Andrew J. Watrous

Frequency-specific network connectivity increases underlie accurate spatiotemporal memory retrieval

The medial temporal lobes, prefrontal cortex and parts of parietal cortex form the neural underpinnings of episodic memory, which includes remembering both where and when an event occurred. However, the manner in which these three regions interact during retrieval of spatial and temporal context remains untested. We employed simultaneous electrocorticographical recordings across multilobular regions in patients undergoing seizure monitoring while they retrieved spatial and temporal context associated with an episode, and we used phase synchronization as a measure of network connectivity. Successful memory retrieval was characterized by greater global connectivity compared with incorrect retrieval, with the medial temporal lobe acting as a hub for these interactions. Spatial versus temporal context retrieval resulted in prominent differences in both the spectral and temporal patterns of network interactions. These results emphasize dynamic network interactions as being central to episodic memory retrieval, providing insight into how multiple contexts underlying a single event can be recreated in the same network.

Modafinil Shifts Human Locus Coeruleus to Low-Tonic, High-Phasic Activity During Functional MRI

Models of cognitive control posit a key modulatory role for the pontine locus coeruleus–norepinephrine (LC-NE) system. In nonhuman primates, phasic LC-NE activity confers adaptive adjustments in cortical gain in task-relevant brain networks, and in performance, on a trial-by-trial basis. This model has remained untested in humans. We used the pharmacological agent modafinil to promote low-tonic/high-phasic LC-NE activity in healthy humans performing a cognitive control task during event-related functional magnetic resonance imaging (fMRI). Modafanil administration was associated with decreased task-independent, tonic LC activity, increased task-related LC and prefrontal cortex (PFC) activity, and enhanced LC-PFC functional connectivity. These results confirm in humans the role of the LC-NE system in PFC function and cognitive control and suggest a mechanism for therapeutic action of procognitive noradrenergic agents.

Prestimulus theta activity predicts correct source memory retrieval

Recent evidence indicates that the processing of a stimulus can be influenced by preceding patterns of brain activity. Here we examine whether prestimulus oscillatory brain activity can influence the ability to retrieve episodic memories. Neural activity in the theta-frequency band (4–8 Hz) was enhanced before presentation of test items which elicited accurate recollection of contextual details of the prior study episode (“source retrieval”), relative to trials for which item recognition was successful but source retrieval failed. Poststimulus theta activity was also related to source retrieval, and the magnitude of poststimulus theta was predicted by the magnitude of the prestimulus theta effects. The results suggest that ongoing neural processes occurring before stimulus onset might play a critical role in readying the brain for successful memory retrieval.

Behavioral correlates of human hippocampal delta and theta oscillations during navigation

Previous rodent studies demonstrate movement-related increases in theta oscillations, and recent evidence suggests that multiple navigationally relevant variables are reflected in this activity. Human invasive recordings have revealed movement-related modulations in delta and theta activity, although it is unclear whether additional behavioral variables are responsible for modulating this neural activity during navigation. We tested the role of delta and theta oscillations during navigation by addressing whether spatial-related processing, in addition to speed and task variables, modulates delta and theta activity. Recording from 317 hippocampal intracranial electrodes in 10 patients undergoing seizure monitoring, we observed increasing delta and theta power with increasing virtual speed at significantly more electrodes than would be expected by chance, replicating previous findings in nonhuman mammals. Delta and theta power were more consistently modulated, however, as a function of spatial view, including when subjects looked at stores in the virtual environment both to find a relevant goal or for spatial updating. A significantly larger proportion of electrodes showed view-related effects than speed-related modulations. Although speed, task, and spatial view affected delta and theta activity, individual electrodes were most frequently modulated by only one variable, rather than a combination of variables. These electrodes likely sampled independent delta and theta generators, which reflected movement-related and allocentric processing, respectively. These results extend previous findings in nonhuman mammals and humans, expanding our knowledge of the role of human hippocampal low-frequency oscillations in navigation.

