Selective attention from voluntary control of neurons in prefrontal cortex

Abstract

Animals can learn to voluntarily control neuronal activity within various brain areas through operant conditioning, but the relevance of that control to cognitive functions is unknown. We found that rhesus monkeys can control the activity of neurons within the frontal eye field (FEF), an oculomotor area of the prefrontal cortex. However, operantly driven FEF activity was primarily associated with selective visual attention, and not oculomotor preparation. Attentional effects were untrained and were observed both behaviorally and neurophysiologically. Furthermore, selective attention correlated with voluntary, but not spontaneous, fluctuations in FEF activity. Our results reveal a specific association of voluntarily driven neuronal activity with "top-down" attention and suggest a basis for the use of neurofeedback training to treat disorders of attention.

Fig. 1

Operant control paradigm. (A) Location of the FEF in the arcuate sulcus (shading) shown in a lateral view of a monkey brain (top). Eye traces at bottom-left show saccades evoked with 50μA microstimulation of an FEF site. Bottom-middle and right show saccadic and visual responses, respectively, at the same FEF site during a visually guided delayed saccade task. (B) Operant control task. The monkey fixated a central spot on an otherwise blank video display. Dotted circle shows the FEF RF, speaker icon and musical notes depict auditory feedback of FEF neuronal activity (spike train) during a sliding 500 ms window (open rectangle). (C) Spike counts and rewards. Histograms show binned spike counts during Up and Down operant control for the example site in A. Rewards (blue droplets) were delivered each time a spike count reached the high threshold (red dotted line) on Up trials, or the low threshold (blue dotted line) on Down trials.

Fig. 2

Voluntary control of FEF neurons. (A) Average MUA over the course of Up (red) and Down (blue) trials during an example experiment. (B) Firing rates for each Down and Up trial in A are indicated by blue and red triangles, respectively, with the mean firing rate for a block of trials represented by a horizontal line. Gray vertical bars mark the first ten trials after each block transition, which were excluded from analysis. (C) Time course of the control index for the experiment in A. (D) Population histogram of multiunit CIs. Light gray histogram shows all experiments, purple histogram shows experiments with individually significant positive control, and dark gray histogram shows experiments with significant negative control. Inset shows the mean time course of voluntary control (colors as in the histogram). Thickness of each envelope is ± s.e.m. (E) The control index of single FEF neurons as a function of their visual (left) and saccadic response indices (right). (F) Population histograms showing Up-Down differences in LFP power in four frequency bands. * = significant difference at P < 0.05, *** is P < 0.001.

Fig. 3

Behavioral and physiological consequences of operant FEF control. (A) Visual search probe trials, in which a search array appeared and the monkey was rewarded (blue droplet) for directing a saccade toward an oriented bar target. (B) Percentage of probe trials in which a saccade was directed into the RF, correctly or incorrectly during all conditions (ellipsis), and during Up (red) and Down (blue) operant control. Purple triangles: Monkey B; purple squares: Monkey C. (C) Proportion of target misses in the RF. (D) Proportion of target misses opposite the RF. (E) FEF responses to the visual search array. The normalized population response of 150 FEF neurons aligned to array onset for trials with the target in the RF (black) or opposite the RF (gray). Gray bar along abscissa indicates the interval during which the target and distracter responses were significantly different. (F) FEF responses to targets in the RF on Up and Down trials. Data are the same as the black line in E, but red and blue lines show responses on Up and Down trials, respectively. (G) FEF responses to distracters in the RF, when the target was opposite. Data are the same as the gray line in E. (H) Target discrimination by FEF neurons, defined as the difference in responses between “Target in RF” and “Target opposite” trials. Bar plot shows mean target discrimination on Up (red) and Down (blue) trials. ** = significant difference at P < 0.01.

Fig. 4

Correlation of spontaneous activity with FEF responses. (A) Linear regression between the probe trial response of an example FEF neuron and its spontaneous pre-probe activity during Up (red) and Down (blue) control. (B and C) Population histogram of regression coefficients describing the relationship between spontaneous activity and responses to targets (B) or distracters (C) in the RF. Arrows denote medians of each distribution. * = significant difference at P < 0.05, ** is P < 0.01.