Neural dynamics of choice: single-trial analysis of decision-related activity in parietal cortex.

Previous neurophysiological studies of perceptual decision-making have focused on single-unit activity, providing insufficient information about how individual decisions are accomplished. For the first time, we recorded simultaneously from multiple decision-related neurons in parietal cortex of monkeys performing a perceptual decision task and used these recordings to analyze the neural dynamics during single trials. We demonstrate that decision-related lateral intraparietal area neurons typically undergo gradual changes in firing rate during individual decisions, as predicted by mechanisms based on continuous integration of sensory evidence. Furthermore, we identify individual decisions that can be described as a change of mind: the decision circuitry was transiently in a state associated with a different choice before transitioning into a state associated with the final choice. These changes of mind reflected in monkey neural activity share similarities with previously reported changes of mind reflected in human behavior.

Local computation of decision-relevant net sensory evidence in parietal cortex.

To investigate the contribution of parietal cortex to perceptual decisions, we trained monkeys on a perceptual decision task that allowed simultaneous experimental control over how much sensory evidence was provided for each of 3 possible alternative choices and recorded single unit activity and local field potentials (LFPs) from the lateral intraparietal area (LIP). While both the behavior and the spiking activity were largely determined by the difference between how much supporting sensory evidence was provided for a particular choice (pro evidence) and how much sensory evidence was provided for the other alternatives (anti evidence), the LFP reflected roughly the sum of these 2 components. Furthermore, the firing rates showed an earlier influence of the anti evidence than the pro evidence. These observations indicate that LIP does not simply receive already precomputed decision signals but that it plays an active role in computing the decision-relevant net sensory evidence and that this local computation is reflected in the LFP. The results further demonstrate that the competition between the different alternatives cannot solely be mediated by lateral or feedback inhibition, as proposed by a major class of decision models but that feedforward inhibition makes an important contribution.

Neuronal mechanisms and attentional modulation of corticothalamic α oscillations.

Field potential oscillations in the ∼10 Hz range are known as the alpha rhythm. The genesis and function of alpha has been the subject of intense investigation for the past 80 years. Whereas early work focused on the thalamus as the pacemaker of alpha rhythm, subsequent slice studies revealed that pyramidal neurons in the deep layers of sensory cortices are capable of oscillating in the alpha frequency range independently. How thalamic and cortical generating mechanisms in the intact brain might interact to shape the organization and function of alpha oscillations remains unclear. We addressed this problem by analyzing laminar profiles of local field potential and multiunit activity (MUA) recorded with linear array multielectrodes from the striate cortex of two macaque monkeys performing an intermodal selective attention task. Current source density (CSD) analysis was combined with CSD-MUA coherence to identify intracortical alpha current generators and assess their potential for pacemaking. Coherence and Granger causality analysis was applied to delineate the patterns of interaction among different alpha current generators. We found that (1) separable alpha current generators are located in superficial, granular, and deep layers, with both layer 4C and deep layers containing primary local pacemaking generators, suggesting the involvement of the thalamocortical network, and (2) visual attention reduces the magnitude of alpha oscillations as well as the level of alpha interactions, consistent with numerous reports of occipital alpha reduction with visual attention in human EEG. There is also indication that alpha oscillations in the lateral geniculate cohere with those in V1.

Midbrain activity shapes high-level visual properties in the primate temporal cortex.

Recent fMRI experiments identified an attention-related region in the macaque temporal cortex, here called the floor of the superior temporal sulcus (fSTS), as the primary cortical target of superior colliculus (SC) activity. However, it remains unclear which aspects of attention are processed by fSTS neurons and how or why these might depend on SC activity. Here, we show that SC inactivation decreases attentional modulations in fSTS neurons by increasing their activity for ignored stimuli in addition to decreasing their activity for attended stimuli. Neurons in the fSTS also exhibit event-related activity during attention tasks linked to detection performance, and this link is eliminated during SC inactivation. Finally, fSTS neurons respond selectively to particular visual objects, and this selectivity is reduced markedly during SC inactivation. These diverse, high-level properties of fSTS neurons all involve visual signals that carry behavioral relevance. Their dependence on SC activity could reflect a circuit that prioritizes cortical processing of events detected subcortically.

Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque.

