Rationale:
Memory impairment is a complication of epilepsy, traumatic brain injury, and degenerative disorders like Alzheimer’s disease, with no established treatment options. Brain stimulation with electrical or magnetic signals represents a non-invasive and novel option with promising effects on cognition. To further explore this idea, we performed a meta-analysis summarizing the trends and results of several studies.
Methods:
We searched the keywords “non-invasive’, ‘stimulation’ and ‘memory” in Pubmed which resulted in 659 studies. We selected clinical trials and randomized controlled trials from January 2015 until January 2025, refining the results to 70 studies. Five studies without a clear description of results, duplicate studies, and studies outside the scope of analysis were removed. The type and duration of stimulation, target regions in the brain, duration of stimulation, details about sham stimulation, and alteration in memory parameters were analyzed.
Results:
65 studies were selected for analysis. The stimulation modalities included transcranial magnetic stimulation, transcranial direct current stimulation, intermittent theta burst stimulation, Slow-oscillatory transcranial direct current stimulation (sotDCS), transcranial infrared laser stimulation (TILS), Transcranial pulse stimulation (TPS), Cranial electrotherapy stimulation (CES), and Repetitive transcranial magnetic stimulation (rTMS). The stimulation targets were the precuneus, prefrontal cortex, motor cortex, and hippocampal networks.
72.31% (47/65) of studies with active stimulation compared to the 58.46% ( 38/65) sham showed improvement in memory parameters.
The cognitive domains and neuropsychology tests performed were intelligence (Wechsler Adult Intelligence Scale), cognitive flexibility (trail-making tests), Fugl-Meyer Assessment of the upper extremity (FMA-UE), depression (Beck Depression Inventory), attention (digital span), short term memory (Auditory Verbal Learning Test), Motor Evoked Potentials (MEPs) and anxiety (Beck Anxiety Inventory).
The duration of the stimulation varied from study to study. The mean age of the patients was 52 years. 47 studies showed improvement for active stimulation compared to the 38 sham. 21 studies showed no change for sham, and 13 studies showed no change for active stimulation. 3 studies for sham showed worsening, and 3 studies showed worsening for active stimulation. The parameters used were cognitive tests listed previously in the abstract: (Wechsler Adult Intelligence Scale), cognitive flexibility (trail-making tests), Fugl-Meyer Assessment of the upper extremity (FMA-UE), depression (Beck Depression Inventory), attention (digital span), short term memory (Auditory Verbal Learning Test), Motor Evoked Potentials (MEPs) and anxiety (Beck Anxiety Inventory).
Conclusions:
Non-invasive electrical and magnetic stimulation using a wide array of modalities, targets, and protocols improved memory and cognition compared to sham stimulation. Larger studies with standardized parameters comparing different stimulation modalities and brain targets will elucidate the effects of this novel therapeutic option.Funding:
None