Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.

Anodal tDCS applied during strength training enhances motor cortical plasticity

Purpose:
The objective of this study was to assess the effect of anodal transcranial direct current stimulation (a-tDCS) on voluntary dynamic strength and cortical plasticity when applied during a 3-wk strength training program for the wrist extensors.

Methods:
Thirty right-handed participants were randomly allocated to the tDCS, sham, or control group. The tDCS and sham group underwent 3 wk of heavy-load strength training of the right wrist extensors, with 20 min of a-tDCS (2 mA) or sham tDCS applied during training (double blinded). Outcome measures included voluntary dynamic wrist extension strength, muscle thickness, corticospinal excitability, short-interval intracortical inhibition (SICI), and silent period duration.

Results:
Maximal voluntary strength increased in both the tDCS and sham groups (14.89% and 11.17%, respectively, both P < 0.001). There was no difference in strength gain between the two groups (P = 0.229) and no change in muscle thickness (P = 0.15). The tDCS group demonstrated an increase in motor-evoked potential amplitude at 15%, 20%, and 25% above active motor threshold, which was accompanied by a decrease in SICI during 50% maximal voluntary isometric contraction and 20% maximal voluntary isometric contraction (all P < 0.05). Silent period decreased for both the tDCS and sham groups (P < 0.001).

Conclusion:
The application of a-tDCS in combination with strength training of the wrist extensors in a healthy population did not provide additional benefit for voluntary dynamic strength gains when compared with standard strength training. However, strength training with a-tDCS appears to differentially modulate cortical plasticity via increases in corticospinal excitability and decreases in SICI, which did not occur following strength training alone

Formation of cortical plasticity in older adults following tDCS and motor training

Neurodegeneration accompanies the process of natural aging, reducing the ability to perform functional daily activities. Transcranial direct current stimulation (tDCS) alters neuronal excitability and motor performance; however its beneficial effect on the induction of primary motor cortex (M1) plasticity in older adults is unclear. Moreover, little is known as to whether the tDCS electrode arrangement differentially affects M1 plasticity and motor performance in this population. In a double-blinded, cross-over trial, we compared unilateral, bilateral and sham tDCS combined with visuomotor tracking, on M1 plasticity and motor performance of the non-dominant upper limb, immediately post and 30 min following stimulation. We found (a) unilateral and bilateral tDCS decreased tracking error by 12–22% at both time points; with sham decreasing tracking error by 10% at 30 min only, (b) at both time points, motor evoked potentials (MEPs) were facilitated (38–54%) and short-interval intracortical inhibition was released (21–36%) for unilateral and bilateral conditions relative to sham, (c) there were no differences between unilateral and bilateral conditions for any measure. These findings suggest that tDCS modulated elements of M1 plasticity, which improved motor performance irrespective of the electrode arrangement. The results provide preliminary evidence indicating that tDCS is a safe non-invasive tool to preserve or improve neurological function and motor control in older adults.

Anodal-tDCS applied during unilateral strength training increases strength and corticospinal excitability in the untrained homologous muscle

Evidence suggests that the cross-transfer of strength following unilateral training may be modulated by increased corticospinal excitability of the ipsilateral primary motor cortex, due to cross-activation. Anodal-tDCS (a-tDCS) has been shown to acutely increase corticospinal excitability and motor performance, which may enhance this process. Therefore, we sought to examine changes in neural activation and strength of the untrained limb following the application of a-tDCS during a single unilateral strength training session. Ten participants underwent three conditions in a randomized, double-blinded crossover design: (1) strength training + a-tDCS, (2) strength training + sham-tDCS and (3) a-tDCS alone. a-tDCS was applied for 20 min at 2 mA over the right motor cortex. Unilateral strength training of the right wrist involved 4 × 6 wrist extensions at 70 % of maximum. Outcome measures included maximal voluntary strength, corticospinal excitability, short-interval intracortical inhibition, and cross-activation. We observed a significant increase in strength of the untrained wrist (5.27 %), a decrease in short-interval intracortical inhibition (−13.49 %), and an increase in cross-activation (15.71 %) when strength training was performed with a-tDCS, but not following strength training with sham-tDCS, or tDCS alone. Corticospinal excitability of the untrained wrist increased significantly following both strength training with a-tDCS (17.29 %), and a-tDCS alone (15.15 %), but not following strength training with sham-tDCS. These findings suggest that a single session of a-tDCS combined with unilateral strength training of the right limb increases maximal strength and cross-activation to the contralateral untrained limb.

