As is well known, learning and memory involve explicit procedures (eg, declaratives) and implicit processes (eg, procedures), and improving one or both can contribute to improving learning [1]. Working memory refers to the temporary storage and manipulation of information needed for complex tasks such as language comprehension, attention, learning, and reasoning. One of the main goals of educational efforts is to develop techniques for improving learning and promoting better retention [1,2].

Today computer games are being developed not only for gamer entertainment but also in the field of health and education to improve one or more of the cognitive abilities of users. These games can improve problem-solving skills [3,4]. Brain events can be recorded in a noninvasive and flexible way through the electroencephalogram (EEG), and EEG-based applications were initially developed to help people with disabilities to communicate with machines; later they were used in video games as controllers and more recently as neurofeedback games [5]. Neurofeedback is a noninvasive, drug-free form of brain training reported to help with a variety of conditions, including pain, fatigue, depression, anxiety, sleep disturbances, and cognitive decline [6]. We can also include the implementation of a game to test the progress of trained individuals with a more flexible and interesting approach. It is a simple game application that uses visualization techniques to increase enthusiasm without being aware of being tested. As the system makes use of a participant’s direct attention to control a game, it works on a feed-forward mechanism [7]. Neurofeedback offers the possibility of endogenously manipulating brain activity as an independent variable, making it a powerful neuroscientific tool [8]. Some areas of clinical research involve comparing or combining neurofeedback with other interventions such as pharmacotherapy, behavioral therapy, and neurostimulation (eg, transcranial direct current stimulation [TDCS]).

TDCS noninvasively induces plasticity-related changes in neural circuits in vivo and is experiencing increasing use as a potential tool to modulate brain function [9]. There is growing evidence that TDCS-related outcomes are likely to be influenced by an individual’s brain state at the time of stimulation, that is, the effects show a degree of “state dependence” [10]. Fregni et al [11] demonstrated that anodic TDCS in the left dorsolateral prefrontal area leads to an increase in working memory performance, that is, increasing the accuracy of a task when compared to simulated stimulation of the same area. This study corroborates literature data showing TDCS as a tool that can significantly impact some aspects of knowledge [12].

TDCS is characterized by the administration of a single-phase electrical current of low intensity (0.5-2 mA) applied to the scalp through surface electrodes. This stimulation induces lasting changes in cortical neuronal excitability, both in animals and in humans [9]. TDCS-induced cortical modulation is dependent on the polarity of the applied current, and the effects are obtained by the movement of electrons. The poles of the electrodes used are the anode and cathode, with the anode being the positive pole and the cathode the negative pole. During the application of TDCS, the electrical current generated by the electrodes penetrates the skull, reaching the cortex [13]. Although most of the current dissipates between tissues superficial to the cortex, a sufficient amount of current reaches the cortical structures, thus modifying the membrane potential of the cells located there. It has been observed that anodic current increases cortical excitability, favoring neuronal membrane depolarization, while the cathodic current has an inhibitory effect by hyperpolarizing the neuronal membrane. TDCS has been shown to be a useful tool in the treatment of neuropsychiatric diseases and physical rehabilitation processes, being a safe and inexpensive form of noninvasive brain stimulation [10,11,14].

Some studies covering healthy individuals support the hypothesis that TDCS improves performance involving working memories, compared to simulated stimulation (placebo), and these effects can last up to 30 minutes after the end of the session. Nitsche et al [15] proposed general exclusion criteria for TDCS in healthy individuals: individuals must be free from unstable medical conditions or any disease that may increase the risk of stimulation, for example, neurological diseases such as epilepsy or acute eczema under the electrodes. Additionally, they must not have metallic implants near the electrodes. Side effects such as itchiness, a burning sensation, or a headache are common but usually mild and with no long-term impact. Thus, TDCS compares favorably with other therapeutic approaches such as antidepressants or transcranial magnetic stimulation [15].

Noninvasive neuromodulation has emerged as an alternative to replace other forms of treatment such as pharmacological treatments, which although effective, have a high rate of side or adverse effects. Among the different types, neurofeedback and TDCS have shown to be promising approaches that can modify brain wave oscillation and can be used in the development of skills for the self-regulation of brain activity [16]. However, no data were found in the literature associating these two features. The aim of this trial is to investigate the effectiveness of TDCS on the dorsolateral prefrontal cortex (DLPFC) associated with neurofeedback evaluating behavioral and physiological parameters of healthy college students. We hypothesize that there will be a significant increase in declarative memory responses and increased cerebral blood flow using the proposed protocol.

The trial and enrollment began in July 2022. The statistical analysis for the secondary outcomes are currently being performed.

