The procedures are considered completely safe and have also been used to treat depression, anxiety, and chronic pain (image: DC Studio/Freepik)
Published on 01/19/2026
By José Tadeu Arantes | Agência FAPESP – A clinical study involving several centers will test an innovative method for treating unilateral spatial neglect (USN), a disabling sequela of stroke that affects perception of one side of space and hinders functional rehabilitation. The project, called the Titan Trial, investigates combining two noninvasive neuromodulation techniques – transcranial direct current stimulation (tDCS) and theta burst (TB) transcranial magnetic stimulation – with task-based physiotherapy sessions.
USN causes the person to forget or not perceive one side of the body or environment. For example, they may only eat food from the right side of their plate, collide with objects or people on their left, or comb, shave, or apply makeup only to the right side of their head. They may also not hear someone call their name from the left. USN is not a motor or visual deficit, but rather a perceptual deficit that can persist even if the affected individual regains strength and movement.
“This new initiative is an offshoot of our line of research in post-stroke neurorehabilitation, supported by a Regular Grant from FAPESP,” says Rodrigo Bazan, a neurologist, professor at the Botucatu School of Medicine of São Paulo State University (FMB-UNESP), and coordinator of the study.
The initiative builds on research that yielded promising results in a previous study by the same group. With support from FAPESP, the researchers tested the effectiveness of anodal (stimulatory) tDCS in patients with lesions in the right cerebral hemisphere, particularly in the parietal region. This region is responsible for perceiving space on the left side of the body.
“In that study, which we called the Eletron Trial, we showed that anodal electrical stimulation applied to the right parietal region promotes brain plasticity and reduces spatial neglect,” Bazan recalls. “Six articles were published, including one in Annals of Neurology, one of the most respected journals in neuroscience.”
Based on these results, the group decided to move forward with a more comprehensive and potentially more effective approach. In the Titan Trial, patients receive electrical stimulation of the damaged (right) hemisphere and continuous theta burst (inhibitory) transcranial magnetic stimulation of the contralateral (left) hemisphere. “The logic is this: stimulate the side that suffered the injury and inhibit the other side, which, due to poor compensation, may be hindering recovery,” Bazan explains.
When a stroke occurs, the injured hemisphere may become hypoactive, while the contralateral hemisphere may become hyperactive, causing an interhemispheric imbalance. The combination of the two techniques helps rebalance brain activity and enhance the effects of physiotherapy.
These procedures are considered completely safe. They have been used in other treatments for depression, anxiety, chronic pain, and motor changes resulting from stroke. Electrical and magnetic stimulation are not painful, causing at most a slight tingling or pressure in the head, which passes quickly.
“We’re using the best of both techniques: anodal [stimulatory] tDCS, which has already shown good results in our previous study, and [inhibitory] TB, which allows for faster and more concentrated sessions, with great potential for impact on cortical reorganization,” says Luana Aparecida Miranda Bonome, a physiotherapist and doctoral student in the graduate program in Physiopathology in Clinical Medicine at FMB-UNESP. The study is part of her research project.
According to Bonome, what sets the Titan Trial apart is the combination of stimulatory and inhibitory techniques with specific physiotherapy. “All patients undergo physiotherapy focused on specific tasks, which enhances the effects of neuromodulation. There’s no point in opening the window of brain plasticity and not taking advantage of it with a functional intervention,” Bonome comments.
The multicenter study includes participation from UNESP in Botucatu and institutions in various regions of Brazil. These include the Federal University of Triângulo Mineiro (UFTM), where Gustavo Luvizutto, a physiotherapist and active team member, played an important role in the previous study (Eletron Trial); the University of São Paulo (USP); the State University of Campinas (UNICAMP); and specialized centers in Salvador, Campo Grande, and Joinville, among others. There is also international collaboration with the University of Toronto in Canada, which will participate in the analysis of clinical outcomes. Physiotherapists Brenton Hordacre and Emily Ramage are researchers from Australia with experience conducting clinical trials and neuromodulation research. At least 51 patients will be recruited and divided into three groups: combined active stimulation, isolated electrical stimulation, and a placebo group. All groups will receive task-oriented physiotherapy.
“The selection of participants is thorough. We only include patients with right-hemisphere ischemic stroke and a confirmed diagnosis of spatial neglect. We exclude cases involving bilateral lesions, severe cognitive deficits, or comorbidities that would compromise treatment adherence,” says Bonome.
The interventions will be carried out over 15 sessions, with intermediate and follow-up assessments after three, six, and 12 months. These interventions and evaluations will take place at the Clinical Research Unit (UPECLIN) of FMB-UNESP, a major supporter of the project. The main outcome monitored is the reduction of USN, in addition to analyzing improvements in functionality, autonomy, quality of life, and self-efficacy. The researchers hope that the results will establish the clinical application of combined neuromodulation as an effective and feasible strategy within the SUS (Brazil’s national public health network). “This will be an important step toward transforming advanced technology into everyday healthcare practice,” Bazan concludes.
Source: https://agencia.fapesp.br/56979
