Boosting Learning Efficacy with Noninvasive Brain Stimulation in Intact and Brain-Damaged Humans

Abstract

Numerous behavioral studies have shown that visual function can improve with training, although perceptual refinements generally require weeks to months of training to attain. This, along with questions about long-term retention of learning, limits practical and clinical applications of many such paradigms. Here, we show for the first time in female and male human participants that just 10 d of visual training coupled with transcranial random noise stimulation (tRNS) over visual areas causes dramatic improvements in visual motion perception. Relative to control conditions and anodal stimulation, tRNS-enhanced learning was at least twice as fast, and, crucially, it persisted for 6 months after the end of training and stimulation. Notably, tRNS also boosted learning in patients with chronic cortical blindness, leading to recovery of motion processing in the blind field after just 10 d of training, a period too short to elicit enhancements with training alone. In sum, our results reveal a remarkable enhancement of the capacity for long-lasting plastic and restorative changes when a neuromodulatory intervention is coupled with visual training.SIGNIFICANCE STATEMENT Our work demonstrates that visual training coupled with brain stimulation can dramatically reduce the training period from months to weeks, and lead to fast improvement in neurotypical subjects and chronic cortically blind patients, indicating the potential of our procedure to help restore damaged visual abilities for currently untreatable visual dysfunctions. Together, these results indicate the critical role of early visual areas in perceptual learning and reveal its capacity for long-lasting plastic changes promoted by neuromodulatory intervention.

Keywords: cortical plasticity; noninvasive brain stimulation; perceptual learning; stroke recovery; tRNS; visual areas.

Copyright © 2019 the authors.

Figures

Figure 1.

Experimental procedure and behavioral task. A, All participants were tested on a motion integration task to determine baseline performance in the first session (day 1). They then underwent 9 d of training with or without on-line brain stimulation (days 2–10). Behavioral testing was performed again 6 months after the end of training/stimulation (post-6 month follow-up). B, Example of stimuli with different direction ranges (0°, 90°, and 360°) used for the motion integration task; target dots were embedded in noise dots that are not shown in the figure for clarity purposes (for details, see Materials and Methods). NDR = 0 (for details, see text) indicates fully random motion directions (360° range), while NDR = 100 indicates all signal dots moving in one direction (0° range). A two-alternative forced-choice, adaptive staircase procedure was used to estimate the largest range of dot directions that subjects could correctly integrate to discriminate the global motion direction (leftward vs rightward). C, Trial sequence used for training and to measure left–right motion discrimination thresholds. First, subjects were asked to fixate the central cross for 1000 ms, immediately followed by a tone signaling the appearance of the stimulus, which was presented for 500 ms. Subjects had to indicate the perceived global motion direction by pressing the left or right arrow key on the keyboard.

Figure 2.

Example psychometric data fits. Here, we selected the tRNS subject whose data were closest to the average of all nine tRNS subjects (going from 94% NDR to 30% NDR over 10 sessions). For each session (1–10), blue symbols show all individual trial data (correct trials are at the top and incorrect trials are the bottom of each panel). Psychometric function fits are shown by the red lines. For illustration purposes, individual trials are binned into 10 30-trial bins (red circles).

Figure 3.

Neuroradiological images and visual perimetries of CB patients. All patients sustained damage of early visual areas or the optic radiations, resulting in homonymous visual field defects as shown by the visual field perimetries, next to each brain image. Within the perimetry images (patients in top two rows: Sham1, Sham2, RNS1, RNS2, and RNS3): red marks and shading areas indicate the patients' blind field. Bottom two rows: Humphrey visual field maps for each of the unstimulated patient (U1–6), with superimposed shading indicating the blind field and numbers indicating the luminance detection sensitivity in the given position expressed in decibels. For all patients, the blue circles indicate the training location and size (for details, see Global direction discrimination testing and training in patients, in Materials and Methods). Radiological images were not available for patients RNS3 and U6.

Figure 4.

Effects of brain stimulation on perceptual learning in visually intact subjects. A, NDR thresholds for the control groups, tRNS group, and a-tDCS group. Dashed lines are linear fits, indicating the learning slope. B, Same data as in A, but expressed as the percentage improvement relative to day 1 thresholds. C, Learning index computed in three different ways. The tRNS group exhibited a significantly stronger amount of learning (day 1 − day 10; F(2,42) = 9.39, p = 0.0004; all Tukey's HSD, p < 0.002), percentage improvement (100 * (day 1 − day 10)/day 1; F(2,42) = 10.8, p = 0.00016; all Tukey's HSD, p < 0.001), and learning slope (F(2,42) = 7.8, p = 0.001; all Tukey's HSD, p < 0.008) than both the control and a-tDCS groups. D, Amount of learning, defined as the difference from day 1 thresholds, at the end of the training (left) and 6 months after (right). Error bars are ±1 SEM.

Figure 5.

The effects of brain stimulation on perceptual learning in patients with CB. A–C, Task performance over 10 training days for patients who underwent sham stimulation (A), those who received tRNS (B), and six unstimulated patients (C). The raw percentage of correct performance was normalized by subtracting the average percentage correct for the first 2 training days. D, Comparison of the raw percentage correct averaged over the first 2 d against the raw percentage correct for the final 2 training days. Significant learning was observed only for patients who trained with tRNS. All error bars indicate 95% confidence intervals. For A–C, all lines are linear fits, indicating the learning slope.