Optimizing the Effect of tDCS on Motor Sequence Learning in the Elderly.

One of the most visible effects of aging, even in healthy, normal aging, is a decline in motor performance. The range of strategies applicable to counteract this deterioration has increased. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that can promote neuroplasticity, has recently gained attention. However, knowledge about optimized tDCS parameters in the elderly is limited. Therefore, in this study, we investigated the effect of different anodal tDCS intensities on motor sequence learning in the elderly. Over the course of four sessions, 25 healthy older adults (over 65 years old) completed the Serial Reaction Time Task (SRTT) while receiving 1, 2, or 3 mA of anodal or sham stimulation over the primary motor cortex (M1). Additionally, 24 h after stimulation, motor memory consolidation was assessed. The results confirmed that motor sequence learning in all tDCS conditions was maintained the following day. While increased anodal stimulation intensity over M1 showed longer lasting excitability enhancement in the elderly in a prior study, the combination of higher intensity stimulation with an implicit motor learning task showed no significant effect. Future research should focus on the reason behind this lack of effect and probe alternative stimulation protocols.

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.

Dissociating the causal role of left and right dorsal premotor cortices in planning and executing bimanual movements - A neuro-navigated rTMS study.

BACKGROUND: The dorsal premotor cortex (PMd) is a key region in bimanual coordination. However, causal evidence linking PMd functionality during motor planning and execution to movement quality is lacking. OBJECTIVE: We investigated how left (PMdL) and right PMd (PMdR) are causally involved in planning and executing bimanual movements, using short-train repetitive transcranial magnetic stimulation (rTMS). Additionally, we explored to what extent the observed rTMS-induced modulation of performance could be explained by rTMS-induced modulation of PMd-M1 interhemispheric interactions (IHI). METHODS: Twenty healthy adults (mean age ± SD = 22.85 ± 3.73 years) participated in two sessions, in which either PMdL or PMdR was targeted with rTMS (10 Hz) in a pseudo-randomized design. PMd functionality was transiently modulated during the planning or execution of a complex bimanual task, whereby the participant was asked to track a moving dot by controlling two dials. The effect of rTMS on several performance measures was investigated. Concurrently, rTMS-induced modulation of PMd-M1 IHI was measured using a dual-coil paradigm, and associated with the rTMS-induced performance modulation. RESULTS: rTMS over PMdL during planning increased bilateral hand movement speed (p = 0.03), thereby improving movement accuracy (p = 0.02). In contrast, rTMS over PMdR during both planning and execution induced deterioration of movement stability (p = 0.04). rTMS-induced modulation of PMd-M1 IHI during planning did not predict rTMS-induced performance modulation. CONCLUSION: The current findings support the growing evidence on PMdL dominance during motor planning, as PMdL was crucially involved in planning the speed of each hand, subserving bimanual coordination accuracy. Moreover, the current results suggest that PMdR fulfills a role in continuous adjustment processes of movement.

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.

Preliminary Normative Data of Persian Phonemic and Semantic Verbal Fluency Test.

Objective: Verbal fluency tests (VFTs) are widely used in clinical practice and research to assess executive functions and are highly sensitive to frontal lobe lesions. However, using VFTs in different cultures and languages needs further considerations. The aim of this study was to provide a Persian (Farsi) version of verbal fluency with preliminary normative data. Method : In the first phase, 50 healthy native Persian-speaking individuals completed 1-minute VFT for all 32 letters in Persian to find letters with highest frequency. In the second phase, 100 healthy participants (50 females) were recruited into 5 age groups that were matched by gender and education. Participants were instructed to do 1-minute VFT for the 3 selected letters (phonemic VFT) and 3 categories (animal, supermarket, and fruit) (semantic VFT). For data analysis, one-way ANOVA was performed. Results: In the first phase, 3 letters (Pe standing for /P/, Meem for /M/ and Kaaf for /K/) had the highest frequency in word production (12 in average) and had been chosen for Persian phonemic VFT. Participants were assessed with the 3 selected letters (/P/: 12.28±3.607, /M/: 12.54±3.907, and /K/: 12.48±3.708) and 3 semantic categories (animal: 21.67±5.119, supermarket: 21.19±4.907, and fruit: 19.58±4.439) with 1-minute time limitation for each test. The results showed that education was significantly (p<0.01) associated with the performance in the phonemic but not semantic scores, while age was not correlated with either of the tests. No significant effect of gender was observed. Conclusion: Based on our results, we recommend Persian letters Pe, Meem, and Kaff that have the highest frequency in word production among others to be used for neuropsychological assessments and future studies in the Persian language. This is the same logic behind selecting F, A, and S in the English version. Although the norms obtained in this study are preliminary, these results can be useful in clinical evaluation with considerations about age and educational levels. Moreover, the findings of this study can be used as an initial step for more comprehensive normative studies.

The Persian Checklist of Pleasant Events (PCPE): Development, Validity and Reliability.

OBJECTIVE: Experiencing pleasant events during daily life has a significant positive role in the personal mental health and acts as a keystone for "behavioral activation" (BA) interventions. There are serious differences in the pleasant event schedules in different cultures and countries. We aimed to develop a Persian checklist of pleasant events (PCPE) to provide and validate a culturally compatible checklist for Iranians. METHODS: To develop a checklist of pleasant events, inspired by Pleasant Events Schedule (PES) (MacPhillamy & Lewinsohn, 1982), we held three focused group discussions with 24 normal healthy participants from both genders (female = 12) and asked them to mention as much pleasant events as possible. When the list reached saturation level, the inappropriate items with respect to legal, cultural and religious concerns were omitted. The final checklist of PCPE consists of two subscales: Frequency (frequency of events during last month) and pleasantness (perceived pleasantness of events). The total score consists of frequency multiplied by pleasantness. To test the reliability and validity of the checklist, the PCPE, Depression, Anxiety and Stress Scale (DASS), the Persian version of WHO Quality of Life and the Demographic Questionnaire were administered in a sample of 104 participants (50 male and 54 female). RESULTS: Frequency, pleasantness and the total scores of PCPE showed high levels of internal consistency (Cronbach's alpha, .976, .976 & .974, respectively). Further support for the convergent validity of the PCPE was obtained via moderate negative correlations with depression, anxiety, stress scores in DASS and positive correlation with quality of life as well as respondent's perceived happiness. There were negative correlations between frequency, pleasantness and total scores and age of the participants (Pearson correlation coefficient, r = -.194, p<0.05; r = -.270, p<0.01 & r = -.234, p<0.05, respectively). Conclusion : PCPE as an assessment tool has shown to have good reliability and validity among Iranians. Further steps should be taken to validate this instrument in different psychopathologies such as depression, addiction and obesity. .