A reference tissue forward model for improved PET accuracy using within-scan displacement studies.

We report a novel forward-model implementation of the full reference tissue model (fFTRM) that addresses the fast-exchange approximation employed by the simplified reference tissue model (SRTM) by incorporating a non-zero dissociation time constant from the specifically bound compartment. The forward computational approach avoided errors associated with noisy and nonorthogonal basis functions using an inverse linear model. Compared to analysis by a multilinear single-compartment reference tissue model (MRTM), fFTRM provided improved accuracy for estimation of binding potentials at early times in the scan, with no worse reproducibility across sessions.

Stimulation of the ventral tegmental area induces visual cortical plasticity at the neuronal level.

fMRI studies have shown that pairing a task-irrelevant visual feature with electrical micro-stimulation of the ventral tegmental area (VTA-EM) is sufficient to increase the sensory cortical representation of the paired feature and to improve perceptual performance. However, since fMRI provides an indirect measure of neural activity, the neural response changes underlying the fMRI activations are unknown. Here, we pair a task-irrelevant grating orientation with VTA-EM while attention is directed to a difficult orthogonal task.

Electrical stimulation of the macaque ventral tegmental area drives category-selective learning without attention.

Perception improves by repeated practice with visual stimuli, a phenomenon known as visual perceptual learning (VPL). The interplay of attentional and neuromodulatory reward signals is hypothesized to cause these behavioral and associated neuronal changes, although VPL can occur without attention (i.e.

Selective Mesoaccumbal Pathway Inactivation Affects Motivation but Not Reinforcement-Based Learning in Macaques.

Rodent studies have demonstrated the role of the mesoaccumbal circuit in reinforcement-based learning. Importantly, however, while phasic activity of the ventral tegmental area (VTA) contributes to reinforcement learning, rodent evidence suggests that slow changes in tonic VTA activity and associated accumbal dopamine release help regulate motivational behavior. Nonetheless, the consequences of sustained blockage of the mesoaccumbal circuit for motivation and reinforcement learning have not yet been examined in primates.

Frequency- and State-Dependent Network Effects of Electrical Stimulation Targeting the Ventral Tegmental Area in Macaques.

The ventral tegmental area (VTA) is a midbrain structure at the heart of the dopaminergic system underlying adaptive behavior. Endogenous firing rates of dopamine cells in the VTA vary from fast phasic bursts to slow tonic activity. Artificial perturbations of the VTA, through electrical or optogenetic stimulation methods, generate different and sometimes even contrasting behavioral outcomes depending on stimulation parameters such as frequency, amplitude, and pulse width.

Ventral midbrain stimulation induces perceptual learning and cortical plasticity in primates.

Practice improves perception and enhances neural representations of trained visual stimuli, a phenomenon known as visual perceptual learning (VPL). While attention to task-relevant stimuli plays an important role in such learning, Pavlovian stimulus-reinforcer associations are sufficient to drive VPL, even subconsciously. It has been proposed that reinforcement facilitates perceptual learning through the activation of neuromodulatory centers, but this has not been directly confirmed in primates.

In Vivo Identification of Thick, Thin, and Pale Stripes of Macaque Area V2 Using Submillimeter Resolution (f)MRI at 3 T.

Primate area V2 contains a repetitive pattern of thick, thin and pale cytochrome oxidase stripes that are characterized by largely discrete in- and output channels, as well as differences in function, and myelo- and cytoarchitecture. Stripes have been identified mainly using microscope-based imaging of tiny portions of superficially located V2, or by postmortem methods, hence, the quest for (quasi) noninvasive tools to study these mesoscale functional units. Only recently, stripe-like V2 patterns have been demonstrated in humans with high-field (functional) magnetic resonance imaging (f)MRI, but in both such studies only 2 stripe compartments could be identified.

Attention Shifts Recruit the Monkey Default Mode Network.

A unifying function associated with the default mode network (DMN), which is more active during rest than under active task conditions, has been difficult to define. The DMN is activated during monitoring the external world for unexpected events, as a sentinel, and when humans are engaged in high-level internally focused tasks. The existence of DMN correlates in other species, such as mice, challenge the idea that internally focused, high-level cognitive operations, such as introspection, autobiographical memory retrieval, planning the future, and predicting someone else's thoughts, are evolutionarily preserved defining properties of the DMN.

