Neural interface restores touch sensation after spinal cord injury 

A sensorimotor neural interface successfully restored touch sensation in a patient with quadriplegia resulting from a spinal cord injury, researchers report.

Dr Patrick D. Ganzer of Battelle Memorial Institute in Colombus, Ohio, said: “Neurotechnology and brain-computer interfaces are becoming an effective way to leverage residual neural signals for functional benefit following SCI, stroke, and several other dysfunctional states.”

An estimated 50% of patients with a clinically complete SCI have a “sensory discomplete” SCI, where tactile stimuli evoke changes in cortical activity, despite the patient not being able to feel them. Brain-computer interfaces (BCIs) can reanimate paralysed muscles after SCI, but whether they can restore touch is unknown.

Dr. Ganzer and colleagues used a BCI to simultaneously reanimate both motor function and touch sensation in a chronically paralysed patient with a clinically complete SCI who could already use a BCI to move the hand.

While the patient was unable to perceive mechanical sensory stimuli below spinal level C6, sensory stimuli to the hand robustly modulated neural activity in the contralateral primary motor cortex (M1). This residual sensory neural activity was reliably decoded from M1 using a support vector machine (SVM), and a vibrotactile array on the affected bicep enabled sensory feedback that restored conscious touch perception to a detection rate over 90%.

A modified grasp and release test demonstrated real-time sensorimotor demultiplexing where the participant was able to perform the task using the system but not without using the system, the team reports.

Discussing the study’s findings, Dr Ganzer said: “It was initially surprising when we first discovered the subperceptual touch signal.

“These results demonstrate that even a small contingent of spared spinal fibres can be leveraged for functional benefit.

“The study’s overall results are interesting because the brain implant was not originally intended to record both touch and movement neural signals.

“Participants that have a ‘clinically complete’ SCI may have a small contingent of spared fibres remaining that are still transmitting a neural signal. Therefore, a very small quantity of spared fibres can potentially be leveraged for benefit, even though they might only be transmitting a faint signal.

“Additionally, the study’s findings can potentially inform future neural implant locations. Future neural interfaces can be placed in areas that encode a multitude of mixed neural signals that might be of value for the given technology. Regardless, information from neural interfaces should be maximized to enable new functional benefits in patients, even in new and unintended ways.

“The NeuroLife team at Battelle is currently working with our collaborators to develop a take-home BCI system. This would allow for the BCI to be used during activities of daily living outside of the laboratory setting.

“One of our recent achievements in this domain was a demonstration in the participant’s home using a portable miniatured version of the ‘muscle stimulation system.’ A computer tablet was able to control muscle stimulation to elicit hand movements during home activities.”

Dr Andrew Jackson, professor of neural interfaces at Newcastle University, Newcastle-upon-Tyne told Reuters Health: “The study rests on a surprising finding: touch stimuli that are imperceptible to a spinal cord-injured participant can nevertheless be ‘decoded’ from brain activity in the motor cortex. Previous brain imaging studies have suggested such signals can reach the brain even after injury, but this is the first study to reveal them in the activity of individual brain cells.

“There are two ways this could work in practice. First, the decoded sensory signals could be used to trigger some kind of sensory substitute, in this case a vibrotactile cuff acting on a part of the body that the patient can consciously feel.

“Second, the sensory signals could directly influence the electrical muscle stimulation, thereby implementing a sensorimotor feedback loop similar to the unconscious reflexes that allow us to maintain our grip on an object without having to think about it.

“While there are other ways to achieve this in principle, the nice thing about the current approach is that it only requires a single surgical implant to achieve both motor and sensory restoration.

“These approaches are still at an early stage of development. I anticipate seeing more studies like this one that find clever ways of exploiting and enhancing these surviving connections to restore function.”

Scientists regenerate neurons in mice with spinal cord injury and optic nerve damage

New research by scientists at the Lewis Katz School of Medicine Temple University (LKSOM) shows that gains in functional recovery from SCI injuries may be possible, thanks to a molecule known as Lin28, which regulates cell growth. In a study published online in the journal Molecular Therapy, the Temple researchers describe the ability of Lin28 – when expressed above its usual levels – to fuel axon regrowth in mice with SCI or optic nerve injury (ONI), enabling repair of the body’s communication grid.

Shuxin Li, senior investigator on the new study, explained: “Our findings show that Lin28 is a major regulator of axon regeneration and a promising therapeutic target for central nervous system injuries.

“We became interested in Lin28 as a target for neuron regeneration because it acts as a gatekeeper of stem cell activity. It controls the switch that maintains stem cells or allows them to differentiate and potentially contribute to activities such as axon regeneration.”