We believe that the resources used in this study can help improve some aspects of declarative memory, since learning and memory processes modify the brain. Strategies to enhance the acquisition, storage, and use of information must be able to sensitize (motivate) and involve volunteers in the learning process, thus clarifying their role.

The performance of a task depends on ongoing brain activity that can be influenced by attention, excitement, or motivation. Scientific studies confirm that mindfulness leads to better performance, health, and well-being. However, these factors that modulate cognitive efficiency are nonspecific, can be difficult to control, and are not suitable to specifically facilitate neural processing.

The first stages of memory consolidation involve the stabilization of structural and functional neural changes and other neural changes generated by learning. New methods of memory consolidation optimization are being suggested (authors) in the role of neuromodulation.

The human brain is a highly interconnected network with high information processing efficiency. This efficient processing network operates through specialized structures and functions [21]. Among the essential functions of humans, memory requires significant attention from researchers because it is the ability to store and evoke learned knowledge [2]. The storage and use of learned information in the brain are fundamental for the interaction and modulation of human behavior and the adaptation and interaction of individuals with their environment [22].

In recent years, there has been an increase in technological improvement and neuroscientific discoveries aimed at new forms of training focusing on increasing memory performance [23].

As already described, neurofeedback is a brainwave training technique used to improve performance in terms of creativity, attention, and memory [24]. It has also been used as a potential cognitive and behavioral adjuvant for healthy individuals [6,25]. However, the effectiveness of neurofeedback with healthy participants received criticism from the scientific community since most studies failed to provide evidence for changes in behavioral and electrophysiological measures, mainly due to methodological deficiencies such as the lack of a sham/control group [26]. In response to this lack of reliability, Wang and Hsieh [3] researched young and older adult individuals to investigate the effectiveness of the cortical activity training protocol on attention and working memory performance. The authors observed better performance in older adults, with a significant improvement in memory among the young [3].

Although recent discoveries are addressing and answering old and new questions, the current findings provide insights into the underlying mechanisms of neurofeedback training in cognitive function. Furthermore, the results indicate that an intervention program protocol could be effective against cognitive aging and memory decline [3].

The future of neurofeedback research lies primarily in mobile recording and real-time feedback of the emotional and cognitive states of the individuals being evaluated. Due to volume conduction (the ability to measure electrical potentials at a distance from their source generators), single channels, regardless of where they are placed on the scalp, can capture a substantial fraction of all brain dynamics. Indeed, Rebolledo-Mendez et al [25] used attention levels as an input to interface systems between the brain and a computer, and found that the device provides accurate readings regarding attention since there is a positive correlation between measured and self-reported attention levels. However, setbacks observed by the authors included difficulties using the device due to the size of the head, interference with the hair, and no indicator for low batteries [25].

The primary reason for selecting this equipment is that it is a single dry electrode system, a type of EEG that does not require any substance or solution between the skin and the electrode. This feature makes the testing process more agile and reduces the individual’s discomfort. Johnstone et al [27] reported that the results obtained with this type of EEG are comparable to other devices that use different sensors and conductive substances. Additionally, it is easy to use and access the data since the equipment communicates with a computer via Bluetooth, making analyses and treatment more efficient. Furthermore, this technology comes at a low cost. These characteristics facilitate research and allow acquisition by any individual without substantial training [27].

The other device suggested for applying this protocol uses TDCS. This technique has been shown to elicit lasting effects in different protocols and diseases. TDCS provided the beneficial effect of anodic direct current stimulation of increased excitability in simple reaction times and implicit motor learning when stimulating the primary motor cortex [28] and improved learning of a visual-motor coordination task by stimulating the primary motor area or the V5 visual area [29].

Regarding its action on working memory, Fregni et al [11] demonstrated that anodic stimulation in the left DLPFC improves working memory performance. This effect depends on the polarity of the stimulation and is specific to the stimulation site. The results of Fregni et al [11] were further corroborated by Javadi and Walsh [30], who performed two experiments involving 32 participants who performed a series of word memorization tasks. This task was performed during simulated anodic and cathodic stimulation to the left DLPFC. Participants in the first experiment performed the same task with anodic TDCS of the primary motor cortex (M1). The results indicated that active stimulation of the left DLPFC leads to an improvement or attenuation of verbal memorization depending on the polarity of the stimulation. For example, during encoding, anodic stimulation of the left DLPFC improved memory, while cathodic stimulation of the same area impaired memory performance in later recognition. Anodic stimulation of M1 did not affect later recognition [30]. Smirni et al [31] observed and confirmed the same results.

To date, we have not found scientific studies using the association of the two techniques. We believe that using neurofeedback in conjunction with TDCS can potentiate the effects of training and thus provide greater effectiveness and long-term effects on the memory of individuals. In the long term, we expect that our results might further comprehensive programs for these conditions.