Transcranial Stimulation of the Dorsolateral Prefrontal Cortex Prevents Stress-Induced Working Memory Deficits

Abstract

Stress is known to impair working memory performance. This disruptive effect of stress on working memory has been linked to a decrease in the activity of the dorsolateral prefrontal cortex (dlPFC). In the present experiment, we tested whether transcranial direct current stimulation (tDCS) of the dlPFC can prevent stress-induced working memory impairments. We tested 120 healthy participants in a 2 d, sham-controlled, double-blind between-subjects design. Participants completed a test of their individual baseline working memory capacity on day 1. On day 2, participants were exposed to either a stressor or a control manipulation before they performed a visuospatial and a verbal working memory task. While participants completed the tasks, anodal, cathodal, or sham tDCS was applied over the right dlPFC. Stress impaired working memory performance in both tasks, albeit to a lesser extent in the verbal compared with the visuospatial working memory task. This stress-induced working memory impairment was prevented by anodal, but not sham or cathodal, stimulation of the dlPFC. Compared with sham or cathodal stimulation, anodal tDCS led to significantly better working memory performance in both tasks after stress. Our findings indicate a causal role of the dlPFC in working memory impairments after acute stress and point to anodal tDCS as a promising tool to reduce cognitive deficits related to working memory in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder.

Significance statement: Working memory deficits are prominent in stress-related mental disorders, such as depression, schizophrenia, or post-traumatic stress disorder. Similar working memory impairments have been observed in healthy individuals exposed to acute stress. So far, attempts to prevent such stress-induced working memory deficits focused mainly on pharmacological interventions. Here, we tested the idea that transcranial direct current stimulation of the dorsolateral prefrontal cortex (dlPFC), a critical neural substrate of working memory, may prevent working memory impairments after stress. Our results indicate that anodal stimulation of the dlPFC may indeed preserve working memory performance under stress, suggesting that the dlPFC plays a causal role in stress-induced working memory deficits and pointing to a potential new avenue to prevent stress-induced cognitive impairments.

Keywords: brain stimulation; dorsolateral prefrontal cortex; glucocorticoids; stress; working memory.

Figure 1.

Sympathetic nervous system responses to the TSST. Exposure to the TSST, but not to the control manipulation, led to significant increases in systolic blood pressure (A), diastolic blood pressure (B), and pulse (C). Stress and control groups differed in these parameters during the TSST/control manipulation and shortly thereafter but not before the TSST/control manipulation or before working memory testing started. Error bars indicate SEM. *p < 0.05. ***p < 0.001.

Figure 2.

Salivary cortisol responses to the TSST. Cortisol concentrations increased in response to the TSST but not in response to the control manipulation. Peak cortisol concentrations were reached shortly before working memory testing started. Error bars indicate SEM. **p < 0.01. ***p < 0.001.

Figure 3.

Anodal tDCS prevents stress-induced working memory impairments. A, Exposure to the TSST impaired Corsi block backwards performance, an indicator of visual-spatial working memory, in the sham and cathodal tDCS groups but not in the anodal tDCS group. B, Similarly, TSST exposure tended to reduce digit span backwards performance, an indicator of verbal working memory, in the sham and cathodal tDCS groups but not in the anodal tDCS group. In both tasks, working performance after stress was significantly better in participants that received anodal tDCS over the dlPFC than in those that received sham or cathodal stimulation. Error bars indicate SEM. *p < 0.05. **p < 0.01.