Online TDCS -Can Brain Stimulation Make Cognitive Training More Effective?
What if we could give the brain a little nudge when it is learning? This is the basic premise behind "online" transcranial direct current stimulation (tDCS). Here, "online" does not mean using the internet to deliver treatment. In neuromodulation research, "online" generally means applying stimulation during the cognitive, behavioral, or therapeutic activity you want to influence.
Rather than having patients receive tDCS for 20-30 minutes while sitting passively, online approaches would involve administering stimulation while patients are performing working memory exercises, attention training, cognitive control tasks or selected components of cognitive behavioral therapy (CBT).
The rationale is quite simple: if tDCS can facilitate plastic change in the brain at a time when the brain is ready for change, why shouldn't we deliver stimulation at the time we want the brain to learn that experience? There are many applications of this idea, including depression, cognitive impairment, stroke rehabilitation, and potentially many other neuropsychiatric disorders.
The evidence for combining tDCS with cognitive interventions has been encouraging in some domains but results have remained heterogenous and individual responses can vary substantially.
How does tDCS work?
Transcranial direct current stimulation is a non-invasive type of neurostimulation whereby a small electric current is applied through electrodes on the scalp. Unlike electroconvulsive therapy (ECT), tDCS will not cause a seizure. The current used is very low and the goal is not simply to turn the brain "on" or "off". Rather, tDCS can alter the excitability of neurons underneath and between the electrodes.
One way to conceptualize this idea is to picture that neural networks are always balancing excitatory and inhibitory inputs. Whether a neuron fires depends partly on how close its membrane potential is to the threshold required for firing. TDCS may change this electrical environment and therefore change how responsive a population of neurons is to new activity. However, an important misconception needs to be avoided: tDCS will not simply make the stimulated part of the brain work harder. Effects of tDCS are strongly dependent upon parameters of stimulation, anatomical characteristics of the individual, state of the brain during stimulation and what the person is doing during stimulation. State dependence is especially important to online tDCS. The same stimulation may produce different behavioural effects in two people or even the same person under different conditions. The brain is not an inert piece of tissue waiting for electrical activation. It is a dynamic system whose response to stimulation depends partially on what it already was doing.
Neuroplasticity requires experience
Adult brains have substantial capacities for plasticity. Repeatedly practicing a task; changing a behaviour; learning a new skill; or participating in rehabilitation can create experience-dependent changes in neural networks. The general ability of the nervous system to modify its structure and function in response to experience is called neuroplasticity.
Cognitive training uses neuroplasticity
Training programs for cognition attempt to use neuroplasticity by requiring repeated, highly structured practice. For example, a patient with cognitive deficits due to Mild cognitive Impairment (MCI) may repetitively practice on cognitive functions such as working memory, attention, processing speed, etc. Likewise, CBT encourages the brain to repetitively practice new ways of interpreting situations and new ways of responding to situations. A person with depression learns to recognize automatic negative thoughts; analyse cognitive distortions; and generate alternative interpretations. A person with anxiety learns to tolerate feared situations without relying on safety behaviours or avoiding the feared situation.
In these examples, the brain is being encouraged to learn. Therefore, there exists a fascinating opportunity for neuromodulation: perhaps stimulation should occur while the brain is engaged in learning, rather than at separate times. That is, instead of viewing tDCS and cognitive/behavioural therapy as two separate interventions, they could potentially be temporally linked so that stimulation occurs during the activity we are trying to enhance the neural effects of. This is often referred to as activity dependent or state dependent modulation of brain function. The idea here is that tDCS may alter the likelihood that plasticity will occur while the cognitive/behavioural task provides the experience to guide that plasticity.
Why use tDCS with cognitive training?
Consider a patient who has had a stroke and requires post-stroke rehabilitation. An occupational therapist devotes 30 minutes of repetition to a specific cognitive/motor function. During this time, the patient engages cognitively and motorically with the neural networks responsible for that function. If stimulation can affect the responsiveness of these neural networks during practice, then theoretically these two treatments may support each other through what is sometimes referred to as a "priming" effect. Intensive and repetitive practice of a task has been recognized by rehabilitation professionals as a fundamental component of effective rehabilitation. The addition of neuromodulation represents another layer of potential effectiveness by attempting to modify the neural conditions under which practice takes place. Thus, the goal is not just to stimulate the brain, but to stimulate it while it is doing something meaningful.
Evidence supporting this combination of treatments began emerging about a decade ago. A systematic review & meta-analysis of 15 studies involving 629 participants evaluated the combined application of tDCS with cognitive training across neurodegenerative disorders and psychiatric disorders. Investigators determined that there was a small statistically significant advantage for combined treatment relative to either intervention alone on measures related to attention & working memory. Effects on other cognitive areas were weaker & differences among studies were numerous.
