Neurons in the PFC are typically activated by different cognitive tasks, and also by different stimuli and abstract variables within these tasks. A single neuron's selectivity for a given stimulus dimension often changes depending on its context, a phenomenon known as nonlinear mixed selectivity (NMS). It has previously been hypothesized that NMS emerges as a result of training to perform tasks in different contexts. We tested this hypothesis directly by examining the neuronal responses of different PFC areas before and after male monkeys were trained to perform different working memory tasks involving visual stimulus locations and/or shapes. We found that training induces a modest increase in the proportion of PFC neurons with NMS exclusively for spatial working memory, but not for shape working memory tasks, with area 9/46 undergoing the most significant increase in NMS cell proportion. We also found that increased working memory task complexity, in the form of simultaneously storing location and shape c...

During music listening, humans routinely acquire the regularities of the acoustic sequences and use them to anticipate and interpret the ongoing melody. Specifically, in line with this predictive framework, it is thought that brain responses during such listening reflect a comparison between the bottom-up sensory responses and top-down prediction signals generated by an internal model that embodies the music exposure and expectations of the listener. To attain a clear view of these predictive responses, previous work has eliminated the sensory inputs by inserting artificial silences (or sound omissions) that leave behind only the corresponding predictions of the thwarted expectations. Here, we demonstrate a new alternate approach in which we decode the predictive electroencephalography (EEG) responses to the silent intervals that are naturally interspersed within the music. We did this as participants (experiment 1, 20 participants, 10 female; experiment 2, 21 participants, 6 female) listened or imagined B...

Temporal costs influence reward-based decisions. This is commonly studied in temporal discounting tasks that involve choosing between cues signaling an imminent reward option or a delayed reward option. However, it is unclear whether the temporal delay before a reward can alter the value of that option. To address this, we identified the relative preference between different flavored rewards during a free-feeding test using male and female rats. Animals underwent training where either the initial preferred or the initial less preferred reward was delivered noncontingently. By manipulating the intertrial interval during training sessions, we could determine whether temporal delays impact reward preference in a subsequent free-feeding test. Rats maintained their initial preference if the same delays were used across all training sessions. When the initial less preferred option was delivered after short delays (high reward rate) and the initial preferred option was delivered after long delays (low reward rate...

Neuron migration is a hallmark of nervous system development that allows gathering of neurons from different origins for assembling of functional neuronal circuits. Cortical inhibitory interneurons arise in the ventral telencephalon and migrate tangentially forming three transient migratory streams in the cortex before reaching the final laminar destination. Although migration defects lead to the disruption of inhibitory circuits and are linked to aspects of psychiatric disorders such as autism and schizophrenia, the molecular mechanisms controlling cortical interneuron development and final layer positioning are incompletely understood. Here, we show that mouse embryos with a double deletion of FLRT2 and FLRT3 genes encoding cell adhesion molecules exhibit an abnormal distribution of interneurons within the streams during development, which in turn, affect the layering of somatostatin+ interneurons postnatally. Mechanistically, FLRT2 and FLRT3 proteins act in a noncell-autonomous manner, possibly through ...

Both nucleus reuniens and the anterior thalamic nuclei are densely interconnected with medial cortical and hippocampal areas, connections that reflect their respective contributions to learning and memory. To better appreciate their comparative roles, pairs of different retrograde tracers were placed in these two thalamic sites in adult rats. Both thalamic sites receive modest cortical inputs from layer V that contrasted with much denser projections from layer VI. Despite frequent overlap in layer VI, ventral prefrontal and anterior cingulate inputs to nucleus reuniens were concentrated in the deepest sublayer (VIb). Meanwhile, inputs to the anterior thalamic nuclei originated more evenly from both sublayers VIa and VIb, with the result that they were often located more superficially than the projections to nucleus reuniens. Again, while the many hippocampal (subiculum) neurons projecting to nucleus reuniens and the anterior thalamic nuclei were partially intermingled within the deep cellular parts of the ...

