The autonomous sensory meridian response (ASMR) is a tingling sensation in the scalp, neck, and back caused by sensory stimuli triggering the parasympathetic response. With a wide genre of popular online videos created to induce ASMR, viewers have claimed benefits such as improved sleep and relaxation. This study investigates the potential of ASMR to revolutionize productivity, mood, and stress-management in a fast and affordable way. To do so, single-case experimental design was utilized, which turns an observational case report into a hypothesis tested under controlled conditions to highlight an individual’s distinct changes in state. Tests were administered over eight weeks to comprehensively quantify effects of ASMR on mental function, including assessments for mood, memory, and executive function; a smartwatch; and a wearable electroencephalography headset. This indicated gradual improvement in executive function (medium effect size) and long term memory (large effect size) across the testing period as well as immediate improvement of mood (medium effect size) and activation of the parasympathetic response following each intervention. Furthermore, wavelet transform analysis demonstrated statistically significant increase in the power of alpha and delta waves during intervention, which was supported by in silico validation via a convolutional neural network. This model can now be applied to detect the unique brain activity during ASMR stimulation on larger populations, making cognitive enhancement by novel biofeedback interventions time-efficient and globally accessible. Overall, this experiment is the first to demonstrate the physiological basis of ASMR’s potential to improve cognitive function, therefore encouraging a preventative approach to mental health care.