Subsequently a larger trans-diagnostic systematic review assessed 72 studies involving more than 2500 participants. Sensitivity analyses indicated that the largest consistent benefit from combining non-invasive brain stimulation with cognitive training was observed in learning & memory domains; however, the magnitude of the effect size was relatively small and there was very little evidence that benefits persisted over extended periods. While these results provide encouragement toward pursuing this line of investigation further, they also illustrate why researchers are now asking the more important questions about how stimulation interacts with training processes. Timing of stimulation; neural target; type/cognitive task; intensity & duration of training; and individual characteristics of patients are examples of variables influencing efficacy.
Thus, while it appears that tDCS can be beneficial in conjunction with cognitive training (especially with respect to learning/memory), the critical question facing the field today is no longer whether tDCS and cognitive training should be combined but how these elements should interact to optimize benefits for each individual.
From cognitive training to CBT
The concept gains special interest in psychiatry due to the fact that Cognitive training (ct) and CBT are alike in many ways, albeit they have different focuses. They both involve "active learning". Ct typically refers to training of specific Cognitive skills e.g. Attention, working memory, processing speed or Cognitive control. On the other hand, CBT is aimed at modifying maladaptive patterns of thought and behaviour. However, both require the individual to repeatedly use the same type of cognition and create new answers.
Let us consider depression. Depression can manifest through a variety of Cognitive impairments; i.e., attention deficits, decreased working memory capacity, reduced Cognitive flexibility, or difficulty in disengaging from negative stimuli. A typical CBT session involves identifying automatic thoughts, evaluating alternative perspectives and developing behavioural methods to counteract them. All of these tasks rely upon recruitment of Cognitive-control networks, including prefrontal areas. Given that the dorsolateral prefrontal cortex (DLPFC) has been identified as a major focus area in many tDCS depression studies, it follows logically that a paradigm involving application of tDCS together with active engagement in either Cognitive or therapeutic activities represents a promising paradigm.
The logical sequence is as follows: identify the dysfunctional Cognitive process; employ that Cognitive process in the therapeutic setting; apply the neuromodulatory technique during the engagement of that process; perform the above-mentioned steps enough times so that learning occurs and is consolidated. The aforementioned is merely speculative and hypothesized; it is not yet an empirically supported therapeutic mechanism that has proven effective in regular clinical settings. Studies investigating combinations of tDCS and CBT-like therapies are already underway. An example includes a study published in 2015 comparing group CBT with active tDCS versus group CBT with sham tDCS in adolescents with depression. While both groups exhibited significant improvements in depressive symptom scores, the group that received active tDCS had significantly larger decreases in their scores and had a higher proportion of responders. Despite the encouraging findings in this study, a more recent systematic review and meta-analysis of all available sham-controlled trials using tDCS as an adjunctive therapy to Cognitive-behavioural interventions for unipolar depressions found no statistically reliable additive benefits of active tDCS when added to standard CBI. The authors noted a wide range of methodological variability among the included studies and insufficient statistical power to detect small-to-medium-sized effects.
As mentioned previously, there is much to inform both the clinician and the patient regarding tDCS. Patients and clinicians should view online tDCS as an experimental therapeutic modality (as opposed to a substitute for existing forms of psychotherapy or pharmacotherapy).
What might an online tDCS session look like?
An online tDCS session may appear almost indistinguishable from a traditional session from the patient’s perspective. After proper evaluation of the patient and placement of electrodes, the patient engages in some form of structured Cognitive or therapeutic exercise(s) while receiving concurrent tDCS for a designated time frame. The tDCS is preferably applied via a gradual increase at the start of the session and decrease at its conclusion; the majority of the session will consist of the patient performing the Cognitive/therapeutic task(s) while simultaneously receiving tDCS.
Example: a session could commence with approximately 2 – 5 minutes to prepare electrodes and allow for stimulation to ramp-up. Subsequently, the next 20 – 25 minutes will be comprised of Cognitive training/exercise and/or structured therapeutic activity, which will take place while the patient receives stimulation. Finally, the stimulation will be turned off while the patient completes a brief self-assessment concerning their subjective symptoms/adverse effects/task performance.
Ultimately, the stimulation parameters (amplitude/intensity), electrode configuration/montage, duration of stimulation and nature/characteristics of Cognitive intervention will be determined exclusively based on the underlying clinical diagnosis and respective therapeutic protocol utilized. As stated earlier, however, the important aspect here is that the patient is not simply receiving electrical impulses while remaining passive. Rather, the Cognitive/behavioural component(s) represent integral components of the treatment intervention. Consequently, online tDCS shares similarities with rehabilitation paradigms rather than passive medical procedures. Stimulation presents a physiological environment conducive to learning and the behavioural intervention represents the information that needs to be learned.