Anodal tDCS Prolongs the Cross-education of Strength and Corticomotor Plasticity

To assess the efficacy of applying anodal transcranial direct current stimulation (a-tDCS) to the ipsilateral motor cortex (iM1) during unilateral strength training to enhance the neurophysiological and functional effects of cross-education.

The effects of anodal-tDCS on cross-limb transfer in older adults

OBJECTIVE: Age-related neurodegeneration may interfere with the ability to respond to cross-limb transfer, whereby bilateral performance improvements accompany unilateral practice. We investigated whether transcranial direct current stimulation (tDCS) would facilitate this phenomena in older adults. METHODS: 12 young and 12 older adults underwent unilateral visuomotor tracking (VT), with anodal or sham-tDCS over the ipsilateral motor cortex. Transcranial magnetic stimulation (TMS) assessed motor evoked potentials (MEPs) and short interval intracortical inhibition (SICI). Performance was quantified through a VT error. Variables were assessed bilaterally at baseline and post-intervention. RESULTS: The trained limb improved performance, facilitated MEPs and released SICI in both age groups. In the untrained limb, VT improved in young for both sham and anodal-tDCS conditions, but only following anodal-tDCS for the older adults. MEPs increased in all conditions, except the older adult's receiving sham. SICI was released in both tDCS conditions for young and old. CONCLUSION: Following a VT task, older adults still display use-dependent plasticity. Although no significant age-related differences between the outcome measures, older adults exhibited significant cross-limb transfer of performance following anodal-tDCS, which was otherwise absent following motor practice alone. SIGNIFICANCE: These findings provide clinical implications for conditions restricting the use of one limb, such as stroke.

Cathodal transcranial Direct Current Stimulation (tDCS) to the right cerebellar hemisphere affects motor adaptation during gait

The cerebellum appears to play a key role in the development of internal rules that allow fast, predictive adjustments to novel stimuli. This is crucial for adaptive motor processes, such as those involved in walking, where cerebellar dysfunction has been found to increase variability in gait parameters. Motor adaptation is a process that results in a progressive reduction in errors as movements are adjusted to meet demands, and within the cerebellum, this seems to be localised primarily within the right hemisphere. To examine the role of the right cerebellar hemisphere in adaptive gait, cathodal transcranial direct current stimulation (tDCS) was administered to the right cerebellar hemisphere of 14 healthy adults in a randomised, double-blind, crossover study. Adaptation to a series of distinct spatial and temporal templates was assessed across tDCS condition via a pressure-sensitive gait mat (ProtoKinetics Zeno walkway), on which participants walked with an induced 'limp' at a non-preferred pace. Variability was assessed across key spatial-temporal gait parameters. It was hypothesised that cathodal tDCS to the right cerebellar hemisphere would disrupt adaptation to the templates, reflected in a failure to reduce variability following stimulation. In partial support, adaptation was disrupted following tDCS on one of the four spatial-temporal templates used. However, there was no evidence for general effects on either the spatial or temporal domain. This suggests, under specific conditions, a coupling of spatial and temporal processing in the right cerebellar hemisphere and highlights the potential importance of task complexity in cerebellar function.