Microendoscopic calcium imaging with one-photon miniature microscopes enables unprecedented readout of neural circuit dynamics during active behavior in rodents. In this study, we describe successful application of this technology in the rhesus macaque, demonstrating plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from large populations of neurons simultaneously in bilateral dorsal premotor cortices during performance of a naturalistic motor reach task. Imaging is stable over several months, allowing us to longitudinally track individual neurons and monitor their relationship to motor behavior over time. We observe neuronal calcium dynamics selective for reach direction, which we could use to decode the animal's trial-by-trial motor behavior. This work establishes head-mounted microendoscopic calcium imaging in macaques as a powerful approach for studying the neural circuit mechanisms underlying complex and clinically relevant behaviors, and it promises to greatly advance our understanding of human brain function, as well as its dysfunction in neurological disease.

Short-training Algorithm for Online Brain-machine Interfaces Using One-photon Microendoscopic Calcium Imaging.

Calcium imaging has great potential to be applied to online brain-machine interfaces (BMIs). As opposed to two-photon imaging settings, a one-photon microendoscopic imaging device can be chronically implanted and is subject to little motion artifacts. Traditionally, one-photon microendoscopic calcium imaging data are processed using the constrained nonnegative matrix factorization (CNMFe) algorithm, but this batched processing algorithm cannot be applied in real-time. An online analysis of calcium imaging data algorithm (or OnACIDe) has been proposed, but OnACIDe updates the neural components by repeatedly performing neuron identification frame-by-frame, which may decelerate the update speed if applying to online BMIs. For BMI applications, the ability to track a stable population of neurons in real-time has a higher priority over accurately identifying all the neurons in the field of view. By leveraging the fact that 1) microendoscopic recordings are rather stable with little motion artifacts and 2) the number of neurons identified in a short training period is sufficient for potential online BMI tasks such as cursor movements, we proposed the short-training CNMFe algorithm (stCNMFe) that skips motion correction and neuron identification processes to enable a more efficient BMI training program in a one-photon microendoscopic setting.

Neuronal mechanisms of cortical alpha oscillations in awake-behaving macaques.

Field potential oscillations at approximately 10 Hz (alpha rhythm) are widely noted in the visual cortices, but their physiological mechanisms and significance are poorly understood. In vitro studies have implicated pyramidal neurons in both infragranular and supragranular layers as pacemakers. The generality of these observations for the intact brain in the behaving subject is unknown. We analyzed laminar profiles of spontaneous local field potentials and multiunit activity (MUA) recorded with linear array multielectrodes from visual areas V2, V4, and inferotemporal (IT) cortex of two macaque monkeys during performance of a sensory discrimination task. Current source density (CSD) analysis was combined with CSD-MUA coherence to identify intracortical alpha current generators and their potential for alpha pacemaking. The role of each alpha current generator was further delineated by Granger causality analyses. In V2 and V4, alpha current generators were found in all layers, with the infragranular generator acting as primary local pacemaking generator. In contrast, in IT, alpha current generators were found only in supragranular and infragranular layers, with the supragranular generator acting as primary local pacemaking generator. The amplitude of alpha activity in V2 and V4 was negatively correlated with behavioral performance, whereas the opposite was true in IT. The alpha rhythm in IT thus appears to differ from that in the lower-order cortices, both in terms of its underlying physiological mechanism and its behavioral correlates. This work may help to reconcile some of the diverse findings and conclusions on the functional significance of alpha band oscillations in the visual system.

Spatial Attention Deficits Are Causally Linked to an Area in Macaque Temporal Cortex.

Spatial neglect is a common clinical syndrome involving disruption of the brain's attention-related circuitry, including the dorsocaudal temporal cortex. In macaques, the attention deficits associated with neglect can be readily modeled, but the absence of evidence for temporal cortex involvement has suggested a fundamental difference from humans. To map the neurological expression of neglect-like attention deficits in macaques, we measured attention-related fMRI activity across the cerebral cortex during experimental induction of neglect through reversible inactivation of the superior colliculus and frontal eye fields. During inactivation, monkeys exhibited hallmark attentional deficits of neglect in tasks using either motion or non-motion stimuli. The behavioral deficits were accompanied by marked reductions in fMRI attentional modulation that were strongest in a small region on the floor of the superior temporal sulcus; smaller reductions were also found in frontal eye fields and dorsal parietal cortex. Notably, direct inactivation of the mid-superior temporal sulcus (STS) cortical region identified by fMRI caused similar neglect-like spatial attention deficits. These results identify a putative macaque homolog to temporal cortex structures known to play a central role in human neglect.

