Working Memory Gates Visual Input to Primate Prefrontal Neurons

  1. Behrad Noudoost
  2. Kelsey L. Clark
  3. Tirin Moore

  • Curated by eLife

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    Summary:

    This is a brief paper documenting the properties of neurons in the frontal eye field (FEF), a cortical brain area traditionally thought to receive visual input and transform it internally to motor commands. The authors used extracellular recordings and electrical microstimulation in behaving non-human primates to add to this view by showing that visual input to FEF from visual area V4 appears to be gated by working -memory activity in FEF. The study was considered well done and interesting, albeit with several important concerns about the interpretation of the findings.

    Reviewer #1 opted to reveal their name to the authors in the decision letter after review.

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Abstract

Visually guided behavior relies on the integration of sensory input with information held in working memory. Yet it remains unclear how this is accomplished at the level of neural circuits. We studied the direct visual cortical inputs to neurons within a visuomotor area of prefrontal cortex in behaving monkeys. We show that the synaptic efficacy of visual cortical input to prefrontal cortex is gated by information held in working memory. Surprisingly, visual input to prefrontal neurons was found to target those with both visual and motor properties, rather than preferentially targeting other visual neurons. Furthermore, activity evoked from visual cortex was larger in magnitude, more synchronous, and more rapid, when monkeys remembered locations that matched the location of visual input. These results indicate that working memory directly influences the circuitry that transforms visual input into visually guided behavior.

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  1. eLife

    Reviewer #2:

    This is a very interesting study, examining the properties of different types of neurons in the primate Frontal Eye Fields. It is commonly assumed that a serial processing of information takes place in the frontal lobe, from visual representation, to working memory maintenance, to motor output. However, some evidence to the contrary has also been reported, creating a debate in the field. The authors have characterized meticulously FEF neurons receiving V4 projections, by means of orthodromic stimulation. They report two main findings: that visual-input recipient neurons in FEF exhibit substantial motor activity and that working memory alters the efficacy of V4 input to FEF. The paper provides an important addition to our understanding of FEF processing. Although the first result is unambiguous, and goes against the traditional view of the FEF, the interpretation of the second is less straightforward and would need to be qualified further.

    1. Orthodromic activation of FEF neurons via V4 stimulation increases the percentage of FEF events that lead to spikes and decreases their latency during working memory. Such an effect appears expectable if FEF neurons are at a higher level when a stimulus in their receptive field is held in memory compared to a stimulus out of their receptive field. Are the authors suggesting something special about working memory? Would the same outcome not be expected during fixation or smooth pursuit for FEF neurons that are activated by these states? It was not clear that the efficacy of transmission itself improves by working memory, just the likelihood that the spiking threshold would be reached.

    2. It would strengthen the author's thesis to discuss the existing functional evidence (in addition to anatomical evidence) that motor FEF neurons receive visual input and can plan movements accordingly. See for example Costello et al. J. Neurosci 2013, 33(41):16394-408.

    3. The authors match the receptive location of FEF and V4 neurons to maximize the chances of identifying monosynaptically connected neurons between the two areas. However, a negative finding of ia orthodromic activation does not entirely rule out that the FEF neuron under study receives V4 input, from another site. Some discussion is warranted on this point.

  2. eLife

    Reviewer #1:

    The authors of Working Memory Gates Visual Input to Primate Prefrontal Neurons studied how working memory influences information transmitting from V4 to frontal eye field via extracellular recording and electrical stimulation on behaving primate. They found that V4 neurons target FEF neurons with both visual and motor properties, and its synaptic efficacy of V4 to FEF was enhanced by working memory. These findings are interesting and important to our understanding about how our brain acts during daily WM-related activity.

    1. In classical working memory tasks, the task periods usually consist of fixation, cue, delay and then a response period. The neural activity during the delay period is typically considered to be a working memory-related signal. However, in the current study, the authors didn't point out whether only delay period activity was included in analysis when they compared synaptic efficacy between stimulation and non-stimulation trials, in Figure 4a. Because the differences of neuronal response during fixation period cannot be viewed as relevant to information held in working memory, it may be better if only neuronal activity in the delay period was included in their analysis.

    2. Did the 96 visual-recipient FEF neurons exhibit working memory-related activity in their memory guided saccade task? The example neuron in Figure 3a didn't show significant difference between In and Out trials during the delay period. If the visual-recipient neuron didn't present working memory related activity, how could the authors say enhanced synaptic efficacy from V4 to FEF was caused by working memory?

    3. Did the two example neurons in Figure 4c show adjusted values (subtracting the same measure during non-stimulated trials)? The authors mentioned in Method that Figure 4 showed adjusted values, but it may not be applicable for raster plot in Figure 4c. It may be helpful that using adjusted values show stimulation effects on evoked spike counts during memory In and Out trials.

    4. Did the authors find some FEF cells showing elevated firing during delay period in outside-RF trials compared with baseline firing? These elevated firing was not caused by RF cue, may underlying working memory signal.

    5. The sample size should be indicated in Figure 3b Venn diagram.

    6. It's better to indicate electrical stimulus protocol in Figure 1.

  3. eLife

    Summary:

    This is a brief paper documenting the properties of neurons in the frontal eye field (FEF), a cortical brain area traditionally thought to receive visual input and transform it internally to motor commands. The authors used extracellular recordings and electrical microstimulation in behaving non-human primates to add to this view by showing that visual input to FEF from visual area V4 appears to be gated by working -memory activity in FEF. The study was considered well done and interesting, albeit with several important concerns about the interpretation of the findings.

    Reviewer #1 opted to reveal their name to the authors in the decision letter after review.

  4. Version published to 10.1101/2020.11.09.375287 on bioRxiv