intracranial electroencephalography (iEEG) as 27 neurosurgical patients receiving subdural and depth electrodes for seizure monitoring participated in a paired associates memory task. We examined low (3-8Hz) and high (45-95Hz) frequency activity, and found that the successful formation of new associations was accompanied by broad decreases in low frequency activity and a posterior to anterior progression of increases in high frequency activity in the left hemisphere. These data suggest that the observed patterns of activity may reflect the neural mechanisms underlying the formation of novel item-item associations.

Human intracranial high-frequency activity during memory processing: neural oscillations or stochastic volatility?

Intracranial high-frequency activity (HFA), which refers to fast fluctuations in electrophysiological recordings, increases during memory processing. Two views have emerged to explain this effect: (1) HFA reflects a synchronous signal, related to underlying gamma oscillations, that plays a mechanistic role in human memory and (2) HFA reflects an asynchronous signal that is a non-specific marker of brain activation. We review recent data supporting each of these views and conclude that HFA during memory processing is more consistent with an asynchronous signal. Memory-related HFA is therefore best conceptualized as a biomarker of neural activation that can functionally map memory with high spatial and temporal precision.

Prestimulus theta in the human hippocampus predicts subsequent recognition but not recall

Human theta (4−8 Hz) activity in the medial temporal lobe correlates with memory formation; however, the precise role that theta plays in the memory system remains elusive (Hanslmayr and Staudigl, ). Recently, prestimulus theta activity has been associated with successful memory formation, although its specific cognitive role remains unknown (e.g., Fell et al., 2011). In this report, we demonstrate that prestimulus theta in the hippocampus indexes encoding that supports old‐new recognition memory but not recall. These findings suggest that human hippocampal prestimulus theta may preferentially participate in the encoding of item information, as opposed to associative information.