To explore the effects of Lin28 on axon regrowth, Dr Li and colleagues developed a mouse model in which animals expressed extra Lin28 in some of their tissues. When full-grown, the animals were divided into groups that sustained spinal cord injury or injury to the optic nerve tracts that connect to the retina in the eye.

Another set of adult mice, with normal Lin28 expression and similar injuries, were given injections of a viral vector (a type of carrier) for Lin28 to examine the molecule’s direct effects on tissue repair.

Extra Lin28 stimulated long-distance axon regeneration in all instances, though the most dramatic effects were observed following post-injury injection of Lin28. In mice with spinal cord injury, Lin28 injection resulted in the growth of axons to more than three millimetres beyond the area of axon damage, while in animals with optic nerve injury, axons regrew the entire length of the optic nerve tract. Evaluation of walking and sensory abilities after Lin28 treatment revealed significant improvements in coordination and sensation.

“We observed a lot of axon regrowth, which could be very significant clinically, since there currently are no regenerative treatments for spinal cord injury or optic nerve injury,” said Dr Li.

One of his goals in the near-term is to identify a safe and effective way of getting Lin28 to injured tissues in human patients. To do so, his team of researchers will need to develop a vector, or carrier system for Lin28, that can be injected systemically and then hone in on injured axons to deliver the therapy directly to multiple populations of damaged neurons.

Dr Li also wants to decipher the molecular details of the Lin28 signalling pathway. He said: “Lin28 associates closely with other growth signaling molecules, and we suspect it uses multiple pathways to regulate cell growth.”

‘Cell pores’ discovery gives hope to millions of brain and spinal cord injury patients

Brain and spinal cord injuries affect all age groups. Older people are more at risk of sustaining them from strokes or falls, while for younger age groups, major causes include road traffic accidents and injuries from sports.

The high-profile example of Formula 1 racing driver Michael Schumacher demonstrates the difficulties physicians currently face in treating such injuries. After falling and hitting his head on a rock while skiing in Switzerland in 2013, Schumacher developed a swelling on his brain from water rushing into the affected cells. He spent six months in a medically induced coma and underwent complex surgery, but his rehabilitation continues to this day.

The new treatment, developed by an international team of scientists working at universities in the UK, US, Canada, Sweden and Denmark, features in the latest edition of the scientific journal Cell.

Researchers used an already-licensed anti-psychotic medicine – trifluoperazine (TFP) – to alter the behaviour of tiny water channel ‘pores’ in cells known as aquaporins.

Testing the treatment on injured rats, they found those animals given a single dose of the drug at the trauma site recovered full movement and sensitivity in as little as two weeks, compared to an untreated group that continued to show motor and sensory impairment beyond six weeks after the injury. 

The treatment works by counteracting the cells’ normal reaction to a loss of oxygen in the CNS – the brain and spinal cord – caused by trauma. Under such conditions, cells quickly become ‘saltier’ because of a build-up of ions, causing a rush of water through the aquaporins which makes the cells swell and exerts pressure on the skull and spine. This build-up of pressure damages fragile brain and spinal cord tissues, disrupting the flow of electrical signals from the brain to the body and vice versa.  

However, the scientists discovered that TFP can stop this from happening. Focusing their efforts on important star-shaped brain and spinal cord cells called astrocytes, they found TFP prevents a protein called calmodulin from binding with the aquaporins. Normally, this binding effect sends the aquaporins shooting to the surface of the cell, letting in more water. By halting this action, the permeability of the cells is reduced.

Traditionally, TFP has been used to treat patients with schizophrenia and other mental health conditions. Its long-term use is associated with adverse side effects, but the researchers said their experiments suggested that just a single dose could have a significant long-lasting impact for CNS patients.

Since TFP is already licensed for use in humans by the US Federal Drug Administration (FDA) and UK National Institute for Health and Care Excellence (NICE) it could be rapidly deployed as a treatment for brain injuries. But the researchers stressed that further work would allow them to develop new, even better medicines based on their understanding of TFP’s properties.

According to the World Health Organisation (WHO), each year around 60 million people sustain a traumatic brain or spinal cord injury and a further 15 million people suffer a stroke. These injuries can be fatal or lead to long-term disability, psychiatric disorders, substance abuse or self-harm.

Professor Roslyn Bill of the Biosciences Research Group at Aston University said: “Every year, millions of people of all ages suffer brain and spinal injuries, whether from falls, accidents, road traffic collisions, sports injuries or stroke. To date, their treatment options have been very limited and, in many cases, very risky.

“This discovery, based on a new understanding of how our cells work at the molecular level, gives injury victims and their doctors hope. By using a drug already licensed for human use, we have shown how it is possible to stop the swelling and pressure build-up in the CNS that is responsible for long-term harm.

“While further research will help us to refine our understanding, the exciting thing is that doctors could soon have an effective, non-invasive way of helping brain and spinal cord injury patients at their disposal.”

