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Maggio, M.G.; Billeri, L.; Cardile, D.; Quartarone, A.; Calabrò, R.S. Innovation Technology for Huntington’s Disease Rehabilitation. Encyclopedia. Available online: (accessed on 17 June 2024).
Maggio MG, Billeri L, Cardile D, Quartarone A, Calabrò RS. Innovation Technology for Huntington’s Disease Rehabilitation. Encyclopedia. Available at: Accessed June 17, 2024.
Maggio, Maria Grazia, Luana Billeri, Davide Cardile, Angelo Quartarone, Rocco Salvatore Calabrò. "Innovation Technology for Huntington’s Disease Rehabilitation" Encyclopedia, (accessed June 17, 2024).
Maggio, M.G., Billeri, L., Cardile, D., Quartarone, A., & Calabrò, R.S. (2024, January 16). Innovation Technology for Huntington’s Disease Rehabilitation. In Encyclopedia.
Maggio, Maria Grazia, et al. "Innovation Technology for Huntington’s Disease Rehabilitation." Encyclopedia. Web. 16 January, 2024.
Innovation Technology for Huntington’s Disease Rehabilitation

Huntington’s disease is an autosomal dominant neurodegenerative disease caused by the repetition of cytosine, adenine, and guanine trinucleotides on the short arm of chromosome 4p16.3 within the Huntingtin gene. Given the considerable impact the disease has on the patient’s personal, relational, and psychophysical sphere, rehabilitation approaches are an excellent option to treat these patients. 

Huntington’s disease neurorehabilitation cognitive rehabilitation virtual reality NIBS physical therapy

1. Introduction

Huntington’s disease (HD), an autosomal dominant neurodegenerative disease, is caused by the repetition of cytosine, adenine, and guanine trinucleotides on the short arm of chromosome 4p16.3 within the Huntingtin gene [1][2]. This disease generally affects individuals between the age of 30 and 50, but it can also manifest before the age of 20 as juvenile HD, which is characterized by learning difficulties and behavioral disorders at school [3]. HD diagnosis is mainly clinical, based on the observation of motor and/or cognitive and behavioral disorders in individuals with a family history of the disease, and is confirmed through DNA testing [4]. Unfortunately, there is currently no cure for the disease, and treatment focuses on managing symptoms and complications (such as pneumonia and suicide attempts) and improving the quality of life [5][6]. The latter, in fact, resulted to be strongly impacted by motor, cognitive, and psychiatric disorders related to HD. Involuntary choreic movements along with cognitive and behavioral disturbances constitute pathognomonic symptoms of pathology [7][8][9][10]. Specifically, the most common motor disorders involve involuntary movements that begin in the distal extremities, including the facial muscles, and then gradually progress to the more proximal and axial muscles, increasing in amplitude [7][8]. Over time, motor symptoms progressively worsen and may include hypokinesia with bradykinesia, dystonia, rigidity, and extremity contractures. Additionally, dysarthria and dysphagia, dystonia, tics, and cerebellar signs, such as ataxia, may occur. As for behavioral and psychiatric symptoms, they often precede motor symptoms and resemble frontal lobe dysfunction, with poor attention, impulsiveness, and irritability [10][11]. Other possible symptoms include apathy, loss of intuition and creativity, psychosis, lack of awareness, and depression, often associated with suicide attempts [11][12]. Cognitive difficulties are frequently present in HD, affecting executive functions related to organization, multitasking, and planning [13], sometimes resembling subcortical dementia with memory loss [13].
Given the considerable impact the disease has on the patient’s personal, relational, and psychophysical sphere, rehabilitation approaches are an excellent option to treat these patients. The term rehabilitation refers to a multidisciplinary approach aimed at restoring or enhancing an individual’s ability to live independently and participate fully in society following an injury, illness, or disability [14]. It encompasses various traditional approaches, including physical therapy, occupational therapy, speech therapy, and neuropsychology. However, the use of new rehabilitation technologies, such as virtual reality (VR), Pc-Based training, or innovative techniques, such as non-invasive brain stimulation (NIBS), could make a significant contribution to improving functional outcomes, as seen in other conditions [15][16][17][18].

