Age-dependent non-linear neuroplastic effects of cathodal tDCS in the elderly population: a titration study.

BACKGROUND: Neuromodulatory effects of transcranial direct current stimulation (tDCS) in older humans have shown heterogeneous results, possibly due to sub-optimal stimulation protocols associated with limited knowledge about optimized stimulation parameters in this age group. We systematically explored the association between the stimulation dosage of cathodal tDCS and induced after-effects on motor cortex excitability in the elderly. METHOD: Thirty-nine healthy volunteers in two age groups, namely Pre-Elderly (50-65 years) and Elderly (66-80 years), participated in the study. Ten sessions of cathodal tDCS, with a combination of four intensities (1, 2, 3 mA and sham) and three durations (15, 20, 30 min) were conducted over the M1 in each participant. Cortical excitability changes were monitored with TMS-induced motor evoked potentials (MEPs) for up to 2 h after stimulation. RESULTS: Motor cortex excitability was reduced by cathodal stimulation intensities of 1 and 3 mA in both age groups, in accordance with results observed in the younger age groups of previous studies. For the 2 mA stimulation condition, an age-dependent conversion of plasticity into a stimulation duration-dependent excitability enhancement was observed in the Pre-Elderly group, whereas in the Elderly group, LTD-like plasticity was preserved, or abolished, depending on stimulation duration. CONCLUSION: The LTD-like plasticity effects induced by cathodal tDCS originally described in young adults are also observable in older humans, but non-linearities of the resulting plasticity were partially preserved only in the Pre-Elderly, but not the Elderly group. These results aid in understanding age-dependent plasticity dynamics in humans, and to define more efficient tDCS protocols in the aging brain.

Exploring and optimizing the neuroplastic effects of anodal transcranial direct current stimulation over the primary motor cortex of older humans.

BACKGROUND: tDCS modulates cortical plasticity and has shown potential to improve cognitive/motor functions in healthy young humans. However, age-related alterations of brain structure and functions might require an adaptation of tDCS-parameters to achieve a targeted plasticity effect in older humans and conclusions obtained from young adults might not be directly transferable to older adults. Thus, our study aimed to systematically explore the association between tDCS-parameters and induced aftereffects on motor cortical excitability to determine optimal stimulation protocols for older individuals, as well as to investigate age-related differences of motor cortex plasticity in two different age groups of older adults. METHODS: 32 healthy, volunteers from two different age groups of Young-Old (50-65 years, n = 16) and Old-Old (66-80 years, n = 16) participated in this study. Anodal tDCS was applied over the primary motor cortex, with respective combinations of three intensities (1, 2, and 3 mA) and durations (15, 20, and 30 min), in a sham-controlled cross-over design. Cortical excitability alterations were monitored by single-pulse TMS-induced MEPs until the next day morning after stimulation. RESULTS: All active stimulation conditions resulted in a significant enhancement of motor cortical excitability in both age groups. The facilitatory aftereffects of anodal tDCS did not significantly differ between age groups. We observed prolonged plasticity in the late-phase range for two protocols with the highest stimulation intensity (i.e., 3 mA-20 min, 3 mA-30 min). CONCLUSIONS: Our study highlights the role of stimulation dosage in tDCS-induced neuroplastic aftereffects in the motor cortex of healthy older adults and delivers crucial information about optimized tDCS protocols in the domain of the primary motor cortex. Our findings might set the grounds for the development of optimal stimulation protocols to reinstate neuroplasticity in different cortical areas and induce long-lasting, functionally relevant plasticity in normal aging and in pathological conditions, which would require however systematic tDCS titration studies over respective target areas.

Age-related differences of motor cortex plasticity in adults: A transcranial direct current stimulation study.

BACKGROUND: Cognitive, and motor performance are reduced in aging, especially with respect to acquisition of new knowledge, which is associated with a neural plasticity decline. Animal models show a reduction of long-term potentiation, but not long-term depression, in higher age. Findings in humans are more heterogeneous, with some studies showing respective deficits, but others not, or mixed results, for plasticity induced by non-invasive brain stimulation. One reason for these heterogeneous results might be the inclusion of different age ranges in these studies. In addition, a systematic detailed comparison of the age-dependency of neural plasticity in humans is lacking so far. OBJECTIVE: We aimed to explore age-dependent plasticity alterations in adults systematically by discerning between younger and older participants in our study. METHODS: We recruited three different age groups (Young: 18-30, Pre-Elderly: 50-65, and Elderly: 66-80 years). Anodal, cathodal, or sham transcranial direct current stimulation (tDCS) was applied over the primary motor cortex with 1 mA for 15 min to induce neuroplasticity. Cortical excitability was monitored by single-pulse transcranial magnetic stimulation as an index of plasticity. RESULTS: For anodal tDCS, the results show a significant excitability enhancement, as compared to sham stimulation, for both, Young and the Pre-Elderly groups, while no LTP-like plasticity was obtained in the Elderly group by the applied stimulation protocol. Cathodal tDCS induced significant excitability-diminishing plasticity in all age groups. CONCLUSION: Our study provides further insight in age-related differences of plasticity in healthy humans, which are similar to those obtained in animal models. The decline of LTP-like plasticity in higher age could contribute to cognitive deficits observed in aging.

Effects of electrode angle-orientation on the impact of transcranial direct current stimulation on motor cortex excitability.

BACKGROUND: For effects of transcranial direct current stimulation (tDCS), electrical field distribution and coverage of the target areas play a decisive role. METHODS: We explored the effect of different angle-orientations of tDCS electrodes applied over the upper limb motor cortex (M1) on motor cortex excitability in healthy volunteers. Sixteen individuals received 1 mA anodal or cathodal tDCS through 35 cm2 electrodes over M1 for 15 min. Transcranial magnetic stimulation was used to examine tDCS-generated cortical excitability effects. The M1 electrode-orientation was following the right-left longitudinal plane, or positioned with 45° deviation from the midsagittal plane. Coverage of underlying brain and electrical field orientation were also investigated. RESULTS: Cortical excitability modulation was observed only when the electrode was aligned with 45° angle, which covered a larger area of the motor cortex. CONCLUSION: an electrode angle-orientation of 45° induces superior neuroplastic effects of M1 due to a better alignment with the motor cortex.