factors affecting tDCS

Posted comment on ´Transcranial direct current stimulation: five important issues we aren`t discussing (but probably should be)` by J.C Horvath, O. Carter and J.D. Forte published online January 24th 2014 DOI 10.3389/fnsys.2014.00002 PMCID: PMC 3901383
In the research published here Horvath, Carter and Forte discussed five factors that may affect results from transcranial direct current stimulation (tDCS) studies. Normally, tDCS researchers and practitioners adjust and report three variables (current density, electrode position and stimulation duration), but from their meta analytical studies looking at the effects tDCS on the MEP amplitude in the motor cortex of healthy subjects, the authors suggested that researchers should also take into account the influences of inter-subject and intra-subject variability, sham stimulation and blinding, motor and cognitive interference and electric current influences.
In the case of inter-subject variability, Horvath, Carter and Forte`s meta-analytical research demonstrated between and within-group differences in published results. One example quoted showed that under identical experimental conditions one subject group had an MEP amplitude enhancement of 93.2, whereas another group had only 9.2 (Fricke et al, 2011). Horvath, Carter and Forte therefore concluded that researchers need to look at the stimulation response of individuals because of the observed differences between individuals. Intra-subject variability also was evident from Horvath, Carter and Forte`s meta-analytical study. On example demonstrating variability over time (Nitsche and Paulus, 2001) had one subject exhibiting an MEP amplitude enhancement of 295% whereas at another time only 5%. The authors suggested an explanation for such a difference in that it is difficult to target and maintain pulses in long experiments. Horvath, Carter and Forte also showed that individual responses could be masked when results are averaged for a group. Alonzo et al, 2012 looked at the same subjects over a period of days and found the baseline values varied, but the overall results did not. In their study Monte-Silva et al, 2010 found conflicting results when they performed the same experiment on consecutive days with healthy patients. On the second day there was a big decrease in MEP amplitude and a change in modulation. Horvath, Carter and Forte also report differences in results due to for example hormone and circadian rhythm differences and positioning of the coils. Therefore, they concluded that it is important to identify such factors that influence the effects of tDCS.
Horvath, Carter and Forte also described the importance, but difficulty in executing the necessary controls such as sham stimulation and blinding. Their meta-analysis showed unreliable results if carried out at all, eg. the researchers found for one particular experimental condition only 12% had controls. Even though for example in the case of blinding where there is a likelihood of identification of tDCS stimulation for either the practitioner (sees obvious vasodilation), or subject (experiences tingling, itching, burning), the authors stress the need for correct and appropriate controls in the tDCS studies.
Another factor that this paper`s authors found was a cause of variability in results is motor and cognitive interference. Behaviours occurring during or after the stimulation were found to impair or even abolish the effects of the stimulation. For example, Antal et al, 2007 reported that a cognitive task (a combined mathematics, language, geography, and history questionnaire) carried out during stimulation abolished the effects of both anodal and cathodal stimulation on MEP amplitude modulation. Quartarone et al, 2004 reported that even thinking about motor movement could abolish the tDCS effect, which Horvath, Carter and Forte described as being particularly problematic for the use of tDCS as a therapy.
The authors also found experimental conditions could also influence the amount of electric current experienced by the subjects. They found that variables such as hair thickness and sweat could affect electric current density and flow. Since hair is an insulator, dry hair has a high conductance and hence, hair thickness could play a role in the individual effects of tDCS. Researchers use saline to bridge the gap between the electrode and the scalp with thick hair, but this introduces the problem that it is difficult to ascertain accurately the electric current points of entry and exit. Other mechanical factors affecting the results were shown to exist. The electrode attachments methods influence electric current density and flow eg the amount of plastic used since plastic is non-conductive, or the rubber straps holding on the electrodes cause the periphery to flare upwards reducing the contact area.
With their paper, Horvath, Carter and Forte have discussed some of the factors that may affect the individual response to tDCS and hence, affect the results achieved for a group. They stress the need for further investigation so that the factors can be accurately identified.
