Currently, there are few pharmacological treatments that effectively and comprehensively address the symptoms of PD [14]. These treatments only target the motor symptoms, while non-motor symptoms such as cognition remain unaffected and continue to negatively impact the quality of life of patients [15, 16, 17]. Consequently, the possibility of resorting to non-pharmacological treatments, including non-invasive brain stimulation (NIBS) targeting affected cortical areas, has been considered [18, 19, 20]. Among these, transcranial direct current stimulation (tDCS) could promote synaptic plasticity and reinforce compensatory brain networks [21, 22, 23]. It involves a method of non-invasive neurostimulation through a low-intensity electric current applied to the scalp’s surface using one or two stimulation electrodes positioned over specific brain regions [24, 25, 26, 27]. The direction and intensity of the current influence neuronal activity. Anodal stimulation increases the excitability of brain areas near the electrode, while cathodal stimulation decreases it [28, 29]. The short-term effects of tDCS are caused by depolarization of the membrane potential, while the long-term effects are linked to mechanisms involving N-methyl-D-aspartate (NMDA) receptors and synaptic plasticity [30, 31]. Despite possible adverse effects, such as tingling, itching, mild headache, and skin burns, tDCS is generally considered a safe rehabilitative strategy that offers several advantages, including painless application, few side effects, cost-effectiveness, and the potential for at-home administration with remote expert supervision [32, 33, 34]. As a result, tDCS has been adopted with significant success, demonstrating promising results in addressing brain degenerative processes, encompassing both physiological processes related to aging and pathological processes, covering a wide range of neurological disorders [35, 36, 37, 38] and neuropsychiatric conditions [39, 40, 41, 42]. The application of tDCS has raised new prospects for the treatment of mild cognitive impairments and dementia [43, 44, 45, 46]. tDCS appears to be particularly effective in cases of mild cognitive impairment, showing more promising results compared with its application in Alzheimer’s dementia [47]. Therefore, the use of tDCS should be considered during the phase of PD-MCI, when effectiveness seems particularly likely [48]. Considering all this, there is a growing need for randomized placebo-controlled trials that assess both the efficacy and specific neural mechanisms of the exclusive use of tDCS in individuals affected by PD-MCI. Despite the established evidence for tDCS, conflicting results have emerged from studies examining the effects of tDCS in combination with other treatments [49, 50, 51]. These studies have reported improvements in various cognitive domains, but whether these improvements can be solely attributed to tDCS or whether there has been adjunct effect—an enhancement of the effects of additional therapies—remains ambiguous [52, 53, 54, 55]. This point is of considerable significance and requires further investigation.

Cognitive deficits in PD encompass various aspects, including executive functions, visuospatial abilities, and memory [10, 11]. Event-related potentials (ERPs) represent an objective quantifier of cognitive functions, providing an opportunity to monitor cognitive changes without the apparent influence of motor deficits in PD [56]. ERPs are a valuable tool in cognitive neuroscience that allow researchers to measure and analyze brain activity in response to specific stimuli or events. ERPs are obtained through electroencephalography (EEG), a non-invasive technique that records the electrical activity of the brain over time. EEG involves placing electrodes on the scalp, which detect and record electrical signals generated by neural activity. ERPs are time-locked to a specific event, such as the presentation of a stimulus, and provide a way to assess neural processing associated with sensory, motor, or cognitive functions. In our study, the P300 ERP is of particular importance [57]. The P300 component is a positive deflection in the ERP waveform that typically occurs around 300 ms after the presentation of a rare or unexpected stimulus. P300 is associated with cognitive processes related to attention, memory, and decision-making. The onset latency of the P300 component, which is the time it takes for the P300 response to appear after a stimulus, is an essential measure as it reflects the speed and efficiency of cognitive processing. In addition to ERPs, the present study investigated the role of alpha and beta band rhythms in PD. These neural oscillations, measured through EEG, are critical in understanding the motor and cognitive aspects of PD. The alpha band is associated with the inhibition of sensory information processing. When the brain is at rest or not engaged in a specific cognitive task, alpha rhythms are dominant. They are typically recorded over posterior brain regions and are believed to be involved in inhibiting irrelevant sensory information, thereby promoting focused attention and cognitive stability. Beta rhythms are associated with motor control and motor planning. They are often recorded over motor-related areas of the brain, such as the sensorimotor cortex. These rhythms are implicated in the coordination of muscle movements, and their modulation is linked to changes in motor function [58]. In PD, aberrations in alpha and beta band rhythms, coupled with alterations in P300 oscillatory dynamics, may collectively serve as critical neurophysiological markers. These markers potentially underlie the intricate interplay observed between motor dysfunction and cognitive impairment in individuals with PD [59]. The rationale for their utilization lies in the well-established involvement of alpha and beta band rhythms in motor control, as evidenced by Hammond et al. [59], which is closely intertwined with the cognitive deficits witnessed in PD. Concurrently, abnormalities in P300 oscillations have been linked to cognitive decline in PD [60]. Consequently, we posit that investigating the convergence of alpha and beta band rhythms with P300 oscillations in PD could illuminate the mechanistic underpinnings of both the motor and cognitive manifestations of the disease.