Studio degli effetti della stimolazione transcranica a corrente diretta (tdcs) sui potenziali evocati visivi steady state

I potenziali evocati visivi steady state (ssVEPs) consistono in una perturbazione dell’attività elettrica cerebrale spontanea e insorgono in presenza di stimoli visivi come luci monocromatiche modulate sinusoidalmente. Nel tracciato EEG si instaurano oscillazioni di piccola ampiezza ad una frequenza pari a quella dello stimolo. L’analisi nel dominio delle frequenze permette di mettere in evidenza queste oscillazioni che si presentano con un picco ben distinto in corrispondenza della frequenza dello stimolo. L’obiettivo di questo lavoro è quello di capire se la stimolazione transcranica in corrente continua (tDCS) ha degli effetti a breve e a medio termine sui SSVEPs. Si è studiato gli effetti della stimolazione anodica utilizzando un montaggio di stimolazione extra-cefalico (anodo posizionato su Oz e catodo sul braccio destro). L’esperimento prevede il flickering a 3 frequenze di interesse (12, 15, 20 Hz) di 3 quadrati colorati (rosso e giallo) su sfondo nero. Sono state quindi messe a confronto 4 condizioni operative: baseline, stimolazione sham, stimolazione anodica, condizione Post Anodica.L’esperimento è stato sottoposto a 6 soggetti di età tra i 21 e i 51 anni. Il segnale è stato acquisito da due canali bipolari localizzati nella regione occipitale (O1-PO7 e O2-PO8). È stato effettuato un filtraggio tra 3-60 Hz e a 50 Hz. Si sono stimate le PSD normalizzate rispetto alla condizione di riposo in baseline e le potenze nell’intorno della frequenze di interesse (12,15,20 Hz). I dati chiaramente artefattuali sono stati scartati mediante un’analisi esplorativa. Da qui è stato deciso di non includere nella statistica la stimolazione anodica. L’analisi statistica considera tre aspetti: effetto stimolazione, effetto frequenza ed effetto colore. In alcune configurazioni la stimolazione post anodica si è rivelata significativamente differente con ranghi medi delle colonne inferiori alle altre stimolazioni. Non ci sono differenze significative tra le frequenze. Il colore giallo è risultato significativamente maggiore al colore rosso.

Analisi delle potenzialita della tDCS applicata allo studio e alla riabilitazione dei processi cognitivi

L’estrema importanza degli aspetti neurologici che riguardano la vita dell’uomo, unitamente all’elevato grado di invalidità che le malattie del sistema nervoso sono in grado di provocare, ha portato nel corso del tempo gli studiosi a sviluppare metodologie di intervento sempre più accurate e specifiche nel tentativo di far fronte a queste complesse situazioni. Il sempre più frequente ricorso alle cure farmacologiche e alla psicoterapia ha saputo ben presto però sollevare numerose perplessità in merito all’efficacia di tali approcci. È a partire da questi presupposti che è stato possibile portare avanti nuovi studi sulla tDCS, un particolare tipo di apparecchiatura biomedicale basata sul concetto di elettrostimolazione cerebrale. Questo lavoro si propone di descrivere la capacità della tDCS di intervenire direttamente sui meccanismi che comunemente si verificano all’interno del cervello umano tramite il rilascio di corrente, nonché i numerosi miglioramenti che sono stati rilevati in seguito al suo utilizzo su soggetti umani. Si propone inoltre di mettere in evidenza le grandi potenzialità che essa è in grado di manifestare relativamente ai processi cognitivi, partendo dagli aspetti che riguardano il linguaggio, passando attraverso quelli propri della memoria e della conoscenza, fino ad arrivare a rivestire un ruolo di primo piano anche all’interno delle sfaccettature tipiche degli stati umorali.

tDCS: Stimolazione transcranica a corrente continua in ambiente sperimentale e clinico

