Putative cell-type-specific multiregional mode in posterior parietal cortex during coordinated visual behavior.

In the reach and saccade regions of the posterior parietal cortex (PPC), multiregional communication depends on the timing of neuronal activity with respect to beta-frequency (10-30 Hz) local field potential (LFP) activity, termed dual coherence. Neural coherence is believed to reflect neural excitability, whereby spiking tends to occur at a particular phase of LFP activity, but the mechanisms of multiregional dual coherence remain unknown. Here, we investigate dual coherence in the PPC of non-human primates performing eye-hand movements. We computationally model dual coherence in terms of multiregional neural excitability and show that one latent component, a multiregional mode, reflects shared excitability across distributed PPC populations. Analyzing the power in the multiregional mode with respect to different putative cell types reveals significant modulations with the spiking of putative pyramidal neurons and not inhibitory interneurons. These results suggest a specific role for pyramidal neurons in dual coherence supporting multiregional communication in PPC.

Excitatory/Inhibitory Responses Shape Coherent Neuronal Dynamics Driven by Optogenetic Stimulation in the Primate Brain.

Coherent neuronal dynamics play an important role in complex cognitive functions. Optogenetic stimulation promises to provide new ways to test the functional significance of coherent neural activity. However, the mechanisms by which optogenetic stimulation drives coherent dynamics remain unclear, especially in the nonhuman primate brain. Here, we perform computational modeling and experiments to study the mechanisms of optogenetic-stimulation-driven coherent neuronal dynamics in three male nonhuman primates. Neural responses arise from stimulation-evoked, temporally dynamic excitatory (E) and inhibitory (I) activity. Spiking activity is more likely to occur during E/I imbalances. Thus the relative difference in the driven E and I responses precisely controls spike timing by forming a brief time interval of increased spiking likelihood. Experimental results agree with parameter-dependent predictions from the computational models. These results demonstrate that optogenetic stimulation driven coherent neuronal dynamics are governed by the temporal properties of E/I activity. Transient imbalances in excitatory and inhibitory activity may provide a general mechanism for generating coherent neuronal dynamics without the need for an oscillatory generator.SIGNIFICANCE STATEMENT We examine how coherent neuronal dynamics arise from optogenetic stimulation in the primate brain. Using computational models and experiments, we demonstrate that coherent spiking and local field potential activity is generated by stimulation-evoked responses of excitatory and inhibitory activity in networks, extending the growing literature on neuronal dynamics. These responses create brief time intervals of increased spiking tendency and are consistent with previous observations in the literature that balanced excitation and inhibition controls spike timing, suggesting that optogenetic-stimulation-driven coherence may arise from intrinsic E/I balance. Most importantly, our results are obtained in nonhuman primates and thus will play a leading role in driving the use of causal manipulations with optogenetic tools to study higher cognitive functions in the primate brain.

Parametric models to relate spike train and LFP dynamics with neural information processing.

Spike trains and local field potentials (LFPs) resulting from extracellular current flows provide a substrate for neural information processing. Understanding the neural code from simultaneous spike-field recordings and subsequent decoding of information processing events will have widespread applications. One way to demonstrate an understanding of the neural code, with particular advantages for the development of applications, is to formulate a parametric statistical model of neural activity and its covariates. Here, we propose a set of parametric spike-field models (unified models) that can be used with existing decoding algorithms to reveal the timing of task or stimulus specific processing. Our proposed unified modeling framework captures the effects of two important features of information processing: time-varying stimulus-driven inputs and ongoing background activity that occurs even in the absence of environmental inputs. We have applied this framework for decoding neural latencies in simulated and experimentally recorded spike-field sessions obtained from the lateral intraparietal area (LIP) of awake, behaving monkeys performing cued look-and-reach movements to spatial targets. Using both simulated and experimental data, we find that estimates of trial-by-trial parameters are not significantly affected by the presence of ongoing background activity. However, including background activity in the unified model improves goodness of fit for predicting individual spiking events. Uncovering the relationship between the model parameters and the timing of movements offers new ways to test hypotheses about the relationship between neural activity and behavior. We obtained significant spike-field onset time correlations from single trials using a previously published data set where significantly strong correlation was only obtained through trial averaging. We also found that unified models extracted a stronger relationship between neural response latency and trial-by-trial behavioral performance than existing models of neural information processing. Our results highlight the utility of the unified modeling framework for characterizing spike-LFP recordings obtained during behavioral performance.

Only coherent spiking in posterior parietal cortex coordinates looking and reaching.

