Neuromodulation in Neuropsychological Rehabilitation: Applications, Benefits, and the Future of Non-Invasive Brain Stimulation

Clinical neuropsychologist Gabriel Perea Guzmán analyzes how non-invasive neuromodulation (tDCS, tACS, tRNS, TMS) enhances neuropsychological rehabilitation, its clinical applications and its future outlook in cognitive stimulation.

Introduction

For hundreds of years, humanity has altered brain activity through different methods and for various purposes, for example, the ritual use of mescaline and ayahuasca, the recreational use of opium, or the therapeutic use of cannabis. The history of using plants for ritual, medicinal, or recreational purposes is extensive. 

However, humanity has also attempted to modify brain activity using electricity. The Egyptians knew about the electric properties of the catfish, but it was not until Aristotle and Plato that the medicinal use of the torpedo fish was documented; it was used to treat migraines, gout attacks and other ailments. Yes, the first source of electricity for neuromodulation was a fish. 

Several centuries passed before Otto von Guericke built the electrostatic generator in 1660, considered the first electric stimulator of non-animal origin. From that moment on, the history of neuromodulation has been rapid, more so in some eras than in others. 

What is neuromodulation in neurorehabilitation? 

Part of the functioning of the central and peripheral nervous systems relies on two subsystems, one electrical and one chemical. Both are interdependent and, if you alter one, you alter the other. Epilepsy is the best example of how excitatory hypersynchronization alters glutamate and dopamine levels. 

Of course, other neuropsychiatric conditions involve a profound electrochemical disruption of different brain networks that translates into cognitive and behavioral impairments.

Definition of neuromodulation

The ability to modify brain activity for therapeutic purposes is called neuromodulation, and the term refers to the induction of changes in neuronal activity by administering electrical or magnetic agents to more or less specific areas to produce changes in cognition, emotional regulation, and behavior. 

Types of neuromodulation: invasive and non-invasive

Two types of neuromodulation are distinguished: invasive and non-invasive. 

Within invasive neuromodulation is Deep Brain Stimulation or DBS by its English acronym (Deep Brain Stimulation), a technique used for decades in conditions such as Parkinson’s disease or obsessive-compulsive disorder (OCD), which involves placing one or more stimulators through a surgical procedure; these stimulators deliver electrical pulses that modify brain activity. 

On the other hand, when we talk about non-invasive neuromodulation, we mainly refer to transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES).

Both use an electric field to regulate or modify the activity of circuits and brain networks, but they do so in different ways. 

Transcranial magnetic stimulation (TMS)

The TMS uses a coil through which a high-intensity current is passed creating a magnetic field; this coil is placed on the head so that the primary vector is perpendicular to the area to be stimulated. 

This magnetic field travels through the skin, bone and meninges and, once it reaches the neurons, it becomes a secondary electric field causing action potentials that propagate through circuits or networks. Depending on certain parameters such as frequency, greater or lesser excitability can be induced.

TMS received the first Food and Drug Administration (FDA) approval for the treatment of depression in 2008 and is the most used in the psychiatric field. 

However, it has also been used in clinical neurology for the rehabilitation of aphasias and motor disorders secondary to cerebrovascular events. 

Transcranial direct current stimulation (tDCS)

Meanwhile, transcranial electrical stimulation (tDCS) uses an electrode configuration that forms a circuit through which an electrical stimulus is delivered to the neurons of the cerebral cortex. Its main mechanism of action is the subthreshold modulation of resting membrane potentials. 

Unlike TMS, which produces changes in action potentials, transcranial electrical stimulation (tDCS) modulates spontaneous neuronal activity, that is, it changes the firing threshold and thus alters the probability of discharge. The underlying physiological mechanism for the induction of plasticity is mainly a glutamatergic process that involves NMDA receptors. 

Transcranial alternating current stimulation (tACS)

There are also different ways of delivering the electric field, which gives the technique greater versatility.

The most widely used, transcranial direct current stimulation (tDCS), delivers a low-intensity current continuously, modulating membrane potentials — excitatory or inhibitory — depending on the polarity of the electrodes.

Alternating current stimulation (tACS) uses an oscillating electric current, or sine wave, which influences how oscillations at different brain frequencies (beta, alpha, theta, and so on) synchronize.

Transcranial random noise stimulation (tRNS)

Finally, random noise stimulation (tRNS) uses a current whose amplitude and frequency vary randomly.