The ability to adapt under significant adversity, defined as psychological resilience, is instrumental in preventing stress-related disorders. An important aspect of resilience is the capacity to endure affective distress when in pursuit of goals, also known as distress tolerance. Evidence that links intrinsic baseline interactions within large-scale functional networks with performance under distress remains missing. We hypothesized that the anterior cingulate cortex (ACC) may engage in distress tolerance because of its involvement in attention and emotion regulation. Accordingly, we tested whether behavioral performance under distress is associated with baseline resting-state ACC functional connectivity (FC). Distress tolerance was measured in 97 participants using the behavioral indicator of resiliency to distress (BIRD) task. Analyses contrasted participants who quit the task before its designated termination ( n  = 51) with those who persisted throughout it ( n  = 46). Seed-based FC analysis indicated...

Frustrative nonreward (FN) is a construct in the Negative Valence Systems domain of the Research Domain Criteria (RDoC) from the National Institute of Mental Health. An organism’s response to frustrating situations (e.g., inability to obtain an expected reward) has broad implications for a variety of neuropsychiatric conditions, including substance use disorders. The current project developed a first of its kind rat operant behavioral model of FN based loosely on the human Point Subtraction Aggression Paradigm (PSAP). The current study shows that individual differences in FN for sucrose pellets are consistent across sessions at baseline and that the task is sensitive to reward size in male rats. More importantly, high FN behavior for sucrose predicts early “breaking” for intravenous fentanyl self-administration under a progressive ratio (PR) schedule. These results solidify frustration/ FN as an important factor for substance use disorders in addition to craving, impulsivity, and habit.

Understanding masseter muscle (MM) innervation is critical for the study of cell-specific mechanisms of pain induced by temporomandibular disorder (TMDs) or after facial surgery. Here, we identified trigeminal (TG) sensory neuronal subtypes (MM TG neurons) innervating MM fibers, masseteric fascia, tendons, and adjusted tissues. A combination of patch clamp electrophysiology and immunohistochemistry (IHC) on TG neurons back-traced from reporter mouse MM found nine distinct subtypes of MM TG neurons. Of these neurons, 24% belonged to non-peptidergic IB-4+/TRPA1– or IB-4+/TRPA1+ groups, while two TRPV1+ small-sized neuronal groups were classified as peptidergic/CGRP+. One small-sized CGRP+ neuronal group had a unique electrophysiological profile and were recorded from Nav1.8– or trkC+ neurons. The remaining CGRP+ neurons were medium-sized, could be divided into Nav1.8–/trkC– and Nav1.8low/trkC+ clusters, and showed large 5HT-induced current. The final two MM TG neuronal groups were trkC+ and had no Nav1.8 and...

Team flow occurs when a group functions in a high task engagement to achieve a goal, commonly seen in performance and sports. Team flow can enable enhanced positive experiences, as compared with individual flow or regular socializing. However, the neural basis for this enhanced behavioral state remains unclear. Here, we identified neural correlates (NCs) of team flow in human participants using a music rhythm task with electroencephalogram hyperscanning. Experimental manipulations held the motor task constant while disrupting the corresponding hedonic music to interfere with the flow state or occluding the partner’s positive feedback to impede team interaction. We validated these manipulations by using psychometric ratings and an objective measure for the depth of flow experience, which uses the auditory-evoked potential (AEP) of a task-irrelevant stimulus. Spectral power analysis at both the scalp sensors and anatomic source levels revealed higher β-γ power specific to team flow in the left middle tempora...

Human infants who suffer from intrauterine growth restriction (IUGR), which is a failure to attain their genetically predetermined weight, are at increased risk for postnatal learning and memory deficits. Hippocampal dentate gyrus (DG) granule neurons play an important role in memory formation; however, it is unknown whether IUGR affects embryonic DG neurogenesis, which could provide a potential mechanism underlying abnormal postnatal learning and memory function. Using a mouse model of the most common cause of IUGR, induced by hypertensive disease of pregnancy, we first assessed adult learning and memory function. We quantified the percentages of embryonic hippocampal DG neural stem cells (NSCs) and progenitor cells and developing glutamatergic granule neurons, as well as hippocampal volumes and neuron cell count and morphology 18 and 40 d after delivery. We characterized the differential embryonic hippocampal transcriptomic pathways between appropriately grown and IUGR mouse offspring. We found that IUGR...