Here, we report that temporally patterned, coherent spiking activity in the posterior parietal cortex (PPC) coordinates the timing of looking and reaching. Using a spike-field approach, we identify a population of parietal area LIP neurons that fire spikes coherently with 15 Hz beta-frequency LFP activity. The firing rate of coherently active neurons predicts the reaction times (RTs) of coordinated reach-saccade movements but not of saccades when made alone. Area LIP neurons that do not fire coherently do not predict RT of either movement type. Similar beta-band LFP activity is present in the parietal reach region but not nearby visual area V3d. This suggests that coherent spiking activity in PPC can control reaches and saccades together. We propose that the neural mechanism of coordination involves a shared representation that acts to slow or speed movements together.

Spike-field activity in parietal area LIP during coordinated reach and saccade movements.

The posterior parietal cortex is situated between visual and motor areas and supports coordinated visually guided behavior. Area LIP in the intraparietal sulcus contains representations of visual space and has been extensively studied in the context of saccades. However, area LIP has not been studied during coordinated movements, so it is not known whether saccadic representations in area LIP are influenced by coordinated behavior. Here, we studied spiking and local field potential (LFP) activity in area LIP while subjects performed coordinated reaches and saccades or saccades alone to remembered target locations to test whether activity in area LIP is influenced by the presence of a coordinated reach. We find that coordination significantly changes the activity of individual neurons in area LIP, increasing or decreasing the firing rate when a reach is made with a saccade compared with when a saccade is made alone. Analyzing spike-field coherence demonstrates that area LIP neurons whose firing rate is suppressed during the coordinated task have activity temporally correlated with nearby LFP activity, which reflects the synaptic activity of populations of neurons. Area LIP neurons whose firing rate increases during the coordinated task do not show significant spike-field coherence. Furthermore, LFP power in area LIP is suppressed and does not increase when a coordinated reach is made with a saccade. These results demonstrate that area LIP neurons display different responses to coordinated reach and saccade movements, and that different spike rate responses are associated with different patterns of correlated activity. The population of neurons whose firing rate is suppressed is coherently active with local populations of LIP neurons. Overall, these results suggest that area LIP plays a role in coordinating visually guided actions through suppression of coherent patterns of saccade-related activity.

Reaction time correlations during eye-hand coordination: behavior and modeling.

During coordinated eye-hand movements, saccade reaction times (SRTs) and reach reaction times (RRTs) are correlated in humans and monkeys. Reaction times (RTs) measure the degree of movement preparation and can correlate with movement speed and accuracy. However, RTs can also reflect effector nonspecific influences, such as motivation and arousal. We use a combination of behavioral psychophysics and computational modeling to identify plausible mechanisms for correlations in SRTs and RRTs. To disambiguate nonspecific mechanisms from mechanisms specific to movement coordination, we introduce a dual-task paradigm in which a reach and a saccade are cued with a stimulus onset asynchrony (SOA). We then develop several variants of integrate-to-threshold models of RT, which postulate that responses are initiated when the neural activity encoding effector-specific movement preparation reaches a threshold. The integrator models formalize hypotheses about RT correlations and make predictions for how each RT should vary with SOA. To test these hypotheses, we trained three monkeys to perform the eye-hand SOA task and analyzed their SRTs and RRTs. In all three subjects, RT correlations decreased with increasing SOA duration. Additionally, mean SRT decreased with decreasing SOA, revealing facilitation of saccades with simultaneous reaches, as predicted by the model. These results are not consistent with the predictions of the models with common modulation or common input but are compatible with the predictions of a model with mutual excitation between two effector-specific integrators. We propose that RT correlations are not simply attributable to motivation and arousal and are a signature of coordination.

A likelihood method for computing selection times in spiking and local field potential activity.

The timing of neural responses to ongoing behavior is an important measure of the underlying neural processes. Neural processes are distributed across many different brain regions and measures of the timing of neural responses are routinely used to test relationships between different brain regions. Testing detailed models of functional neural circuitry underlying behavior depends on extracting information from single trials. Despite their importance, existing methods for analyzing the timing of information in neural signals on single trials remain limited in their scope and application. We develop a novel method for estimating the timing of information in neural activity that we use to measure selection times, when an observer can reliably use observations of neural activity to select between two descriptions of the activity. The method is designed to satisfy three criteria: selection times should be computed from single trials, they should be computed from both spiking and local field potential (LFP) activity, and they should allow us to make comparisons between different recordings. Our approach characterizes the timing of information in terms of an accumulated log-likelihood ratio (AccLLR), which distinguishes between two alternative hypotheses and uses the AccLLR to estimate the selection time. We develop the AccLLR procedure for binary discrimination using example recordings of spiking and LFP activity in the posterior parietal cortex of a monkey performing a memory-guided saccade task. We propose that the AccLLR method is a general and practical framework for the analysis of signal timing in the nervous system.

Allocentric spatial referencing of neuronal activity in macaque posterior cingulate cortex.

