Memory-related processing is the primary driver of human hippocampal theta oscillations.

Decades of work in rodents suggest that movement is a powerful driver of hippocampal low-frequency "theta" oscillations. Puzzlingly, such movement-related theta increases in primates are less sustained and of lower frequency, leading to questions about their functional relevance. Verbal memory encoding and retrieval lead to robust increases in low-frequency oscillations in humans, and one possibility is that memory might be a stronger driver of hippocampal theta oscillations in humans than navigation. Here, neurosurgical patients navigated routes and then immediately mentally simulated the same routes while undergoing intracranial recordings. We found that mentally simulating the same route that was just navigated elicited oscillations that were of greater power, higher frequency, and longer duration than those involving navigation. Our findings suggest that memory is a more potent driver of human hippocampal theta oscillations than navigation, supporting models of internally generated theta oscillations in the human hippocampus.

Machine learning classifiers for electrode selection in the design of closed-loop neuromodulation devices for episodic memory improvement.

Successful neuromodulation approaches to alter episodic memory require closed-loop stimulation predicated on the effective classification of brain states. The practical implementation of such strategies requires prior decisions regarding electrode implantation locations. Using a data-driven approach, we employ support vector machine (SVM) classifiers to identify high-yield brain targets on a large data set of 75 human intracranial electroencephalogram subjects performing the free recall (FR) task. Further, we address whether the conserved brain regions provide effective classification in an alternate (associative) memory paradigm along with FR, as well as testing unsupervised classification methods that may be a useful adjunct to clinical device implementation. Finally, we use random forest models to classify functional brain states, differentiating encoding versus retrieval versus non-memory behavior such as rest and mathematical processing. We then test how regions that exhibit good classification for the likelihood of recall success in the SVM models overlap with regions that differentiate functional brain states in the random forest models. Finally, we lay out how these data may be used in the design of neuromodulation devices.

Distinct neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex.

Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood-oxygen-level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modelling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70-150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30-70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex.Significance Statement:The blood-oxygen-level-dependent (BOLD) signal forms the basis of fMRI but provides only an indirect measure of neural activity. Task-related modulation of BOLD signals are typically equated with changes in gamma-band activity; however, relevant empirical evidence comes largely from the neocortex. We examined neurophysiological correlates of the BOLD signal in the hippocampus, where the differing neural architecture might result in a different relationship between the respective signals. We identified a positive relationship between encoding-related changes in BOLD and gamma-band activity in frontal and parietal cortex. This effect was reversed in the hippocampus, where BOLD and gamma-band effects negatively covaried. These results suggest regional variability in the transfer function between neural activity and the BOLD signal in the hippocampus and neocortex.

Toxic and Essential Trace Element Content of Commonly Administered Pediatric Oral Medications.

OBJECTIVES: The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications. METHODS: Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication's maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral reference dose, permissible or permitted daily exposure, provisional tolerable weekly intake, and tolerable upper intake concentrations. Exposure guidelines utilized for desired effect were adequate intake and recommended dietary allowance. RESULTS: Intake of the maximum recommended daily dose by 6-month-olds for 1 week would not deliver more than the exposure guideline of any of the elements, with the exceptions of chromium in several medications and zinc in the pediatric electrolyte solution, if it was consumed for 1 week. CONCLUSIONS: Consumed alone, these frequently administered pediatric oral medications would not deliver amounts of toxic elements that exceed established exposure guidelines for adverse effects, nor would most significantly contribute to adequate intake of essential elements.