Neural Mechanisms of Neuro-Rehabilitation Using Transcranial Direct Current Stimulation (tDCS) over the Front-Polar Area

Abstract

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation (NIBS) technique that applies a weak current to the scalp to modulate neuronal excitability by stimulating the cerebral cortex. The technique can produce either somatic depolarization (anodal stimulation) or somatic hyperpolarization (cathodal stimulation), based on the polarity of the current used by noninvasively stimulating the cerebral cortex with a weak current from the scalp, making it a NIBS technique that can modulate neuronal excitability. Thus, tDCS has emerged as a hopeful clinical neuro-rehabilitation treatment strategy. This method has a broad range of potential uses in rehabilitation medicine for neurodegenerative diseases, including Parkinson's disease (PD). The present paper reviews the efficacy of tDCS over the front-polar area (FPA) in healthy subjects, as well as patients with PD, where tDCS is mainly applied to the primary motor cortex (M1 area). Multiple evidence lines indicate that the FPA plays a part in motor learning. Furthermore, recent studies have reported that tDCS applied over the FPA can improve motor functions in both healthy adults and PD patients. We argue that the application of tDCS to the FPA promotes motor skill learning through its effects on the M1 area and midbrain dopamine neurons. Additionally, we will review other unique outcomes of tDCS over the FPA, such as effects on persistence and motivation, and discuss their underlying neural mechanisms. These findings support the claim that the FPA could emerge as a new key brain region for tDCS in neuro-rehabilitation.

Keywords: Parkinson’s disease; neural mechanisms; the frontal pole area; transcranial direct current stimulation.

Figure 1

Relations between the PFC hemodynamic activity in the hand movement tasks and task performance. Reproduced from Kobayashi et al. (2021) [16] under a CC-BY license. Topographical maps of the PFC cortical activity shown as effect sizes in the three consecutive trials in the sequential motor (SM) (A1) and control motor (A2) tasks. NIRS recording channels on the head are shown as yellow dots. (B) Positive relationships between changes in PFC cortical activity and SM-task error reduction, which occurred on the first and second trials. The dotted line indicates a regression line.

Figure 2

Averaged hemodynamic responses during a performance of a peg board task. Reproduced from Ishikuro et al. (2014) [17] under a CC-BY license. Cortical activity (changes in Oxy-Hb) rapidly increased during the task at the FPA and seven somatosensory and motor-related areas (supplementary motor area (SMA), left premotor area (Lt-PMA), right premotor area (Rt-PMA), left primary motor area (Lt-M1), right primary motor area (Rt-M1), left primary somatosensory area (Lt-S1), and right primary somatosensory area (Rt-S1)). Changes in Oxy-Hb, total-Hb, and deoxy-Hb concentrations are shown by red, green, and blue lines, respectively. Arrows represent the onset of the task.

Figure 3

FPA role in motor learning in a peg board task. Reproduced from Ishikuro et al. (2014) [17] under a CC-BY license. (A) Positive relations between task performance gain and FPA Oxy-Hb gain. The dotted line indicates a regression line. Each filled symbol indicates data for each subject. (B) Effects of tDCS over the FPA on task performance (peg scores) in the peg board task. *, p < 0.05.

Figure 4

FPA role in improving performance in neurofeedback (NFB) training for six days. Reproduced from Ota et al. (2020) [20] under a CC-BY license. (A) Averaged task-related responses, shown as NIRS-SPM T-statistic maps, during a performance of a peg board task after the real (A1) and sham (A2) neurofeedback (NFB) training. The real NFB training induced cortical activation in the somatosensory and motor-related areas (A1), while the sham NFB training induced SMA activation (A2). (B) Relationships between Oxy-Hb gain in the hand area of the left primary motor cortex (lateral Lt-M1) and performance gain in the peg board task (B1), and those between cortical activity in the FPA during the performance of the real NFB training on the 6th day of the training, and cortical activity in the somatosensory and motor-related areas during performance of the peg board task after the real NFB training (B2). The dotted lines indicate regression lines. The data in each circle indicate data from each subject.

Figure 5

Effects of tDCS over the FPA on PD symptoms (A) (reproduced from Ishikuro et al., 2018 [15] under a CC-BY license) and neuromelanin (NM) imaging in the midbrain (B) (created from the original NM-MRI data by Ishikuro et al., 2021 [19]). (A) Effects of the tDCS on motor disturbance (A1) and nonmotor functions (attention/executive functions) (A2). Motor disability was evaluated with the Unified PD Rating Scale (UPDRS (part III: motor examination)) after intervention of each tDCS stimulation (anodal, cathodal, and sham tDCS). Nonmotor functions were assessed with the Trail Making Test A (TMT-A). ∗, p < 0.05. (B) Imaging of dopamine neurons by neuromelanin magnetic resonance imaging (NM-MRI) in the substantia nigra compacta (SNc) before (B1) and after (B2) FPA tDCS in one PD patient. Red pixels indicate NM-sensitive areas in the SNc, where dopamine neurons are located.

Figure 6

Hypothetical neural mechanisms of tDCS over the FPA in neuro-rehabilitation. Dopamine neurons in the SNc and VTA receive excitatory glutamatergic transmission directly and/or indirectly from the PFC. Thus, tDCS stimulation of FPA, which sends projections to midbrain dopamine neurons, may affect dopamine cells in the SNc of PD patients. Furthermore, tDCS over the FPA might reorganize the functional connectivity of the M1 area through the dlPFC and nucleus accumbens (NAC). Red arrows indicate direct and/or indirect projections from the FPA, while blue arrows indicate dopamine projections.