Rhesus Monkeys' Valuation of Vocalizations during a Free-Choice Task

Adaptive behavior requires that animals integrate current and past information with their decision-making. One important type of information is auditory-communication signals (i.e., species-specific vocalizations). Here, we tested how rhesus monkeys incorporate the opportunity to listen to different species-specific vocalizations into their decision-making processes. In particular, we tested how monkeys value these vocalizations relative to the opportunity to get a juice reward. To test this hypothesis, monkeys chose one of two targets to get a varying juice reward; at one of those targets, in addition to the juice reward, a vocalization was presented. By titrating the juice amounts at the two targets, we quantified the relationship between the monkeys' juice choices relative to the opportunity to listen to a vocalization. We found that, rhesus were not willing to give up a large juice reward to listen to vocalizations indicating that, relative to a juice reward, listening to vocalizations has a low value

Prefrontal Neurons Predict Choices during an Auditory Same-Different Task

SummaryThe detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2–5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6–8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a “reference” stimulus that were followed by a “test” stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task

Prefrontal Activity Predicts Monkeys' Decisions During an Auditory Category Task

The neural correlates that relate auditory categorization to aspects of goal-directed behavior, such as decision-making, are not well understood. Since the prefrontal cortex (PFC) plays an important role in executive function and the categorization of auditory objects, we hypothesized that neural activity in the PFC should predict an animal's behavioral reports (decisions) during a category task. To test this hypothesis, we tested PFC activity that was recorded while monkeys categorized human spoken words (Russ et al., 2008b). We found that activity in the ventrolateral PFC, on average, correlated best with the monkeys' choices than with the auditory stimuli. This finding demonstrates a direct link between PFC activity and behavioral choices during a non-spatial auditory task

The Contribution of Primary Auditory Cortex to Auditory Categorization in Behaving Monkeys

The specific contribution of core auditory cortex to auditory perception –such as categorization– remains controversial. To identify a contribution of the primary auditory cortex (A1) to perception, we recorded A1 activity while monkeys reported whether a temporal sequence of tone bursts was heard as having a “small” or “large” frequency difference. We found that A1 had frequency-tuned responses that habituated, independent of frequency content, as this auditory sequence unfolded over time. We also found that A1 firing rate was modulated by the monkeys’ reports of “small” and “large” frequency differences; this modulation correlated with their behavioral performance. These findings are consistent with the hypothesis that A1 contributes to the processes underlying auditory categorization

The Neurophysiology of Functionally Meaningful Categories: Macaque Ventrolateral Prefrontal Cortex Plays a Critical Role in Spontaneous Categorization of Species-Specific Vocalizations

Neurophysiological studies in nonhuman primates have demonstrated that the prefrontal cortex (PFC) plays a critical role in the acquisition of learned categories following training. What is presently unclear is whether this cortical area also plays a role in spontaneous recognition and discrimination of natural categories. Here, we explore this possibility by recording from neurons in the PFC while rhesus listen to species-specific vocalizations that vary in terms of their social function and acoustic morphology. We found that ventral prefrontal cortex (vPFC) activity, on average, did not differentiate between food calls that were associated with the same functional category, despite having different acoustic properties. In contrast, vPFC activity differentiated between food calls associated with different functional classes and specifically, information about the quality and motivational value of the food. These results suggest that the vPFC is involved in the categorization of socially meaningful signals, thereby both extending its previously conceived role in the acquisition of learned categories and showing the significance of using natural categorical distinctions in the study of neural mechanisms.Psycholog

Modulation of Cross-Frequency Coupling by Novel and Repeated Stimuli in the Primate Ventrolateral Prefrontal Cortex

Adaptive behavior depends on an animal’s ability to ignore uninformative stimuli, such as repeated presentations of the same stimulus, and, instead, detect informative, novel stimuli in its environment. The primate prefrontal cortex (PFC) is known to play a central role in this ability. However, the neural mechanisms underlying the ability to differentiate between repeated and novel stimuli are not clear. We hypothesized that the coupling between different frequency bands of the local field potential (LFP) underlies the PFC’s role in differentiating between repeated and novel stimuli. Specifically, we hypothesized that whereas the presentation of a novel-stimulus induces strong cross-frequency coupling, repeated presentations of the same stimulus attenuates this coupling. To test this hypothesis, we recorded LFPs from the ventrolateral PFC (vPFC) of rhesus monkeys while they listened to a novel vocalization and repeated presentations of the same vocalization. We found that the cross-frequency coupling between the gamma-band amplitude and theta-band phase of the LFP was modulated by repeated presentations of a stimulus. During the first (novel) presentation of a stimulus, gamma-band activity was modulated by the theta-band phase. However, with repeated presentations of the same stimulus, this cross-frequency coupling was attenuated. These results suggest that cross-frequency coupling may play a role in the neural computations that underlie the differentiation between novel and repeated stimuli in the vPFC