This research is interesting because it details some of the problems with an electric current stimulatory method, transcranial direct current stimulation (tDCS) that has been promoted to the general public as for example, giving cognition and behavioural improvements, aids relief from depression (transmagnetic stimulation), and elicits temporary arousal of the minimally conscious. Probably the basis of the technique goes back to the research and hypotheses of Burr and Bender and their life fields, body electric current and voltage differences. Burr`s life fields hypothesized demonstrable voltage differences between physiological areas and the associated electric current was sensitive to geomagnetic fields producing a number of effects eg. hormone output, reaction times, number of lymphocytes, and cell division. In the brain, the Burr/Bender electric current flows back to front through the middle of brain originating from the reticular activating system. A negative potential is linked to the brain frontal regions and periphery of the nervous system and is associated with wakefulness, sensory stimulus, and muscle movements –the greater the activity, the greater the negative signal seen. The negative potential shifts to positive with sleep and anaesthesia returning to the negative as wakefulness returns. Ravitz showed that in the brain the voltage potentials were an indicator of normal mental functioning since he could establish a baseline voltage gradient between areas. Ravitz saw that the voltage gradient was different with illness or injury, but saw it return to normal after treatment. Mental functioning also appeared to be linked to the Burr and Bender electric current and voltage differences with the observation that the recall of grief during hypnotic regression led to an increased voltage, and they have been also associated with consciousness (modification of electromagnetic forces in the brain – McFadden and Pocket and quasi stable configurations representing thoughts – Lehman).
On a cellular level, the electric current reflects the neuronal membrane depolarization and signal transmission. Horvath, Carter and Forte explained that tDCS shifts the resting membrane potential and synaptic strength of neurons in a predictable and consistent manner. This manner is related to cell firing and not to blood circulation since research has shown no changes in blood flow with tDCS. From the anode-excite/cathode-inhibit model, neurons under the anode (positive electrode) undergo hypopolarisation leading to an increased likelihood of firing whereas neurons under the cathode hyperpolarise, hence leading to a decrease in firing. Therefore, it is possible that tDCS may lead to firing in areas close to the anode or under it or to an extent that would under normal levels of excitation at that time not be possible. This may be advantageous for overall brain area functioning since firing would be stronger (cells that fire together, wire together) and connections would be made to other parts of the brain. Synchronisation between firing cells would strengthen the overall effect and a change in brain functioning might be observed. In the case of the cathode and hyperpolarization, some areas naturally have cells whose response to signal transmission is hyperpolarisation, but in other cases the cells become more negative and hence, firing is decreased. In both cases, the observation that interference can occur with the tDCS effect is understandable. The direct firing effect for tDCS would be restricted to the areas around the anode and cathode and the path between. However, sensory input and conscious and unconscious processing of the information is still occurring, plus any thinking and reasoning. These, too, would fire neurons and groupings would form which would take priority over the tDCS temporary firing effect. Hence, any firing advantage would be lost, as is observed in the literature.
It is also clear that factors affecting in general cell firing and brain area functioning would also influence the tDCS results. Tiredness, drug levels, plus as Horvath, Carter and Forte suggested hormone levels, circadian rhythms and metabolic changes can all play a role in the results obtained. So can probably disease states such as depression, hyperactivity and anxiety. Just like with hair thickness, skull thickness, sweating the levels of these factors are individual and hence, experimental procedure and evaluation of the results needs to take them into account when formulating hypotheses about what tDCS does and how affective it is.
Since we´re chatting about the topic…….
….can we assume that performing tDCS on sleeping subjects or those under anaesthesia will give different results to subjects that are awake and that in the former the voltage differences may be related to the default network areas?
…..would linking tDCS with brain wave monitoring give an indication of how synchronization is affected by the process, particularly the theta and gamma oscillations. If the subjects were administered cannabinoids which disrupt neuronal grouping synchronization, would the application of tDCS overcome the effect?
….is it that if a subject was conditioned before the tDCS procedure to respond to a particular cue unconsciously, that during or after the tDCS the speed or type of that response would be affected by improving firing especially if the tDCS was applied to areas like the hippocampus, anterior cingulate cortex and prefrontal cortex?

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