Where could this approach be useful?
Depression
Depression has been one of the most studied psychiatric uses of tDCS. Combining this with Cognitive-control training is especially promising given that Cognitive control deficits are common in depression and the persistence of negative cognition is characteristic of many depressive episodes. A prior study examining the effectiveness of tDCS when combined with Cognitive control training showed that it was possible to combine these two approaches (as long as they were conducted in conjunction with each other). Although this earlier study did show that there would likely be some degree of additional improvement in depression symptoms due to the use of both treatments; however, this improvement was relatively small.
There have since been numerous studies exploring the possibility of enhancing the benefits from psychological treatment through the addition of tDCS. However, as with much research into this area, results have been inconsistent, thus suggesting that in order to take full advantage of tDCS, clinicians will need to determine which specific Cognitive processes, therapeutic activities and/or patient groups may require enhanced neuromodulatory input.
Cognitive impairment and neurodegenerative disorders
Cognitive training is now being applied to support the maintenance and enhancement of abilities related to attention, working memory and executive function in patients suffering from a variety of neurological and psychiatric illnesses. In essence, the goal of using tDCS is to augment the brain's ability to respond to the training provided. While some studies suggest that tDCS can augment the enhancement produced by Cognitive training in areas related to working memory and learning, the amount of augmentation has generally been small. Furthermore, there appears to be growing consensus within the field that merely applying tDCS at a random time point relative to a training regimen will probably not produce clinically meaningful levels of benefit. Therefore, clinicians will need to carefully match their selection of Cognitive tasks with their stimulation targets and stimulation times in order to maximize the potential for positive clinical outcome. Ultimately, this could result in protocols where the specific type(s) of Cognitive tasks performed by a patient become part of the clinician's prescription for tDCS.
Stroke rehabilitation
Stroke recovery represents the most clear-cut example of how the approach outlined above can be applied. It is well established that recovery from stroke requires repeated performance and experience-dependent plasticity. As previously discussed, computerized Cognitive training has shown promise in improving several Cognitive domains post-stroke, whereas tDCS has been extensively explored as a means to enhance rehabilitation efforts.
The next frontier: personalised online tDCS
Next frontier for online tDCS
As we move forward with research into tDCS there will be another hurdle to overcome: the fact that one stimulation method does not result in the same brain responses in everyone.
What is applied through electrodes at the scalp does not equate to the electrical field that reaches a specific area of the cortex. Skull thickness, amount of cerebrospinal fluid, cortical structure and placement of electrodes can all impact the final electrical field. Studies using computational modeling have demonstrated significant differences in the electrical fields created by the same amount of tDCS in different individuals. These differences may contribute to the mixed results found in some tDCS research. In addition, this is part of why so many people in the field are now looking toward personalized stimulation.
In the future, tDCS protocols may need to take into account an individual’s brain anatomy; stimulation location; their cognitive profile and possibly their immediate brain activity. Rather than simply prescribing a standard dosage (e.g., "2ma for 20min"), we may soon begin asking a more advanced version of the following questions: what is the best stimulation for each individual, where should the stimulation occur, when is it best to deliver the stimulation, what task should the individual perform while receiving the stimulation, and what is the most appropriate time for the stimulation to be received? A much more advanced approach to precision neurostimulation.
The promise and the caveat
tDCS exists at a very exciting point of convergence among psychotherapy, cognitive remediation and brain stimulation. While its potential benefit does include increasing excitability in the brain, a more appealing concept is that neuromodulation can be paired with learning. During stimulation, the brain may become ready for plastic change. The therapeutic or cognitive task provides the learning experiences that direct that plasticity.
However, the science behind tDCS has yet to be fully developed. The literature regarding tDCS used in conjunction with cognitive training/therapy indicates promising results regarding learning-related functions including memory, attention and working memory. However, these results vary greatly across study in terms of stimulation parameters; cognitive tasks; subject population(s); and outcome measures. Another major concern is that there may be great variation from person-to-person.
Thus, there is a risk in implying that tDCS can serve as a substitute for rehabilitation and/or psychotherapy ("rewiring" the brain). As with other treatments, the effectiveness of tDCS will depend upon factors like repetition of treatment sessions; Motivation of the client; etc. TDCS may potentially aid in improving an individual's ability to capitalize on a learning experience if provided appropriately.
This may represent the most interesting future direction for neuromodulation: utilizing neurostimulation to enhance the effectiveness of rehabilitation/psychotherapy rather than substituting it.