Neuronal activity in posterior cingulate cortex (CGp) is modulated by visual stimulation, saccades, and eye position, suggesting a role for this area in visuospatial transformations. The goal of this study was to determine whether neuronal responses in CGp are anchored to the eyes, head, or outside the body (allocentrically). To discriminate retinocentric from nonretinocentric spatial referencing, the activity of single CGp neurons was recorded while monkeys (Macaca mulatta) performed delayed-saccade trials initiated randomly from three different starting positions to a linear array of targets passing through the neuronal response field. For most neurons, tuning curves, segregated by fixation point, aligned more closely when plotted with respect to the display than when plotted with respect to the eye, suggesting a nonretinocentric frame of reference. A second experiment differentiated between spatial referencing in coordinates anchored to the head or body and allocentric spatial referencing. Monkeys shifted gaze from a central fixation point to the array of previously used targets both before and after whole-body rotation with respect to the display. For most neurons, tuning curves, segregated by fixation position, aligned more closely when plotted as a function of target position in the room than when plotted as a function of target position with respect to the monkey. These data indicate that a population of CGp neurons encodes visuospatial events in allocentric coordinates.

Visual and saccade-related activity in macaque posterior cingulate cortex.

Previous neurophysiological studies have reported that neurons in posterior cingulate cortex (PCC) respond after eye movements, and that these responses may vary with ambient illumination. In monkeys, PCC neurons also respond after the illumination of large visual patterns but not after the illumination of small visual targets on either reflexive saccade tasks or peripheral attention tasks. These observations suggest that neuronal activity in PCC is modulated by behavioral context, which varies with the timing and spatial distribution of visual and oculomotor events. To test this hypothesis, we measured the spatial and temporal response properties of single PCC neurons in monkeys performing saccades in which target location and movement timing varied unpredictably. Specifically, an unsignaled delay between target onset and movement onset permitted us to temporally dissociate changes in PCC activity associated with either event. Response fields constructed from these data demonstrated that many PCC neurons were activated after the illumination of small contralateral visual targets, as well as after the onset of contraversive saccades guided by those targets. In addition, the PCC population maintained selectivity for small contralateral targets during delays of up to 600 ms. Overall, PCC activation was highly variable trial to trial and selective for a broad range of directions and amplitudes. Planar functions described response fields nearly as well as broadly tuned 2-dimensional Gaussian functions. Additionally, the overall responsiveness of PCC neurons decreased during delays when both a fixation stimulus and a saccade target were visible, suggesting a modulation by divided attention. Finally, the strength of the neuronal response after target onset was correlated with saccade accuracy on delayed-saccade trials. Thus PCC neurons may signal salient visual and oculomotor events, consistent with a role in visual orienting and attention.

Emotion-attention network interactions during a visual oddball task.

Emotional and attentional functions are known to be distributed along ventral and dorsal networks in the brain, respectively. However, the interactions between these systems remain to be specified. The present study used event-related functional magnetic resonance imaging (fMRI) to investigate how attentional focus can modulate the neural activity elicited by scenes that vary in emotional content. In a visual oddball task, aversive and neutral scenes were presented intermittently among circles and squares. The squares were frequent standard events, whereas the other novel stimulus categories occurred rarely. One experimental group [N=10] was instructed to count the circles, whereas another group [N=12] counted the emotional scenes. A main effect of emotion was found in the amygdala (AMG) and ventral frontotemporal cortices. In these regions, activation was significantly greater for emotional than neutral stimuli but was invariant to attentional focus. A main effect of attentional focus was found in dorsal frontoparietal cortices, whose activity signaled task-relevant target events irrespective of emotional content. The only brain region that was sensitive to both emotion and attentional focus was the anterior cingulate gyrus (ACG). When circles were task-relevant, the ACG responded equally to circle targets and distracting emotional scenes. The ACG response to emotional scenes increased when they were task-relevant, and the response to circles concomitantly decreased. These findings support and extend prominent network theories of emotion-attention interactions that highlight the integrative role played by the anterior cingulate.

Saccade reward signals in posterior cingulate cortex.

Movement selection depends on the outcome of prior behavior. Posterior cingulate cortex (CGp) is strongly connected with both limbic and oculomotor circuitry, and CGp neurons respond following saccades, suggesting a role in signaling the motivational outcome of gaze shifts. To test this hypothesis, single CGp neurons were studied in monkeys while they shifted gaze to visual targets for liquid rewards that varied in size or were delivered probabilistically. CGp neurons responded following saccades as well as following reward delivery, and these responses were correlated with reward size. CGp neurons also responded following the omission of predicted rewards. The timing of CGp activation and its modulation by reward could provide signals useful for updating representations of expected saccade value.