Although a body of evidence suggests that ERPs could be a sensitive method to investigate mechanisms of symptomatic improvement due to tDCS [61], and while some studies have investigated the neurophysiological effects of tDCS in samples with mild cognitive decline [62, 63], few studies have investigated the effects of tDCS on ERPs in PD [64, 65, 66, 67, 68]. The primary objective of this research was to assess the effects of tDCS on the left dorsolateral prefrontal cortex (DLPFC) in patients with PD concerning neurophysiological functions measured through EEG. Our hypothesis posited that tDCS on the left DLPFC would lead to a reduction in the onset latency of the P300 event-related potential, accompanied by an increase in alpha and beta band rhythms within the neural oscillatory activity. This hypothesis is grounded in prior research findings that have demonstrated the modulatory effects of tDCS on cortical excitability and neural oscillations [69, 70, 71]. Specifically, studies have shown that tDCS can influence neuronal membrane potentials and enhance cortical synchronization, which are associated with alterations in event-related potentials and alpha and beta band rhythms. Furthermore, the left DLPFC is a region known to be involved in the cognitive processes of interest, including those related to P300 latency [72, 73]. Preliminary studies and research on deep brain stimulation (DBS) in PD have suggested that modulating the left DLPFC could lead to improvements in both motor and cognitive symptoms [74]. These prior findings have justified further investigation into DLPFC stimulation in the context of PD. In fact, the left DLPFC is implicated in high-level cognitive functions such as attention, working memory, and decision-making [75]. Cognitive deficits are common in PD [76]. Stimulating the left DLPFC may potentially enhance these compromised cognitive functions. Stimulation of the left DLPFC may have a dual effect, improving both motor and cognitive symptoms because this brain region is involved in both types of functions [14, 77]. DLPFC stimulation can influence brain circuits, including those connecting the DLPFC to other brain regions involved in PD symptoms. This modulation may help regulate brain activity and enhance function in affected areas. Furthermore, in this study, we hypothesized that (a) patients undergoing tDCS would exhibit a significant reduction in the onset latency of the P300 event-related potential compared with the group undergoing sham tDCS and (b) patients undergoing tDCS would demonstrate a significant increase in the power spectrum of alpha and beta band rhythms compared with the group undergoing sham tDCS.

The study employed an ABA experimental design, consisting of a pre-test, an intervention, and a post-test or both groups. It was double-blinded, on the part of both the researcher and the evaluator. A matching procedure was implemented for the assignment. The tDCS group was initially recruited and, subsequently, the sham group was matched to them based on key demographic and clinical variables, ensuring baseline comparability between the two groups. This approach was chosen to minimize potential confounding factors and enhance the internal validity of our study.

Based on the sample size commonly reported in the literature and the estimated sample dimension [78, 79], 30 patients diagnosed with PD were recruited from the Madonna della Consolazione Polyclinic Nursing Home in Reggio Calabria, a region in Southern Italy. All participants were aged between 67 and 82 years (mean age [M] = 74.5 years, standard deviation [SD] = 7.2 years). Among these patients, a group of 15 individuals received anodal tDCS, while the other group of 15 age- and sex-matched subjects received simulated tDCS.

Inclusion criteria required a diagnosis of PD based on the guidelines of the United Kingdom Parkinson’s Disease Society (UKPDS) and the clinical diagnostic criteria of the Brain Bank [80, 81]. Additionally, the diagnosis of PD-MCI aligned with Level 2 (comprehensive) criteria for PD-MCI [82], which involved a performance that was 1.5 SDs below normative data in at least two tests within a single domain or in one or two tests across distinct domains [83]. Selected participants exhibited scores ranging from 22 to 26 points on the Mini-Mental State Examination (MMSE), which was adjusted for the educational level of this population [84, 85]. The clinical data related to the Unified Parkinson’s Disease Rating Scale (UPDRS) [86] of patients who underwent anodal tDCS and sham procedure were extracted from medical records. Furthermore, a detailed clinical assessment of the patients was conducted, and they presented motor symptoms ranging from stage I to III on the Hoehn and Yahr (H&Y) scale [87]. Right-hand laterality was assessed using the Edinburgh Handedness Inventory (EHI). All patients had been maintained on stable and optimal dopaminergic medication therapy for at least one month prior to the start of the study and were required to maintain this regimen throughout the study’s duration.