Dr Zubair Ahmed of the University of Birmingham’s Institute of Inflammation and Ageing continued: “This is a significant advance from current therapies, which only treat the symptoms of brain and spinal injuries but do nothing to prevent the neurological deficits that usually occur as a result of swelling. The re-purposed drug offers a real solution to these patients and can be fast-tracked to the clinic.”

Dr Alex Conner of the University of Birmingham’s Institute of Clinical Sciences said: “It is amazing that our work studying tiny water channels in the brain can tell us something about traumatic brain swelling that affects millions of people every year.”

Dr Mootaz Salman, Research Fellow in Cell Biology at Harvard Medical School, said: “This novel treatment offers new hope for patients with CNS injuries and has huge therapeutic potential. Our findings suggest it could be ready for clinical application at a low cost in the very near future”.

Brain-computer interface lets man with complete spinal cord injury feel and move his hand

In an exciting development, researchers from Battelle and The Ohio State University Wexner Medical Center are reporting that a man with clinically complete spinal cord injury can now move his paralysed hand and feel what he’s touching.

The man had a brain-computer interface chip implanted into the motor cortex of his brain six years ago and it was assumed that his injury was too severe to ever be able to tap the nerve signals related to touch.

However, the latest update reports an unfelt signal that was detected by the researchers, which does reach the brain via unexpected pathways, and which they can detect using the brain-computer interface. In turn, the signal is translated and directed to a haptic device that creates a vibration that produces a sense of touch. The development is reported in a published study in journal Cell.

The team that developed the technology is working on turning it into a system that can be used at home, as it is currently tethered to power supplies and computers.

“The authors have leveraged on a rarely appreciated aspect of spinal cord injury to provide a novel and important advancement in neurological functioning using a brain-computer interface,” said Dr Keith Tansey, Professor of Neurosurgery and Neurobiology at the University of Mississippi Medical Center.

“The notion that clinical completeness in spinal cord injury is very often neurophysiologically ‘discomplete’ acknowledges that activity in residual neural circuitry can be detected and utilised to both augment motor function but also to restore sensory perception from below the level of injury.”

Adults with traumatic spinal cord injury at increased risk for psychological morbidities, study suggests

Adults with traumatic spinal cord injuries (SCI) exhibited increased incidence of psychological morbidities and multimorbidity compared with those without such injuries, according to results of a study published in Mayo Clinic Proceedings.

Mark D Peterson of the department of physical medicine and rehabilitation at University of Michigan said: “Clinicians caring for adults with SCI need to be aware of the increased risk of developing mental health disorders in this patient population.

“This may be particularly important during social distancing due to Covid-19, as these patients often already experience social isolation.”

Although prior studies have established a relationship between age-related noncommunicable diseases, cognitive dysfunction and depression among populations without SCI, researchers have yet to study the extent to which psychological conditions are comorbid with age-related chronic diseases following SCI.

Further research is sparse regarding the natural history or incidence of psychological morbidities and chronic diseases among adults with SCI.

In the current study, the investigators sought to compare the longitudinal incidence of psychological morbidities and multimorbidity and chronic disease estimates among adults with vs. without SCI. They examined insurance claims of 6,847 privately insured beneficiaries with an ICD-9, Clinical Modification diagnostic code for a traumatic spinal cord injury who had medical coverage at any time between January 2001 and December 2017.

Results showed that compared with adults without a traumatic SCI, those with one had a higher incidence of adjustment reaction, anxiety disorders, depressive disorders, alcohol dependence, drug dependence, psychogenic pain, dementia, insomnia and psychological multimorbidity.

For example, incidence for those with vs. without a traumatic SCI was 19.3% vs. 14.1% for anxiety disorders, 29.3% vs. 9.3% for depressive disorders and 37.4% vs. 23.9% for psychological multimorbidity. The researchers reported significantly higher adjusted HRs of each psychological outcome for individuals with spinal cord injury, and these ranged from 1.18 (95% CI, 1.08-1.29) for anxiety disorders to 3.32 (95% CI, 1.93-5.71) for psychogenic pain.

Those with spinal cord injuries also had a significantly higher prevalence of all chronic diseases and chronic disease multimorbidity, except HIV infection/AIDS. The researcher’s propensity matched adults for age, education, race, sex and chronic diseases and still reported a significantly higher incidence of most psychological disorders and psychological multimorbidity among those with spinal cord injuries.

Of the findings, Peterson and colleagues said: “Future research and clinical efforts are needed to better understand the health care burden associated with these conditions in the traumatic [spinal cord injury] population.

“These findings should be used to inform the development of appropriate clinical screening algorithms and design of early behavioural interventions to reduce the risk for disease onset/progression in this higher risk population.”