- Card NS, Wairagkar M, Iacobacci C, Hou X, Singer-Clark T, Willett FR, Kunz EM, Fan C, Nia MV, Deo DR, Srinivasan A, Choi EY, Glasser MF, Hochberg LR, Henderson JM, Shahlaie K, Brandman DM, Stavisky SD. An accurate and rapidly calibrating speech neuroprosthesis. medRxiv [Preprint]. 2024 Apr 10:2023.12.26.23300110. doi: 10.1101/2023.12.26.23300110. Update in: N Engl J Med. 2024 Aug 15;391(7):609-618. doi: 10.1056/NEJMoa2314132. PMID: 38645254; PMCID: PMC11030484.
Neuroprosthetic communication in ALS
An article published in the NEJM presents new technologies that could restore communication in ALS: a breakthrough for paralysed patients.
A disease with no cure and a fatal outcome
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by the degeneration of motor neurons in the brain and spinal cord. This leads to muscle weakness, atrophy and eventually paralysis; most patients succumb to respiratory failure within 3-5 years after the onset of symptoms. Although cognitive functions often remain intact, the loss of motor skills, including speech, severely affects quality of life.
ALS affects about 2 in 100,000 people each year, with a slight male predominance. It typically manifests itself between the ages of 40 and 70. The disease can be sporadic or familial, with mutations in genes such as C9orf72, SOD1, TARDBP and FUS implicated in familial cases. Pathophysiology involves excitotoxicity, oxidative stress, mitochondrial dysfunction and neuroinflammation, all of which contribute to motor neuron degeneration. Clinically, ALS presents with asymmetric limb weakness, bulbar symptoms, spasticity and, in some cases, cognitive impairments associated with frontotemporal dementia.
An accurate and rapidly calibrating speech neuroprosthesis
A groundbreaking study published in the New England Journal of Medicine explores the potential of neuroprosthetic devices to restore communication in ALS patients with advanced motor impairment. The study focused on a patient with advanced ALS who had completely lost voluntary muscle control, including eye movements, rendering traditional assisted communication devices ineffective.
The researchers implemented an intracortical brain-computer interface (BCI), consisting of microelectrode arrays implanted in the motor cortex. This system recorded the neural signals associated with attempted movements and translated them into communication outputs. The study showed that despite the absence of overt motor function, the patient was able to modulate neural activity sufficiently to control the BCI, enabling basic communication.
The patient successfully used BCI to select letters and form words through a neurofeedback training process. Initially, the system required calibration to identify neural patterns corresponding to specific cognitive tasks. Over time, the patient improved in generating coherent neural signals, achieving a speed of communication that, although slow, allowed meaningful interaction with caregivers.
Key findings: preservation of cognitive functions without motor control
Importantly, the study showed that the cognitive functions necessary for communication remain intact even in the absence of physical movement. This finding supports the possibility that BCIs provide a viable communication channel for ALS patients in a state of complete blockade (CLIS), in which all voluntary muscle activity is lost.
In addition, the study reported that the patient was able to express personal needs and preferences, improving his sense of autonomy. The neuroprosthetic system demonstrated stable performance for several months, indicating its potential for long-term use. The researchers also emphasized the adaptability of the system, which could be fine-tuned to improve communication efficiency as the patient's needs evolve.
The successful use of neuroprosthetic devices in ALS represents a significant advance in patient care. It demonstrates that BCIs can bridge the communication gap for people who are otherwise unable to express themselves. This technology not only improves patients' quality of life, but also reduces the psychological burden on caregivers and families.
However, several challenges remain. Surgical implantation of microelectrode arrays involves risks, and the technology requires sophisticated equipment and skills. In addition, communication speed is limited compared to natural speech, highlighting the need for further technological refinements.
Future of non-invasive BCI technologies in ALS
The study opens up new ways for research into non-invasive or less invasive BCI systems with the aim of reducing surgical risks while maintaining effective communication capabilities. Advances in machine learning algorithms and neural signal processing should improve the accuracy and speed of BCIs.
Furthermore, the integration of BCIs with other assistive technologies could create hybrid systems that maximise communication efficiency. Ongoing clinical trials will be crucial to establish the safety, efficacy and long-term practicality of these devices in different patient populations. The recent NEJM study provides compelling evidence that neuroprosthetic devices can restore a degree of communication in ALS patients with complete motor paralysis.
This is a study on a single individual, so many more steps and further tests will be needed to confirm the effectiveness and safety of the device. It is not clear today whether the technical performance will be maintained as the disease progresses. However, it is a tool that, compared to previous versions, is extremely easy to use and impressively quick to learn. Moreover, the vocabulary achieved consists of almost all the words needed for an ordinary conversation and the error rate recorded is very low.
More research and development are essential to refine these systems and make them accessible to a broader range of patients, ultimately improving the quality of life for individuals affected by this devastating disease.
Rare Disease Day on 28 February 2025
Since 2008, the Rare Disease Day has been celebrated worldwide at the end of February. esanum covers the day and reports not only on current topics, but also on possible symptom complexes, diagnostics, therapeutic approaches and orphan drugs for the treatment of rare diseases.