Visual plasticity declines sharply after the critical period, yet we easily learn to recognize new faces and places, even as adults. Such learning is often characterized by a "moment of insight,'' an abrupt and dramatic improvement in recognition. The mechanisms that support abrupt learning are unknown, but one hypothesis is that they involve changes in synchronization between brain regions. To test this hypothesis, we used a behavioral task in which non-human primates rapidly learned to recognize novel images and to associate them with specific responses. Simultaneous recordings from inferotemporal and prefrontal cortices revealed a transient synchronization of neural activity between these areas that peaked around the moment of insight. Synchronization was strongest between inferotemporal sites that encoded images and reward-sensitive prefrontal sites. Moreover, its magnitude intensified gradually over image exposures, suggesting that abrupt learning is the culmination of a search for informative signals within a circuit linking sensory information to task demands.

Visual cortical plasticity declines sharply after the critical period, and yet we easily learn to recognize new faces and places throughout our lives. Such learning is often characterized by a “moment of insight”, an abrupt and dramatic improvement in recognition. We studied the brain mechanisms that support this kind of learning, using a behavioral task in which non-human primates rapidly learned to recognize visual images and to associate them with particular responses. Simultaneous recordings from the inferotemporal and prefrontal cortices revealed a transient synchronization of neural activity between these two areas that peaked around the moment of insight. This synchronization was strongest between inferotemporal sites that encoded images and prefrontal sites that encoded rewards. Moreover, its magnitude built up gradually with successive image exposures, suggesting that abrupt learning is the culmination of a search for informative visual signals within a circuit that links sensory information to task demands.

Spike timing is thought to play a critical role in neural computation and communication. Methods for adjusting spike timing are therefore of great interest to researchers and clinicians alike. Transcranial electrical stimulation (tES) is a noninvasive technique that uses weak electric fields to manipulate brain activity. Early results have suggested that this technique can improve subjects' behavioral performance on a wide range of tasks and ameliorate some clinical conditions. Nevertheless, considerable skepticism remains about its efficacy, especially because the electric fields reaching the brain during tES are small, whereas the likelihood of indirect effects is large. Our understanding of its effects in humans is largely based on extrapolations from simple model systems and indirect measures of neural activity. As a result, fundamental questions remain about whether and how tES can influence neuronal activity in the human brain. Here, we demonstrate that tES, as typically applied to humans, affects the firing patterns of individual neurons in alert nonhuman primates, which are the best available animal model for the human brain. Specifically, tES consistently influences the timing, but not the rate, of spiking activity within the targeted brain region. Such effects are frequency- and location-specific and can reach deep brain structures; control experiments show that they cannot be explained by sensory stimulation or other indirect influences. These data thus provide a strong mechanistic rationale for the use of tES in humans and will help guide the development of future tES applications.

Khatoun et al. (1) are concerned that our paper (2) did not “establish the field strength required for tACS [transcranial alternating current stimulation] to cause neural entrainment.” This is true, but in our defense there is no evidence that any such threshold exists: The effects of electric fields on neuronal membrane potentials have been shown to be continuous and linearly related to the electric field strength (3, 4); a similar dose–response relationship is seen in the spiking output (5). Nevertheless, the issue of a minimum field strength forms the basis for Khatoun et al.’s (1) comment. The specific concern Khatoun et al. (1 … [↵][1]2To whom correspondence may be addressed. Email: christopher.pack{at}mcgill.ca. [1]: #xref-corresp-1-1

There has been growing interest in transcranial direct current stimulation (tDCS), a non-invasive technique purported to modulate neural activity via weak, externally applied electric fields. Although some promising preliminary data have been reported for applications ranging from stroke rehabilitation to cognitive enhancement, little is known about how tDCS affects the human brain, and some studies have concluded that it may have no effect at all. Here, we describe a macaque model of tDCS that allows us to simultaneously examine the effects of tDCS on brain activity and behavior. We find that applying tDCS to right prefrontal cortex improves monkeys' performance on an associative learning task. While firing rates do not change within the targeted area, tDCS does induce large low-frequency oscillations in the underlying tissue. These oscillations alter functional connectivity, both locally and between distant brain areas, and these long-range changes correlate with tDCS's effects on behavior. Together, these results are consistent with the idea that tDCS leads to widespread changes in brain activity and suggest that it may be a valuable method for cheaply and non-invasively altering functional connectivity in humans.