Faculty Bibliography

Memories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys' behavior was largely contrast invariant, contrary to the predictions of an RS-inspired decoder, which could not distinguish responses to images that are repeated from those that are of lower contrast. However, the monkeys' behavioral patterns were well predicted by a linearly decodable variant in which the total spike count was corrected for contrast modulation. These results suggest that the IT neural activity pattern that best aligns with single-exposure visual recognition memory behavior is not RS but rather sensory referenced suppression: reductions in IT population response magnitude, corrected for sensory modulation.

Neuronal oscillations route external and internal information across brain regions. In the olfactory system, the two central nodes-the olfactory bulb (OB) and the piriform cortex (PC)-communicate with each other via neural oscillations to shape the olfactory percept. Communication between these nodes have been well characterized in non-human animals but less is known about their role in the human olfactory system. Using a recently developed and validated EEG-based method to extract signals from the OB and PC sources, we show in healthy human participants that there is a bottom-up information flow from the OB to the PC in the beta and gamma frequency bands, while top-down information from the PC to the OB is facilitated by delta and theta oscillations. Importantly, we demonstrate that there was enough information to decipher odor identity above chance from the low gamma in the OB-PC oscillatory circuit as early as 100 ms after odor onset. These data further our understanding of the critical role of bidirectional information flow in human sensory systems to produce perception. However, future studies are needed to determine what specific odor information is extracted and communicated in the information exchange.

Background: A prominent feature of addiction is the tendency to exploit a previously rewarding resource despite its diminishing returns. Such behavior is aptly captured in animal foraging models that have recently been extended to humans. Catecholaminergic systems are thought to underlie such behavior, but a precise empirical account of this is lacking in humans.
Method(s): We recruited 21 treatment-seeking individuals with opioid use disorder (OUD) and 21 socio-demographically matched controls. Participants completed a patch foraging task, during which they made sequential decisions between "harvesting" a depleting source of rewards or incurring a travel cost to harvest a replenished resource. We further acquired high-resolution (<0.7mm in-plane) neuromelanin-sensitive MRI scans, which reliably probes long-term dopamine and norepinephrine function, in a subset (n=27) of participants. Our imaging protocol separately localized dopaminergic nuclei (SN/VTA) and the noradrenergic LC, which have been theoretically linked to foraging behavior and are implicated in addiction.
Result(s): Behaviorally, OUD participants over-harvested more than controls and showed insensitivity to travel times (travel time effect: p=0.79). These group differences held when controlling for age, sex and cognitive variables. Over-harvesting scaled with increased years of opioid use (OUD; r=-0.51, p=0.03). Our imaging analysis revealed a dissociation whereby, across participants, over-harvesting was associated with lower neuromelanin signal contrast in dopaminergic nuclei (SN/VTA, rho=0.40, p=0.04), but not in LC (p=0.55).
Conclusion(s): Our findings suggest that individual differences in foraging behavior are related to interindividual variability in dopaminergic-but not noradrenergic-circuit function that informs reward rates in dynamic decision environments and may serve as a marker for maladaptive reward-seeking behavior. Supported By: Busch Biomedical Research Grant Keywords: Addiction, Foraging, Dopamine, Neuromelanin-Sensitive MRI
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During the development of the vertebrate nervous systems, genetic programs assemble an immature circuit that is subsequently refined by neuronal activity evoked by external stimuli. However, prior to sensory experience, the intrinsic property of the developing nervous system also triggers correlated network-level neuronal activity, with retinal waves in the developing vertebrate retina being the best documented example. Spontaneous activity has also been found in the visual system of Drosophila Here, we compare the spontaneous activity of the developing visual system between mammalian and Drosophila and suggest that Drosophila is an emerging model for mechanistic and functional studies of correlated spontaneous activity.

STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) prevalence increases with age, but whether OSA-related sleep disruption could interrupt the processing of previously encoded wake information thought to normally occur during sleep in cognitively normal older adults remains unknown. METHODS:Fifty-two older (age = 66.9 ± 7.7 years, 56 % female), community-dwelling, cognitively normal adults explored a 3D maze environment and then performed 3 timed trials before (evening) and after (morning) sleep recorded with polysomnography (PSG) with a 20-minute morning psychomotor vigilance test (PVT). RESULTS:Twenty-two (22) subjects had untreated OSA (Apnea Hypopnea Index (AHI4%) ≥ 5/hour) where severity was mild on average [median (interquartile range (IQR))] AHI4% = 11.0 (20.7)/hour) and 30 subjects had an AHI4% < 5/hour. No significant differences were observed in overnight percent change in completion time or in the pattern of evening pre-sleep maze performance. However, during the morning post-sleep trials, there was a significant interaction between OSA group and morning trial number such that participants with OSA performed worse on average with each subsequent morning trial, whereas those without OSA showed improvements. There were no significant differences in morning PVT performance suggesting that vigilance is unlikely to account for this difference in morning maze performance. Increasing relative frontal slow wave activity (SWA) was associated with better overnight maze performance improvement in participants with OSA (r= 0.51, p = 0.02) but not in those without OSA, and no differences in slow wave activity were observed between groups. CONCLUSIONS:OSA alters morning performance in spatial navigation independent of a deleterious effect on morning vigilance or evening navigation performance. Relative frontal slow wave activity is associated with overnight performance change in older subjects with OSA, but not those without.

Pain is a complex, multidimensional experience that involves dynamic interactions between sensory-discriminative and affective-emotional processes. Pain experiences have a high degree of variability depending on their context and prior anticipation. Viewing pain perception as a perceptual inference problem, we propose a predictive coding paradigm to characterize evoked and non-evoked pain. We record the local field potentials (LFPs) from the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC) of freely behaving rats-two regions known to encode the sensory-discriminative and affective-emotional aspects of pain, respectively. We further use predictive coding to investigate the temporal coordination of oscillatory activity between the S1 and ACC. Specifically, we develop a phenomenological predictive coding model to describe the macroscopic dynamics of bottom-up and top-down activity. Supported by recent experimental data, we also develop a biophysical neural mass model to describe the mesoscopic neural dynamics in the S1 and ACC populations, in both naive and chronic pain-treated animals. Our proposed predictive coding models not only replicate important experimental findings, but also provide new prediction about the impact of the model parameters on the physiological or behavioral read-out-thereby yielding mechanistic insight into the uncertainty of expectation, placebo or nocebo effect, and chronic pain.

Glutamatergic hilar mossy cells (MCs) have axons that terminate both near and far from their cell body but stay within the DG, making synapses primarily in the molecular layer. The long-range axons are considered the primary projection, and extend throughout the DG ipsilateral to the soma, and project to the contralateral DG. The specificity of MC axons for the inner molecular layer (IML) has been considered to be a key characteristic of the DG. In the present study, we made the surprising finding that dorsal MC axons are an exception to this rule. We used two mouse lines that allow for Cre-dependent viral labeling of MCs and their axons: dopamine receptor D2 (Drd2-Cre) and calcitonin receptor-like receptor (Crlr-Cre). A single viral injection into the dorsal DG to label dorsal MCs resulted in labeling of MC axons in both the IML and middle molecular layer (MML). Interestingly, this broad termination of dorsal MC axons occurred throughout the septotemporal DG. In contrast, long-range axons of ventral MCs terminated in the IML, consistent with the literature. Taken together, these results suggest that dorsal and ventral MCs differ significantly in their axonal projections. Since MC projections in the ML are thought to terminate primarily on GCs, the results suggest a dorsal-ventral difference in MC activation of GCs. The surprising difference in dorsal and ventral MC projections should therefore be considered when evaluating dorsal-ventral differences in DG function.

INTRODUCTION/BACKGROUND:The term "lactic acidosis" reinforces the misconception that lactate contributes to acidemia. Although it is common to discover an anion gap acidosis with a concomitant elevated lactate concentration, the two are not mutually dependent. CASE REPORT/METHODS:Here we describe two patients exhibiting high lactate concentrations in the setting of metabolic alkalemia. CONCLUSION/CONCLUSIONS:Lactate is not necessarily the direct cause of acid-base disturbances, and there is no fixed relationship between lactate and the anion gap or between lactate and pH. The term "metabolic acidosis with hyperlactatemia" is more specific than "lactic acidosis" and thus more appropriate.