A comparative study of human and rat hippocampal low-frequency oscillations during spatial navigation

Rhythmic oscillations within the 3–12 Hz theta frequency band manifest in the rodent hippocampus during a variety of behaviors and are particularly well characterized during spatial navigation. In contrast, previous studies of rhythmic hippocampal activity in primates under comparable behavioral conditions suggest it may be less apparent and possibly less prevalent, or even absent, compared with the rodent. We compared the relative presence of low‐frequency oscillations in rats and humans during spatial navigation by using an oscillation detection algorithm (“P‐episode” or “BOSC”) to better characterize their presence in microelectrode local field potential (LFP) recordings. This method quantifies the proportion of time the LFP exceeds both a power and cycle duration threshold at each frequency, characterizing the presence of (1) oscillatory activity compared with background noise, (2) the peak frequency of oscillatory activity, and (3) the duration of oscillatory activity. Results demonstrate that both humans and rodents have hippocampal rhythmic fluctuations lasting, on average, 2.75 and 4.3 cycles, respectively. Analyses further suggest that human hippocampal rhythmicity is centered around ∼3 Hz while that of rats is centered around ∼8 Hz. These results establish that low‐frequency rhythms relevant to spatial navigation are present in both the rodent and human hippocampus, albeit with different properties under the behavioral conditions tested.

Multiple interacting brain areas underlie successful spatiotemporal memory retrieval in humans

Emerging evidence suggests that our memories for recent events depend on a dynamic interplay between multiple cortical brain regions, although previous research has also emphasized a primary role for the hippocampus in episodic memory. One challenge in determining the relative importance of interactions between multiple brain regions versus a specific brain region is a lack of analytic approaches to address this issue. Participants underwent neuroimaging while retrieving the spatial and temporal details of a recently experienced virtual reality environment; we then employed graph theory to analyze functional connectivity patterns across multiple lobes. Dense, large-scale increases in connectivity during successful memory retrieval typified network topology, with individual participant performance correlating positively with overall network density. Within this dense network, the hippocampus, prefrontal cortex, precuneus, and visual cortex served as “hubs” of high connectivity. Spatial and temporal retrieval were characterized by distinct but overlapping “subnetworks” with higher connectivity within posterior and anterior brain areas, respectively. Together, these findings provide new insight into the neural basis of episodic memory, suggesting that the interactions of multiple hubs characterize successful memory retrieval. Furthermore, distinct subnetworks represent components of spatial versus temporal retrieval, with the hippocampus acting as a hub integrating information between these two subnetworks.

Expected reward modulates encoding-related theta activity before an event

Oscillatory brain activity in the theta frequency range (4–8 Hz) before the onset of an event has been shown to affect the likelihood of successfully encoding the event into memory. Recent work has also indicated that frontal theta activity might be modulated by reward, but it is not clear how reward expectancy, anticipatory theta activity, and memory formation might be related. Here, we used scalp electroencephalography (EEG) to assess the relationship between these factors. EEG was recorded from healthy adults while they memorized a series of words. Each word was preceded by a cue that indicated whether a high or low monetary reward would be earned if the word was successfully remembered in a later recognition test. Frontal theta power between the presentation of the reward cue and the onset of a word was predictive of later memory for the word, but only in the high reward condition. No theta differences were observed before word onset following low reward cues. The magnitude of prestimulus encoding-related theta activity in the high reward condition was correlated with the number of high reward words that were later confidently recognized. These findings provide strong evidence for a link between reward expectancy, theta activity, and memory encoding. Theta activity before event onset seems to be especially important for the encoding of motivationally significant stimuli. One possibility is that dopaminergic activity during reward anticipation mediates frontal theta activity related to memory.

The Spectro-Contextual Encoding and Retrieval Theory of Episodic Memory

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or “SCERT”) that provides several testable predictions for future research.

Modafinil augments oscillatory power in middle frequencies during rule selection

Control-related cognitive processes are associated with cortical oscillations and modulated by catecholamine neurotransmitters. It remains unclear how catecholamine systems modulate control-related oscillations. We tested modafinil effects on rule-related 4-30 Hz oscillations, with double-blind, placebo-controlled (within-subjects) testing of 22 healthy adults, using EEG during cognitive control task performance. EEG data underwent time-frequency decomposition with Morlet wavelets to determine power of 4-30 Hz oscillations. Modafinil enhanced oscillatory power associated with high-control rule selection in theta, alpha, and beta ranges, with a frontotemporal topography and minimal effects during rule maintenance. Augmentation of catecholamine signaling enhances middle-frequency cortical oscillatory power associated with rule selection, which may subserve diverse subcomponent processes in proactive cognitive control.