Exclusion criteria included a diagnosis or evidence of secondary or atypical parkinsonism, previous clinically significant neurological disorders, prior neurosurgical interventions, head traumas, brain injuries, epilepsy, stroke, or multiple sclerosis. Additionally, patients with a diagnosis of major depressive disorder, psychotic disorders, bipolar disorder, or alcohol and substance use disorders were excluded.

This study was conducted in accordance with the Declaration of Helsinki and received approval from the Ethics Committee of Madonna della Consolazione Polyclinic Nursing Home (protocol approval number 2021-198). Clinically documented data, already available at the healthcare facility and provided by healthcare professionals within a timeframe not exceeding one month (MMSE, UPDRS, DD [Duration of Disease], LEV [Levodopa Equivalent Dose], H&Y score), were utilized for the present study. Before participating, each participant received detailed information about the study’s purpose and data collection procedures. This information was presented clearly and comprehensibly, enabling participants to make an informed decision about their involvement. Subsequently, each participant provided written informed consent. Prior to the intervention, participants were thoroughly briefed on the stimulation procedure employed in the study. This explanation included details about the functioning of tDCS, as well as the associated practical procedures. Additionally, a clear illustration of potential side effects related to the intervention was provided. Each participant was informed of their right to withdraw from the study at any time without incurring any negative consequences. At the start of the stimulation, participants were asked about their tolerance to the 2 mA or if they experienced any discomfort. Subjects tolerated the treatment well, and no adverse effects associated with tDCS were observed.

In this research, the electroencephalogram was employed as the measuring instrument to explore neurophysiological parameters. More precisely, the analysis focused on the P300 component through an auditory oddball paradigm, while also examining the rhythms within the alpha and beta bands from the DLPFC.

The tDCS device utilized in this study was the BRAINDEE stimulator, manufactured by Omicron-t S.r.l., based in Naples, Italy. Stimulation was conducted using a pair of sponge electrodes, each with a diameter of 25 mm, previously saturated with a saline solution. A constant current was delivered by a battery-powered stimulator. The decision was made to target the left DLPFC due to its involvement in high-level cognitive functions such as attention, working memory, and decision-making. These cognitive functions are frequently impaired in patients with PD. By modulating the DLPFC, this stimulation may contribute to improvements in both motor and cognitive symptoms. Given the DLPFC’s dual role in motor and cognitive functions, stimulating this region could potentially have a dual effect, enhancing compromised cognitive functions as well [92, 93]. To activate the left DLPFC, the anode was positioned over the F7 region, while the cathodic reference electrode was located above the right supraorbital area. The precise electrode placement was determined following the EEG 10–20 system. Stimulation intensity was set at 2 mA (with a current density of 2.5 mA/cm${}^2$) for 20 minutes, administered five times a week for two consecutive weeks, both in the study group and the placebo group. The decision to use 2 mA was based on the safety and comfort of our participants. We opted for the 2 mA intensity as it is considered safe and well-tolerated, which is particularly crucial when dealing with individuals who may have various health conditions or sensitivities. Safety is paramount in human research, and a 2 mA intensity level is widely accepted [79, 94].

In the simulated sham condition, the electrodes were placed in the same manner as in actual stimulation, but the stimulation automatically ceased after 10 s from the beginning of the session. This time interval is insufficient to induce a significant stimulation effect on the brain. A stimulation ramp was incorporated to ensure that participants would experience the typical tingling sensations near the electrodes, creating the illusion of receiving stimulation even during the simulated sham condition when no actual stimulation was applied. This procedure was implemented to maintain participants’ unawareness of whether they were receiving real stimulation or the sham condition.

All statistical analyses were conducted using SPSS 24.0 software (SPSS Inc., Chicago, IL, USA). The main objective of the analyses was to explore potential differences between the experimental group (i.e., anodal stimulation) and the sham group (i.e., sham stimulation) in neurophysiological parameters such as P300 latency and the alpha and beta band rhythms. To verify the causal relationship between UPDRS as a predictive variable and the P300 latency and the alpha and beta band rhythms, separate linear regressions were conducted. Repeated-measures (RM) analysis of variances (ANOVAs) were performed, employing the experimental groups as a between-subjects factor, and the phases—pre- and post-tests—as within-subjects factors. Furthermore, if the RM ANOVAs revealed significance, a post hoc analysis was conducted to identify which group exhibited changes between the pre- and post-test phases. Post hoc pairwise comparisons were executed using the Student’s paired t-test. To address the issue of multiple comparisons, significance was attributed solely to the level p 0.005. Regarding effect size, we employed Cohen’s d for t-test comparisons, Eta-squared ($\eta$${}^2$) for ANOVA, and R-squared (R${}^2$) for regression analysis.