Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation (NIBS) technique that induces transmembrane neuronal potential and thus influences the level of cortical excitability (see review Nitsche et al., 2008; Zaghi et al., 2010). It is thought that the neuronal changes associated with the persisting effects of tDCS are analogous to activity-dependent synaptic plasticity, i.e., long-term potentiation (LTP) and long-term depression (LTD; Di Lazzaro et al., 2012). There are a number of lines of evidence for the induction of LTP by DC stimulation. Fritsch et al. (2010) showed that the synaptic effects of direct current stimulation which induced LTP in mouse motor cortex (M1) slices is dependent on N-methyl-D-aspartate (NMDA) receptor activation. Ranieri et al. (2012)further demonstrated that DC stimulation applied to rat brain slices modulated LTP in a polarity specific manner, i.e., modulation of LTP was increased by anodal and reduced by cathodal DC stimulation. Pharmacological studies have also shown that tDCS after-effects are affected by NMDA receptor antagonist dextromethorphane (Nitsche et al., 2003a; Ranieri et al., 2012). These results strongly indicate that the effects induced by tDCS share similarities with activity-dependent synaptic plasticity, such as LTP and LTD (Di Lazzaro et al., 2012). Furthermore, DC stimulation also modulates LTP induced by other NIBS techniques and interferes with learning and memory processes which are strongly associated with LTP (Kim and Linden, 2007). Thus tDCS is considered to have capacity to induce LTP/LTD-like plasticity.
The application of tDCS over M1 elicits changes in corticospinal excitability in a polarity specific manner: motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS) are potentiated by anodal tDCS and suppressed by cathodal tDCS (Nitsche and Paulus, 2000). Furthermore, the technique is extremely well tolerated by most individuals and allows an easily applied sham condition to which the participant is readily blinded. Finally, it has been shown that tDCS can be combined with motor and cognitive tasks to facilitate learning.
Despite the abundance of research on the behavioral effects of tDCS on motor function (see reviewReis and Fritsch, 2011) showing increased levels of performance in both healthy (Nitsche et al., 2003b; Antal et al., 2004; Vines et al., 2006) and clinical populations, such as stroke patients (Hummel et al., 2005; Kim et al., 2009), only a limited number of studies have investigated the effects of tDCS over M1 in healthy older adults (Hummel et al., 2010; Zimerman et al., 2013). These two studies did not, however, assess the tDCS-induced changes in corticospinal excitability. While the behavioral improvements suggest that the plastic changes within M1 induced by tDCS were substantial enough to elicit behavioral change, it is unknown whether these neural changes varied relative to the changes expected in young adults. Indeed, there is some evidence that older individuals may have reduced neuroplasticity (Fathi et al., 2010), at least when assessed by the paired-associative stimulation (PAS) technique. The overall conclusion that can be drawn is that there is no consensus on the degree to which neuroplasticity is affected by healthy aging (Oliviero, 2010).
Recently, brain-derived neurotrophic factor (BDNF) a neurotrophin within the secretory protein family, has been suggested to play a crucial role in neuroplasticity and associated learning (Pascual-Leone et al., 2011). The most common forms of BDNF polymorphism are Val66Met and Val66Val (Lu, 2003). These BDNF polymorphisms have been shown to differentially modulate human cortical plasticity as a response to training (Kleim et al., 2006), brain stimulation (Cheeran et al., 2008), and motor learning (Fritsch et al., 2010). Thus, the BDNF example suggests that individuals with a certain genetic predisposition may show a different response to interventions that modulate brain plasticity – either in a use-dependent manner (i.e., motor or cognitive training) or induced via NIBS techniques. The relationship between tDCS induced aftereffects and BDNF genotype, however, is still unclear.