Poiché i processi propri del sistema nervoso assumono una funzione fondamentale nello svolgimento della vita stessa, nel corso del tempo si è cercato di indagare e spiegare questi fenomeni. Non solo infatti il suo ruolo è di primaria importanza, ma le malattie che lo colpiscono sono altamente invalidanti. Nell’ultimo decennio, al fine di far luce su questi aspetti profondamente caratterizzanti la vita dell’uomo, hanno avuto luogo diversi studi aventi come strumento d’esame la stimolazione transcranica a corrente continua. In particolare questo lavoro si propone di analizzare gli ambiti di interesse dell’applicazione della tDCS, soffermandosi sulla capacità che ha questa metodica di indagare i meccanismi propri del cervello e di proporre terapie adeguate qualora questi meccanismi fossero malfunzionanti. L’utilizzo di questa stimolazione transcranica unitamente ai più moderni metodi di neuroimaging permette di costruire, o quanto meno cercare di delineare, un modello delle strutture di base dei processi cognitivi, quali ad esempio il linguaggio, la memoria e gli stati di vigilanza. A partire da questi primi promettenti studi, la tDCS è in grado di spostare le proprie ricerche nell’ambito clinico, proponendo interessanti e innovative terapie per le malattie che colpiscono il cervello. Nonostante patologie quali il morbo di Parkinson, l’Alzheimer, la dislessia ed l’afasia colpiscano una grande percentuale della popolazione non si è ancora oggi in grado di garantire ai pazienti dei trattamenti validi. E’ in questo frangente che la tDCS assume un ruolo di primaria importanza: essa si presenta infatti come una tecnica alternativa alle classiche cure farmacologie e allo stesso tempo non invasiva, sicura e competitiva sui costi.

Effects of transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production

Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left DPFC using electrophysiological and behavioural correlates during overt picture naming. Online effects were examined during A-tDCS by employing the semantic interference (SI-)Effect – a marker that denotes the functional integrity of the language system. The behavioural SI-Effect was found to be reduced, whereas the electrophysiological SI-Effect was enhanced over left compared to right temporal scalp-electrode sites. This modulation is suggested to reflect a superior tuning of neural responses within language-related generators. After -(offline) effects of A-tDCS were detected in the delta frequency band, a marker of neural inhibition. After A-tDCS there was a reduction in delta activity during picture naming and the resting state, interpreted to indicate neural disinhibition. Together, these findings demonstrate electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest that A-tDCS is capable of enhancing neural processes during and after application. The present functional and oscillatory neural markers could detect positive effects of prefrontal A-tDCS, which could be of use in the neuro-rehabilitation of frontal language functions.

Testing the involvement of the prefrontal cortex in lucid dreaming: A tDCS study

Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to induce lucid dreaming. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants' self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed.

Cathodal HD-tDCS on the right V5 improves motion perception in humans

Brain lesions in the visual associative cortex are known to impair visual perception, i.e., the capacity to correctly perceive different aspects of the visual world, such as motion, color, or shapes. Visual perception can be influenced by non-invasive brain stimulation such as transcranial direct current stimulation (tDCS). In a recently developed technique called high definition (HD) tDCS, small HD-electrodes are used instead of the sponge electrodes in the conventional approach. This is believed to achieve high focality and precision over the target area. In this paper we tested the effects of cathodal and anodal HD-tDCS over the right V5 on motion and shape perception in a single blind, within-subject, sham controlled, cross-over trial. The purpose of the study was to prove the high focality of the stimulation only over the target area. Twenty one healthy volunteers received 20 min of 2 mA cathodal, anodal and sham stimulation over the right V5 and their performance on a visual test was recorded. The results showed significant improvement in motion perception in the left hemifield after cathodal HD-tDCS, but not in shape perception. Sham and anodal HD-tDCS did not affect performance. The specific effect of influencing performance of visual tasks by modulating the excitability of the neurons in the visual cortex might be explained by the complexity of perceptual information needed for the tasks. This provokes a "noisy" activation state of the encoding neuronal patterns. We speculate that in this case cathodal HD-tDCS may focus the correct perception by decreasing global excitation and thus diminishing the "noise" below threshold.