Of the three, tRNS is the least studied, while tDCS has the most evidence behind it. tACS, however, is beginning to gain ground in neuropsychological rehabilitation thanks to its capacity to modulate brain oscillations. All the areas that receive the stimulation — at least those lying between the two electrodes — are modulated in a similar way.

Integrating neuromodulation with rehabilitation tasks

In transcranial electrical stimulation (tES) it is essential to combine the technique with rehabilitation tasks or paradigms.

As we know, when facing a task one or more networks show changes in their activity, and those changes are encoded in spatial and temporal parameters. The techniques described make it possible to modulate the excitation or inhibition of one or more nodes of those networks at the same time as the person is meeting the cognitive demands of a task, thereby increasing or decreasing the probability of a given behaviour.

One example is implementing a tDCS protocol with anodal stimulation of the left prefrontal cortex at 1.5 mA which, over fifteen 20-minute sessions, concurrently uses Go/No-Go tasks to improve inhibitory control in people with predominantly hyperactive-impulsive Attention Deficit Disorder (ADD).

We should not forget that tDCS, tACS and tRNS only alter the probability of firing: the final result depends on the prior physiological state of the target network as well as on the type of concurrent stimulation.

Parameters in cognitive neuromodulation

The outcome of a neuromodulation programme will depend on the following parameters:

• Montage: the arrangement of the electrodes on the working surface, usually following the International 10/20 System for EEG. The polarity of the electrodes determines the probability of excitation (anode) or inhibition (cathode).
• Electrode: electrical conductors used to make contact with the non-electrical part of a circuit. They come in different sizes and shapes, which influences current density; ring electrodes achieve the most focal intensity. A saline solution or conductive gel is always used to improve conductivity.
• Ampere: the unit used to measure how much energy flows through a circuit per second. Milliamperes (mA) are one thousandth of an ampere, and the stimulation ranges normally used are 1, 1.5 or 2 mA. Broadly speaking, paediatric neuromodulation uses 1 or 1.5 mA, while 2 mA is chosen for adults.
• Type of current: there are three ways of delivering the electric current — direct current (tDCS), alternating or sinusoidal current (tACS) and random noise (tRNS).
• Concurrent stimulation: the presence or absence of a cognitive stimulation paradigm — for example, naming exercises while anodal stimulation of left anterior areas is applied. It can be online (occurring at the same time as the neuromodulation) or offline (before or after it).
• Session length: most sessions in clinical settings last 20 to 30 minutes.
• Number of sessions and frequency: in almost all clinical protocols, between 15 and 20 sessions are delivered, with a maximum of two sessions per day separated by a rest interval of two to three hours.

These variables are combined to build a protocol that responds to the patient’s needs and the therapeutic goals.

It is highly advisable to assess the patient before and after applying the protocol. We recommend that this assessment cover a physiological level, with EEG or event-related potentials; a behavioural level, with scales and self-reports; and the cognitive level, assessed through neuropsychological tests or batteries.

Conclusion

The combination of traditional neuropsychological rehabilitation and non-invasive neuromodulation begins to transform therapeutic approaches, opening a landscape full of possibilities. Increasingly more hospitals and specialized centers are incorporating these techniques into their programs, supported by growing scientific evidence and empirical results that show faster progress in patients’ recovery.

In pediatric and adolescent populations, the most used technique is transcranial electrical stimulation. Its non-invasive nature, portability and ease of application make it an accessible and safe alternative, especially when compared to transcranial magnetic stimulation, which requires greater motor control from the patient. Electrical stimulation has also evolved into more specific variants such as tACS, which promises positive effects on cognition given its potential to induce oscillatory synchronization between different networks that enhances certain cognitive processes.

However, to consolidate these advances it becomes essential to have rigorous evaluation systems that allow measuring the real impact of interventions. This implies assessing changes at multiple levels: behavioral, through instruments such as the BRIEF or the SENA; electrophysiological, through EEG recordings; and cognitive, with the application of neuropsychological tests and tasks. Only in this way will it be possible to clearly establish the scope of neuromodulation in clinical practice.

It is important to remember that these techniques, by themselves, do not constitute a therapy. Their true potential emerges when they are integrated into broad, coordinated rehabilitation programs, where the collaboration of multidisciplinary teams ensures a comprehensive approach. Thus, non-invasive neuromodulation stands out as a valuable resource, not isolated but in synergy with other strategies, marking the beginning of a new era in neuropsychological rehabilitation.

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“This article has been translated. Link to the original article in Spanish:”
Neuromodulación en la rehabilitación neuropsicológica: aplicaciones, beneficios y futuro de la estimulación cerebral no invasiva