Table 2.
Impact of transcranial direct current stimulation on memory and learning in animal models of brain disorders.
| Author | Year | Animal model | Specimen; gender | N | Stimulation parameters | Main findings | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stimulation electrode | Reference electrode | Anesthesia | rtDCS | ||||||||||||
| Polarity | Position | Stimulation intensity (mA) | Size (cm2) | Stimulation duration (min) | Current density (A/m2) | Position | Area (cm2) | ||||||||
| Kamida et al. [32] | 2011 | Lithium-pilocarpine hydrochloride (60 mg/kg) SC injection at P20-21 | Wistar rats; males | 18 | c-tDCS | Hippocampus | 0.2 | 0.035 | 30 | N/A | Back of neck | N/A | N | Y (daily for 2 weeks) | ↓ SE-induced hippocampal cell loss in CA3 region |
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| Yu et al. [43] | 2014 | Scopolamine IP injection | Sprague Dawley rats; both genders | 16 | N/A | Parietal cortex (hippocampus) | 0.1 | N/A | 20 | N/A | N/A | N/A | N/A | Y (2x/day during 5 days a week, for 4 weeks) | ↓ Time and ↓ number of errors to reach food pellets Significant differences in ACh content (day 14 and day 28) ↑ Motor function |
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| Pedron et al. [49] | 2014 | Nicotine IP injection (1 mh/kg 2x/day for 14 days) | Swiss mice; females | 152 | a-tDCS | Left frontal cortex | 0.2 | 0.035 | 2 × 20 | N/A | Ventral thorax | 9.5 | N | Y (5 days) | ↑ Working memory |
| ↑ Nicotine-induced place preference conditioning (3 weeks poststimulation) | |||||||||||||||
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| Yu et al. [30] | 2015 | Bilateral hippocampus Aβ1-40 injection | Sprague Dawley rats; females | 36 | a-tDCS | Right frontal cortex | 0.02; 0.06; 0.1; 0.2 | 0.0314 | 20 | N/A | Ventral thorax | 10 | N | Y (10 sessions in 2 weeks) | ↑ Spatial learning performance (best with 0.1 mA and 0.2 mA stimulation) |
| ↓ GFAP expression in CA1 hippocampus region and DG (best with 0.1 mA stimulation) | |||||||||||||||
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| Yoon et al. [31] | 2016 | Lateral fluid percussion method | Sprague Dawley rats; males | 36 | a-tDCS | Hippocampus | 0.2 | 0.0225 | 20 | 28.2 | Chest | 48 (corset) | Y | Y (daily for 5 days) | ↑ Perilesional area BDNF expression (tDCS 2 weeks post-TBI) ↑ Choline/creatinine ratios (tDCS 1 week post-TBI) Motor performance recovery (2 weeks of tDCS) |
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| Leffa et al. [33] | 2016 | SHR | SHR rats and WKT rats; males | 48 | a-tDCS | Frontal cortex | 0.5 | 1.5 | 20 | 33.4 | Between ears | 1.5 | N | Y (8 consecutive days) | ↑ DA levels in STR in both rat strains and in the hippocampus following tDCS treatment in WKY ↑ BDNF levels in WKY rats Short-term memory improvement |
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| Wu et al. [45] | 2017 | STZ-induced diabetic rats | Sprague Dawley rats; males | 130 | a-tDCS | dPFC | 0.2 | 0.0314 | 30 | N/A | Anterior chest | 0.25 | Y | Y | ↑ Spatial working memory and mPFC LTP restoring |
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| Pedron et al. [50] | 2017 | Cocaine injections | Swiss mice; females | 165 | a-tDCS | Left frontal cortex | 0.2 | 0.035 | 2 × 20 | N/A | Ventral thorax | 9.5 | N | Y (5 days stimulation, twice a day; 5 h interstimulation interval) | ↓ Cocaine-induced locomotor activity No cocaine-induced place preference (5 mg/kg and 25 mg/kg) ↑ Zif268 basal expression under the electrode area, in the STR and cortex |
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| Leffa et al. [55] | 2018 | ADHD | SHR and WKY rats; males | 30 | a-tDCS (bicephalic) | Frontal cortex (supraorbital area) | 0.5 | 1.5 (ECG electrode) | 20 | 33.3 | Neck | 1.5 (ECG electrode) | N/A | Y (8 days) | ↓ Inflammatory cytokines and reversion of long-term memory deficits in SHR rats |
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| Bragina et al. [47] | 2018 | CCI | Mice; N/A | 40 | a-tDCS | Parietal somatosensory cortex | 0.1 | N/A | 15 | N/A | Ventral thorax | N/A | N/A | Y (daily for 4 days, over 4 weeks and 3 days interval) | Motor coordination recovery Spatial memory and learning performance improvement ↑ CBF bilaterally (regional arteriolar dilatation and hypoxia reduction) |
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| Roostaei et al. [44] | 2019 | STZ-induced diabetic rats | Wistar rats; males | 64 | a-tDCS vs. c-tDCS | Left frontal cortex | 0.2 | 3.5 | 20 | N/A | Ventral thorax | 9.5 | N | Y (twice a day over 2 days) | Restoration of STZ-induced amnesia (both polarities) |
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| Gondard et al. [55] | 2019 | Animal model of AD-triple transgenic (3xTg) mice | Triple transgenic (3xTg) mice; males | 27 | c-tDCS and a-tDCS | Secondary motor cortex (m2) (c-TDCS) and dorsal temporal hippocampus (a-tDCS) | 0.05 | 0.0325 | 20 | N/A | N/A | 0.0325 | N/A | Y (5 days/week for 3 weeks) | No treatment effect on memory outcome or AD neuropathological biomarkers |
Abbreviations: rtDCS: repetitive transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; c-tDCS: cathodal transcranial direct current stimulation; TBI: traumatic brain injury; ADHD: attention deficit hyperactivity disorder; SHR: spontaneous hypertensive rats; WKY: Wistar Kyoto rats; CBF: cerebral blood flow; PFC: prefrontal cortex; mPFC: medial prefrontal cortex; dPFC: dorsolateral prefrontal cortex; DG: dentate gyrus; STR: striatum; M2: secondary motor cortex; ITC: inferotemporal cortex; CA3: cornu ammonis 3 region in the hippocampus, STZ: streptozotocin; AD: Alzheimer's disease; Aβ1-40: amyloid beta peptide 1–40; ACh: acetylcholine; BDNF: brain-derived neurotrophic factor; DA: dopamine; GFAP glial fibrillary acidic protein; Zif268: zinc finger transcription factor 268; LTP: long-term potentiation; IP: intraperitoneal; SC: subcutaneous; SE: status epilepticus; ECG: electrocardiography; mg: milligram; kg: kilogram; A/m2: ampere per square meter; mA: milliampere; cm2: square centimeter; mm: millimeter; h: hour; min: minute; vs.: versus; Y: yes; N: no; N/A: not available.