Cognitive Training and Transcranial Direct Current Stimulation in Mild Cognitive Impairment: A Randomized Pilot Trial

Abstract

Background Transcranial direct current stimulation (tDCS), a non-invasive stimulation, represents a potential intervention to enhance cognition across clinical populations including Alzheimer’s disease and mild cognitive impairment (MCI). This randomized clinical trial in MCI investigated the effects of anodal tDCS (a-tDCS) delivered to left inferior frontal gyrus (IFG) combined with gist-reasoning training (SMART) versus sham tDCS (s-tDCS) plus SMART on measures of cognitive and neural changes in resting cerebral blood flow (rCBF). We were also interested in SMART effects on cognitive performance regardless of the tDCS group. Methods Twenty-two MCI participants, who completed the baseline cognitive assessment (T1), were randomized into one of two groups: a-tDCS + SMART and s-tDCS + SMART. Of which, 20 participants completed resting pCASL MRI scan to measure rCBF. Eight SMART sessions were administered over 4 weeks with a-tDCS or s-tDCS stimulation for 20 min before each session. Participants were assessed immediately (T2) and 3-months after training (T3). Results Significant group × time interactions showed cognitive gains at T2 in executive function (EF) measure of inhibition [DKEFS- Color word ( p = 0.047)], innovation [TOSL ( p = 0.01)] and on episodic memory [TOSL ( p = 0.048)] in s-tDCS + SMART but not in a-tDCS + SMART group. Nonetheless, the gains did not persist for 3 months (T3) after the training. A voxel-based analysis showed significant increase in regional rCBF in the right middle frontal cortex (MFC) (cluster-wise p = 0.05, k = 1,168 mm 3 ) in a-tDCS + SMART compared to s-tDCS + SMART. No significant relationship was observed between the increased CBF with cognition. Irrespective of group, the combined MCI showed gains at T2 in EF of conceptual reasoning [DKEFS card sort ( p = 0.033)] and category fluency [COWAT ( p = 0.055)], along with gains at T3 in EF of verbal fluency [COWAT ( p = 0.009)]. Conclusion One intriguing finding is a-tDCS to left IFG plus SMART increased blood flow to right MFC, however, the stimulation seemingly blocked cognitive benefits of SMART on EF (inhibition and innovation) and episodic memory compared to s-tDCS + SMART group. Although the sample size is small, this paper contributes to growing evidence that cognitive training provides a way to significantly enhance cognitive performance in adults showing memory loss, where the role of a-tDCS in augmenting these effects need further study.

Impact of 3-Day Combined Anodal Transcranial Direct Current Stimulation-Visuospatial Training on Object-Location Memory in Healthy Older Adults and Patients with Mild Cognitive Impairment

“…Mean improvement did not persist on follow-up, also in line with our findings. At odds with our results, Das et al, using a pre-training stimulation approach, showed a negative impact on immediate cognitive performance [46]. Note, though that optimal timing of tDCS application (pre-, during, or post-training) is still an open question and certainly depends on a number of factors, like task, current brain state, or population under study.…”

“…Thus, MCI patients, in whom low memory performance is a hallmark of the clinical symptomatology, may be particularly susceptible to the beneficial effects of atDCS. Encouraging results have been reported for repeated atDCS in MCI due to AD [42,43] and atDCS combined with CT in MCI due to idiopathic Parkinson's disease [44,45], but a negative effect has been reported in a study applying atDCS before CT in MCI due to AD [46]. Conflicting results might result from heterogeneity between stimulation protocols, e.g., application of atDCS before versus during training [38,47].…”

Effects of Transcranial Direct Current Stimulation (tDCS) in the Normalization of Brain Activation in Patients with Neuropsychiatric Disorders: A Systematic Review of Neurophysiological and Neuroimaging Studies

“…A total of three studies investigated the effects of tDCS on neurodevelopmental disorders, with two on ADHD [ 53 , 54 ] and one on dyslexia [ 42 ]. Two studies investigated MCI [ 33 , 55 ]. The demographic details, tDCS protocols, clinical/behavioral outcomes, and brain-behavior relationship results are listed in Table 1 .…”

“…The remaining two studies reported between-group differences in changes in interhemispheric imbalance [ 35 ] and regional cerebral blood flow (rCBF) after active and sham tDCS, respectively. Kim et al [ 35 ] reported that bilateral stimulation significantly normalized the interhemispheric imbalance in the active anodal stimulation group when compared to sham-stimulated individuals, while Das et al [ 55 ] revealed an increase in rCBF in the right medial prefrontal cortex at rest after applying anodal stimulation over the left IFG.…”

Multi-Session Anodal Prefrontal Transcranial Direct Current Stimulation does not Improve Executive Functions among Older Adults

“…However, the rest of these intervention studies (Cotelli et al, 2014;Fazeli, Woods, Pope, Vance, & Ball, 2019;Fileccia et al, 2019;Huo et al, 2018;Khedr et al, 2014;Manor et al, 2018;Nilsson, Lebedev, Rydström, & Lövdén, 2017;Ownby & Acevedo, 2016) did not observe significant tDCS-associated gains in any EF tests administered in their studies. One study even reported significant EF gains in the sham stimulation group, but not the tDCS group (Das et al, 2019). It should be noted that these studies had relatively small sample sizes (N treatment group ≤ 21), apart from a few exceptions (N treatment group ≥ 30; Huo et al, 2018;Nilsson et al, 2017;Stephens & Berryhill, 2016).…”