Can neuromodulation alleviate cognitive deficits?

Since the Food and Drug Administration (FDA) approved Transcranial Magnetic Stimulation (TMS) for depression as a non-invasive brain stimulation approach in 2008, its application has revolutionized psychiatry.Recently, new indications such as Obsessive Compulsive Disorder (OCD), smoking cessation, and anxiety with comorbid Major Depressive Disorder (MDD) have been approved.Additionally, various methodological options have exponentially increased and significantly diverged across studies.Factors such as location, waveform, energy or generated electric field (EF), direction of the EF, frequency of sessions, total number of stimulations during treatment, and timing can all be varied even for the same indication.There are few restrictions on selecting parameters, and most are not evidence-based.For instance, many studies target the dorsolateral prefrontal cortex (DLPFC), but the rationale for this is often supported only by early imaging findings [1] which were not later replicated.Additionally, the frequency constraints and their purported inhibitory (low frequency) or excitatory (higher than 5 Hz) effects are based on motor evoked potential (MEP) measures, which exhibit small, noisy effects with significant inter-subject variability [2,3].The strength of stimulation is another aspect that is rarely consistently tested, often ranging from 80 % to 130 % across studies.The number of stimulations per session and the number of sessions in a day is also a hotly debated area, particularly due to the recent success of accelerated TMS protocols [4].While this variability can fertilize interventional psychiatry research, it also poses a challenge to obtaining stronger evidence for new interventions.Exploratory interventional studies are typically small and lack harmonization in their parameter space, making conclusive interpretations difficult.This is why the current review by Pagali et al.[5] is very crucial in evaluating whether TMS has an effect on cognition in general, and on Alzheimer's dementia (AD) in particular.The authors conducted a systematic review and synthesized data from 143 TMS studies on cognitive impairments in different groups.These studies included both randomized controlled trials (RCTs) and observational cohorts, with results overwhelmingly indicating positive outcomes in Mini Mental Commentary on "Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer's disease, Alzheimer's diseaserelated dementias, and other cognitive disorders: a systematic review and meta-analysis" by Pagali et al.