Time as a supervisor: temporal regularity and auditory object learning

Sensory systems appear to learn to transform incoming sensory information into perceptual representations, or “objects,” that can inform and guide behavior with minimal explicit supervision. Here, we propose that the auditory system can achieve this goal by using time as a supervisor, i.e., by learning features of a stimulus that are temporally regular. We will show that this procedure generates a feature space sufficient to support fundamental computations of auditory perception. In detail, we consider the problem of discriminating between instances of a prototypical class of natural auditory objects, i.e., rhesus macaque vocalizations. We test discrimination in two ethologically relevant tasks: discrimination in a cluttered acoustic background and generalization to discriminate between novel exemplars. We show that an algorithm that learns these temporally regular features affords better or equivalent discrimination and generalization than conventional feature-selection algorithms, i.e., principal component analysis and independent component analysis. Our findings suggest that the slow temporal features of auditory stimuli may be sufficient for parsing auditory scenes and that the auditory brain could utilize these slowly changing temporal features

The Impact of Insulin Pump Therapy on Glycemic Profiles in Patients with Type 2 Diabetes: Data from the OpT2mise Study

Background: The OpT2mise randomized trial was designed to compare the effects of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) on glucose profiles in patients with type 2 diabetes. Research Design and Methods: Patients with glycated hemoglobin (HbA1c) levels of ≥8% (64 mmol/mol) and ≤12% (108 mmol/mol) despite insulin doses of 0.7-1.8 U/kg/day via MDI were randomized to CSII (n=168) or continued MDI (n=163). Changes in glucose profiles were evaluated using continuous glucose monitoring data collected over 6-day periods before and 6 months after randomization. Results: After 6 months, reductions in HbA1c levels were significantly greater with CSII (-1.1±1.2% [-12.0±13.1 mmol/mol]) than with MDI (-0.4±1.1% [-4.4±12.0 mmol/mol]) (P<0.001). Similarly, compared with patients receiving MDI, those receiving CSII showed significantly greater reductions in 24-h mean sensor glucose (SG) (treatment difference, -17.1 mg/dL; P=0.0023), less exposure to SG >180 mg/dL (-12.4%; P=0.0004) and SG >250 mg/dL (-5.5%; P=0.0153), and more time in the SG range of 70-180 mg/dL (12.3%; P=0.0002), with no differences in exposure to SG<70 mg/dL or in glucose variability. Changes in postprandial (4-h) glucose area under the curve >180 mg/dL were significantly greater with CSII than with MDI after breakfast (-775.9±1,441.2 mg/dL/min vs. -160.7±1,074.1 mg/dL/min; P=0.0015) and after dinner (-731.4±1,580.7 mg/dL/min vs. -71.1±1,083.5 mg/dL/min; P=0.0014). Conclusions: In patients with suboptimally controlled type 2 diabetes, CSII significantly improves selected glucometrics, compared with MDI, without increasing the risk of hypoglycemia

FRET-Based Identification of mRNAs Undergoing Translation

We present proof-of-concept in vitro results demonstrating the feasibility of using single molecule fluorescence resonance energy transfer (smFRET) measurements to distinguish, in real time, between individual ribosomes programmed with several different, short mRNAs. For these measurements we use either the FRET signal generated between two tRNAs labeled with different fluorophores bound simultaneously in adjacent sites to the ribosome (tRNA-tRNA FRET) or the FRET signal generated between a labeled tRNA bound to the ribosome and a fluorescent derivative of ribosomal protein L1 (L1-tRNA FRET). With either technique, criteria were developed to identify the mRNAs, taking into account the relative activity of the mRNAs. These criteria enabled identification of the mRNA being translated by a given ribosome to within 95% confidence intervals based on the number of identified FRET traces. To upgrade the approach for natural mRNAs or more complex mixtures, the stoichiometry of labeling should be enhanced and photobleaching reduced. The potential for porting these methods into living cells is discussed