Functional Similarity of Medial Superior Parietal Areas for Shift-Selective Attention Signals in Humans and Monkeys.

We continually shift our attention between items in the visual environment. These attention shifts are usually based on task relevance (top-down) or the saliency of a sudden, unexpected stimulus (bottom-up), and are typically followed by goal-directed actions. It could be argued that any species that can covertly shift its focus of attention will rely on similar, evolutionarily conserved neural substrates for processing such shift-signals.

Should I Stay or Should I Go?

In this issue of Neuron, Lee et al. (2016) assessed the brain-wide effects of stimulating the direct and indirect pathway by optogenetic activation of D1 and D2 striatal neurons. This work demonstrates the exquisite power of combining cell-type-specific perturbation methods with focal and whole-brain measurements of brain activity.

Noisy neurons, neat networks.

In this issue of Neuron, Kiani et al. (2015) show that the correlated activity of multiple simultaneously recorded neurons can be used to identify, in a completely un-biased manner, distinct functional domains within prefrontal and (pre)motor cortex of macaque monkeys.

Role of the primate ventral tegmental area in reinforcement and motivation.

Monkey electrophysiology suggests that the activity of the ventral tegmental area (VTA) helps regulate reinforcement learning and motivated behavior, in part by broadcasting prediction error signals throughout the reward system. However, electrophysiological studies do not allow causal inferences regarding the activity of VTA neurons with respect to these processes because they require artificial manipulation of neuronal firing. Rodent studies fulfilled this requirement by demonstrating that electrical and optogenetic VTA stimulation can induce learning and modulate downstream structures.

Dopaminergic reward signals selectively decrease fMRI activity in primate visual cortex.

Stimulus-reward coupling without attention can induce highly specific perceptual learning effects, suggesting that reward triggers selective plasticity within visual cortex. Additionally, dopamine-releasing events-temporally surrounding stimulus-reward associations-selectively enhance memory. These forms of plasticity may be evoked by selective modulation of stimulus representations during dopamine-inducing events.

Neural correlates of the formation and retention of cocaine-induced stimulus-reward associations.

Background: Cocaine can elicit drug-seeking behavior for drug-predicting stimuli, even after a single stimulus-cocaine pairing. Although orbitofrontal cortex is thought to be important during encoding and maintenance of stimulus-reward value, we still lack a comprehensive model of the neural circuitry underlying this cognitive process.

Methods: We studied the conditioned effects of cocaine with monkey functional magnetic resonance imaging and classical conditioning by pairing a visual shape (conditioning stimulus [CS+]) with a noncontingent cocaine infusion; a control stimulus was never paired.

Modulation of the contrast response function by electrical microstimulation of the macaque frontal eye field.

Spatial attention influences representations in visual cortical areas as well as perception. Some models predict a contrast gain, whereas others a response or activity gain when attention is directed to a contrast-varying stimulus. Recent evidence has indicated that microstimulating the frontal eye field (FEF) can produce modulations of cortical area V4 neuronal firing rates that resemble spatial attention-like effects, and we have shown similar modulations of functional magnetic resonance imaging (fMRI) activity throughout the visual system.

Visual field map clusters in macaque extrastriate visual cortex.

The macaque visual cortex contains >30 different functional visual areas, yet surprisingly little is known about the underlying organizational principles that structure its components into a complete "visual" unit. A recent model of visual cortical organization in humans suggests that visual field maps are organized as clusters. Clusters minimize axonal connections between individual field maps that represent common visual percepts, with different clusters thought to carry out different functions.

Bottom-up dependent gating of frontal signals in early visual cortex.

The frontal eye field (FEF) is one of several cortical regions thought to modulate sensory inputs. Moreover, several hypotheses suggest that the FEF can only modulate early visual areas in the presence of a visual stimulus. To test for bottom-up gating of frontal signals, we microstimulated subregions in the FEF of two monkeys and measured the effects throughout the brain with functional magnetic resonance imaging.