Effect of Vagus Nerve Stimulation on Attention and Working Memory in Neuropsychiatric Disorders: A Systematic Review.

BACKGROUND: It has been suggested that vagus nerve stimulation (VNS) may enhance attention and working memory. The neuromodulator effects of VNS are thought to activate the release of neurotransmitters involving cognition and to promote neuronal plasticity. Therefore, VNS has been studied for its effects on attention and working memory impairment in neuropsychiatric disorders. OBJECTIVES: This study aimed to assess the effects of VNS on attention and working memory among patients with neuropsychiatric disorders, examine stimulation parameters, provide mechanistic hypotheses, and propose future studies using VNS. MATERIALS AND METHODS: We conducted a systematic review using electronic databases MEDLINE (Ovid), Embase (Ovid), Cochrane library, and PsycINFO (Ovid). Narrative analysis was used to describe the therapeutic effects of VNS on attention and working memory, describe stimulation parameters, and propose explanatory mechanisms. RESULTS: We identified 20 studies reporting VNS effects on attention and working memory in patients with epilepsy or mood disorders. For epilepsy, there was one randomized controlled trial from all 18 studies. It demonstrated no statistically significant differences in the cognitive tasks between active and control VNS. From a within-subject experimental design, significant improvement of working memory after VNS was demonstrated. One of three nonrandomized controlled trials found significantly improved attentional performance after VNS. The cohort studies compared VNS and surgery and found attentional improvement in both groups. Nine of 12 pretest-posttest studies showed improvement of attention or working memory after VNS. For mood disorders, although one study showed significant improvement of attention following VNS, the other did not. CONCLUSIONS: This review suggests that, although we identified some positive results from eligible studies, there is insufficient good-quality evidence to establish VNS as an effective intervention to enhance attention and working memory in persons with neuropsychiatric disorders. Further studies assessing the efficacy of such intervention are needed.

Receptor for Advanced Glycation End Products (RAGE) Mediates Cognitive Impairment Triggered by Pneumococcal Meningitis.

Pneumococcal meningitis is a life-threatening infection of the central nervous system (CNS), and half of the survivors of meningitis suffer from neurological sequelae. We hypothesized that pneumococcal meningitis causes CNS inflammation via the disruption of the blood-brain barrier (BBB) and by increasing the receptor for advanced glycation end product (RAGE) expression in the brain, which causes glial cell activation, leading to cognitive impairment. To test our hypothesis, 60-day-old Wistar rats were subjected to meningitis by receiving an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a control group and were treated with a RAGE-specific inhibitor (FPS-ZM1) in saline. The rats also received ceftriaxone 100 mg/kg intraperitoneally, bid, and fluid replacements. Experimental pneumococcal meningitis triggered BBB disruption after meningitis induction, and FPS-ZM1 treatment significantly suppressed BBB disruption. Ten days after meningitis induction, surviving animals were free from infection, but they presented increased levels of TNF-α and IL-1ß in the prefrontal cortex (PFC); high expression levels of RAGE, amyloid-ß (Aß1-42), and microglial cell activation in the PFC and hippocampus; and memory impairment, as evaluated by the open-field, novel object recognition task and Morris water maze behavioral tasks. Targeted RAGE inhibition was able to reduce cytokine levels, decrease the expression of RAGE and Aß1-42, inhibit microglial cell activation, and improve cognitive deficits in meningitis survivor rats. The sequence of events generated by pneumococcal meningitis can persist long after recovery, triggering neurocognitive decline; however, RAGE blocker attenuated the development of brain inflammation and cognitive impairment in experimental meningitis.