Comparing frontal eye field and superior colliculus contributions to covert spatial attention.

The causal roles of the frontal eye fields (FEF) and superior colliculus (SC) in spatial selective attention have not been directly compared. Reversible inactivation is an established method for testing causality but comparing results between FEF and SC is complicated by differences in size and morphology of the two brain regions. Here we exploited the fact that inactivation of FEF and SC also changes the metrics of saccadic eye movements, providing an independent benchmark for the strength of the causal manipulation. Using monkeys trained to covertly perform a visual motion-change detection task, we found that inactivation of either FEF or SC could cause deficits in attention task performance. However, SC-induced attention deficits were found with saccade changes half the size needed to get FEF-induced attention deficits. Thus, performance in visual attention tasks is vulnerable to loss of signals from either structure, but suppression of SC activity has a more devastating effect.

Selective attention without a neocortex.

Selective attention refers to the ability to restrict neural processing and behavioral responses to a relevant subset of available stimuli, while simultaneously excluding other valid stimuli from consideration. In primates and other mammals, descriptions of this ability typically emphasize the neural processing that takes place in the cerebral neocortex. However, non-mammals such as birds, reptiles, amphibians and fish, which completely lack a neocortex, also have the ability to selectively attend. In this article, we survey the behavioral evidence for selective attention in non-mammals, and review the midbrain and forebrain structures that are responsible. The ancestral forms of selective attention are presumably selective orienting behaviors, such as prey-catching and predator avoidance. These behaviors depend critically on a set of subcortical structures, including the optic tectum (OT), thalamus and striatum, that are highly conserved across vertebrate evolution. In contrast, the contributions of different pallial regions in the forebrain to selective attention have been subject to more substantial changes and reorganization. This evolutionary perspective makes plain that selective attention is not a function achieved de novo with the emergence of the neocortex, but instead is implemented by circuits accrued and modified over hundreds of millions of years, beginning well before the forebrain contained a neocortex. Determining how older subcortical circuits interact with the more recently evolved components in the neocortex will likely be crucial for understanding the complex properties of selective attention in primates and other mammals, and for identifying the etiology of attention disorders.

Brain regions modulated during covert visual attention in the macaque.

Neurophysiological studies of covert visual attention in monkeys have emphasized the modulation of sensory neural responses in the visual cortex. At the same time, electrophysiological correlates of attention have been reported in other cortical and subcortical structures, and recent fMRI studies have identified regions across the brain modulated by attention. Here we used fMRI in two monkeys performing covert attention tasks to reproduce and extend these findings in order to help establish a more complete list of brain structures involved in the control of attention. As expected from previous studies, we found attention-related modulation in frontal, parietal and visual cortical areas as well as the superior colliculus and pulvinar. We also found significant attention-related modulation in cortical regions not traditionally linked to attention - mid-STS areas (anterior FST and parts of IPa, PGa, TPO), as well as the caudate nucleus. A control experiment using a second-order orientation stimulus showed that the observed modulation in a subset of these mid-STS areas did not depend on visual motion. These results identify the mid-STS areas (anterior FST and parts of IPa, PGa, TPO) and caudate nucleus as potentially important brain regions in the control of covert visual attention in monkeys.

Trial-by-trial estimation of amplitude and latency variability in neuronal spike trains.

The rate function underlying single-trial spike trains can vary from trial to trial. We propose to estimate the amplitude and latency variability in single-trial neuronal spike trains on a trial-by-trial basis. The firing rate over a trial is modeled by a family of rate profiles with trial-invariant waveform and trial-dependent amplitude scaling factors and latency shifts. Using a Bayesian inference framework we derive an iterative fixed-point algorithm from which the single-trial amplitude scaling factors and latency shifts are estimated. We test the performance of the algorithm on simulated data and then apply it to actual neuronal recordings from the sensorimotor cortex of the monkey.

Attention as an effect not a cause.

Attention is commonly thought to be important for managing the limited resources available in sensory areas of the neocortex. Here we present an alternative view that attention arises as a byproduct of circuits centered on the basal ganglia involved in value-based decision making. The central idea is that decision making depends on properly estimating the current state of the animal and its environment and that the weighted inputs to the currently prevailing estimate give rise to the filter-like properties of attention. After outlining this new framework, we describe findings from physiological, anatomical, computational, and clinical work that support this point of view. We conclude that the brain mechanisms responsible for attention employ a conserved circuit motif that predates the emergence of the neocortex.