2. Innovative Rehabilitation Devices

2.1. Virtual Reality

Virtual Reality (VR) is a multisensory and interactive simulation of ecological scenarios. These scenarios are typically three-dimensional, replicating objects and events to provide the users with the illusion of active interaction with the screen [19]. Additionally, VR provides audiovisual feedback in response to the subject’s movements. Due to its characteristics, VR has the potential to enhance motor and cognitive functions as well as improve well-being and treatment compliance [20]. VR experiences allow for patients to be at the center of the implemented programs, thanks to the high level of training customization [21]. Furthermore, two key concepts related to VR are immersion and presence. Immersion represents the objective sense of sensory absorption/immersion in the computer-generated, three-dimensional environment. This process is connected to the concept of presence, with a subjective psychological state in which the user is consciously engaged in the virtual context. From this perspective, VR could be highly beneficial in the treatment of cognitive, emotional, and motor disorders in HD patients.
The VR devices used in the reviewed studies differ significantly. Some devices promote daily life skills, as seen in RCT conducted by Begeti et al. [22]. The authors utilized a VR tool where patients swim in a pool using a joystick, with the task of reaching a submerged platform guided by external cues. Similarly, Julio et al. used a VR device, namely “EcoKitchen”, which enhances the executive functions necessary for simple daily tasks, such as making toast or a cup of coffee with milk, or simple actions, such as removing a kettle from heat. This highlights the potential role of VR in increasing task execution awareness [23]. Two other studies by the same authors emphasized that the “EcoKitchen” can detect executive deficits in patients with early and premanifest HD and is feasible [24][25]. Lastly, Cellini et al., in a single case study, evaluated the effectiveness of the Computer Assisted Rehabilitation Environment (CAREN), an immersive VR tool, in the rehabilitation of an HD patient, observing the potential role of VR devices in improving motor outcomes [26].

2.2. PC-Based Rehabilitation

PC-based methods involve the use of software to implement intensive, targeted, and repeated interventions for specific cognitive and motor functions. These interventions typically include the execution of tasks or games, often referred to as ‘serious games’, that involve various domains [26]. The primary goal of this method is to enhance performance by utilizing positive reinforcement, which includes providing sensory and motivational feedback [27]. Additionally, these exercises offer therapists the flexibility to adjust the duration and difficulty of the tasks to match the individual’s characteristics and needs [27][28]
Kempnich et al., in an RCT using a computerized program known as the MicroExpression Training Tool, found that emotion recognition training has proven promising in maintaining participant engagement [29]. Another RCT by Kloos et al. demonstrates the feasibility and effectiveness of a PC game called “Dance Dance Revolution” in patients with HD for enhancing motor skills [30]. In this context, Yhnell et al. observed that the Cogmed computer program, designed for cognitive and motor improvement, is well-received and feasible for individuals with HD [31]. The same tool has been used by Sadeghi et al. to enhance working memory with positive results [32]. On the other hand, Coulson et al. conducted a study on the messages exchanged by patients in online chats, noting that social support provided through online IT platforms plays a crucial role in patients with HD [33]. Moreover, some researchers have also emphasized the importance of multidisciplinary treatments, in which PC-based methods were included. Bartlett et al. showed that subjecting individuals with HD to a multidisciplinary intervention, including computerized training, leads to significant improvements in verbal learning, memory, attention, cognitive flexibility, and processing speed compared to conventional treatment [34]. Indeed, another study by the same authors showed that multidisciplinary rehabilitation, including PC-based approaches, can mitigate hypothalamic volume loss and sustain peripheral BDNF levels in preclinical HD individuals, improving cognitive functions [35]. Finally, Metzler-Baddeley et al. conducted a web-based survey, demonstrating that tablet-based touch screens were recognized as feasible and accessible solutions for rehabilitation with a PC app [36].

3. Other Therapy (Cognitive and Motor Rehabilitation)

Most studies in the literature encourage the use of physical rehabilitation, either performed individually or as part of a multidisciplinary approach, to promote improvements in the physical and cognitive outcomes of HD patients [37][38][39][40][41]. Among various interventions, researchers have selected some articles that presented motor and cognitive therapies implemented with innovative technology (Table 1). In this context, Khalil et al. have focused on improving home-based rehabilitation with physical exercises using an exercise DVD [42]. The authors found that structured, short-term home exercise programs are practical, beneficial, and safe for individuals in the early and middle stages of HD [42].
Furthermore, Shih et al. employed a four-month coaching program in which participants utilized Fitbit devices and received support through a behavioral intervention aimed at promoting the physical activity, showing the effectiveness of this device [43].
Finally, another type of intervention with promising results is dance therapy. A study by Trinkel et al. on HD patients showed promising results in terms of spatial and bodily representations, helping to enhance motor function in individuals with HD [44].
Table 1. The main studies regarding other interventions in Huntington’s disease.

4. Non-Invasive Brain Stimulation (NIBS)

Recent studies explored alterations in interhemispheric connectivity in HD and its temporal association with clinical manifestations. The prevailing understanding of motor symptoms in HD attributes them to a disorganized sensory–motor network and disrupted neurotransmission between the motor cortex and basal ganglia [45][46][47].
The use of neuromodulation techniques for managing HD-related symptoms has been FDA-approved, although their application remains primarily in the research contexts. However, growing interest surrounds non-invasive neuromodulation methods, including transcranial magnetic stimulation (TMS), transcranial electric stimulation (tES), and particularly transcranial direct current stimulation (tDCS), as potential therapies for neurodegenerative diseases, such as HD [48]. A recent systematic review highlights abnormal brain connectivity in various networks in HD, including sensory, motor, visual, and executive/attentional networks [49]. Non-invasive neuromodulation methods are believed to work by reorganizing brain networks, potentially rectifying the aberrant connectivity observed in HD, thereby positively influencing associated symptoms. While the initial studies suggest the effectiveness of these methods with minimal side effects, the evidence remains limited [50].

5. tDCS

The utility of transcranial electric stimulation (tES) in movement disorders has proven promising, but its mainstream application remains limited, primarily due to the diversity of patient populations and protocols [51][52]. Transcranial direct current stimulation (tDCS), combined with cognitive tasks, has shown the potential to enhance cognitive functioning, which is particularly relevant in HD, given its progressive cognitive impairment [51][52]. Two double-blinded crossover trials with tDCS have demonstrated improvements in cognitive and motor symptoms in HD, although further research is needed to understand the full extent of these effects [51][52].

6. TMS

Repetitive transcranial magnetic stimulation (rTMS) has been employed to alleviate choreiform movements in HD patients. Five studies have utilized TMS for HD [53][54][55][56][57]. These studies used different TMS modalities and coil types, targeting various brain regions. The studies reported symptom improvements, with some variations in the results likely due to different factors, including target accuracy, coil size, and pulse parameters. However, the duration of improvement, in some cases, was temporary.

7. tACS

Transcranial alternating current stimulation (tACS) is a versatile non-invasive brain stimulation (NIBS) technique that can target specific neural oscillatory frequencies, showing minimal and transient adverse effects [57][58]. Recent research has indicated that alpha frequency tACS, targeting bilateral mPFC (medial prefrontal cortex), has the potential to influence brain activity in HD patients. In summary, neuromodulation techniques, such as TMS, tDCS, and tACS, show promise in ameliorating the symptoms and connectivity issues associated with HD, but further research is necessary to better understand their efficacy and potential applications [59].
A summary of the main characteristics of studies regarding NIBS in HD patients can be found in Table 2.
Table 2. The main studies regarding NIBS in Huntington’s disease.


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