Hitting the target with non-invasive deep brain stimulation: Potential therapy for addiction, depression, and OCD

Researchers at EPFL have successfully tested a novel technique for probing deep into the human brain, without surgery, for potential therapeutic purposes.

Non-invasive stimulation of the striatum

A model image of the targeted deep brain zone, the striatum, a key player in reward and reinforcement mechanisms. CREDIT EPFL

Neurological disorders, such as addiction, depression, and obsessive-compulsive disorder (OCD), affect millions of people worldwide and are often characterized by complex pathologies involving multiple brain regions and circuits. These conditions are notoriously difficult to treat due to the intricate and poorly understood nature of brain functions and the challenge of delivering therapies to deep brain structures without invasive procedures.



In the rapidly evolving field of neuroscience, non-invasive brain stimulation is a new hope for understanding and treating a myriad of neurological and psychiatric conditions without surgical intervention or implants. Researchers, led by Friedhelm Hummel, who holds the Defitchech Chair of Clinical Neuroengineering at EPFL’s School of Life Sciences, and postdoc Pierre Vassiliadis, are pioneering a new approach in the field, opening frontiers in treating conditions like addiction and depression.

Their research, leveraging transcranial Temporal Interference Electric Stimulation (TMS), specifically targets deep brain regions that are the control centres of several important cognitive functions involved in different neurological and psychiatric pathologies. The research highlights the interdisciplinary approach that integrates medicine, neuroscience, computation, and engineering to improve our understanding of the brain and develop potentially life-changing therapies.

“Invasive deep brain stimulation (DBS) has already successfully been applied to the deeply seated neural control centres to curb addiction and treat Parkinson’s, OCD or depression,” says Hummel. “The key difference with our approach is that it is non-invasive, meaning that we use low-level electrical stimulation on the scalp to target these regions.”

Vassiliadis, lead author of the paper, a medical doctor with a joint PhD, describes tTIS as using two pairs of electrodes attached to the scalp to apply weak electrical fields inside the brain. “Up until now, we couldn’t specifically target these regions with non-invasive techniques, as the low-level electrical fields would stimulate all the regions between the skull and the deeper zones—rendering any treatments ineffective. This approach allows us to selectively stimulate deep brain regions that are important in neuropsychiatric disorders,” he explains.

The innovative technique is based on temporal interference, initially explored in rodent models, and now successfully translated to human applications by the EPFL team. In this experiment, one pair of electrodes is set to a frequency of 2,000 Hz, while another is set to 2,080 Hz. Thanks to detailed computational models of the brain structure, the electrodes are specifically positioned on the scalp to ensure that their signals intersect in the target region.

At this juncture, the magic of interference occurs: the slight frequency disparity of 80 Hz between the two currents becomes the effective stimulation frequency within the target zone. The brilliance of this method lies in its selectivity; the high base frequencies (e.g., 2,000 Hz) do not stimulate neural activity directly, leaving the intervening brain tissue unaffected and focusing the effect solely on the targeted region.

This latest research focuses on the human striatum, a key player in reward and reinforcement mechanisms. “We’re examining how reinforcement learning, essentially how we learn through rewards, can be influenced by targeting specific brain frequencies,” says Vassiliadis. By stimulating the striatum at 80 Hz, the team found they could disrupt its normal functioning, directly affecting the learning process.

The therapeutic potential of their work is immense, particularly for conditions like addiction, apathy and depression, where reward mechanisms play a crucial role. “With addiction, for example, people tend to over-approach rewards. Our method could help reduce this pathological overemphasis,” Vassiliadis, also a researcher at UCLouvain’s Institute of Neuroscience, points out.

Furthermore, the team is exploring how different stimulation patterns can disrupt and potentially enhance brain functions. “This first step was to prove the hypothesis of 80 Hz affecting the striatum, and we did it by disrupting its functioning. Our research also shows promise in improving motor behaviour and increasing striatum activity, particularly in older adults with reduced learning abilities,” Vassiliadis adds.

Hummel, a trained neurologist, sees this technology as the beginning of a new chapter in brain stimulation, offering personalized treatment with less invasive methods. “We’re looking at a non-invasive approach that allows us to experiment and personalize treatment for deep brain stimulation in the early stages,” he says. Another key advantage of tTIS is its minimal side effects. Most study participants reported only mild sensations on the skin, making it a highly tolerable and patient-friendly approach.

Hummel and Vassiliadis are optimistic about the impact of their research. They envision a future where non-invasive neuromodulation therapies could be readily available in hospitals, offering a cost-effective and expansive treatment scope.

How does the brain turn waves of light into experiences of colour?

Color-making in the brain

Researchers have uncovered circuitry in the brains of fruit flies that make colour perception possible for them.  CREDIT Columbia’s Zuckerman Institute

Perceiving something—anything—in your surroundings is to become aware of what your senses are detecting. Today, Columbia University neuroscientists have identified, for the first time, brain-cell circuitry in fruit flies that converts raw sensory signals into colour perceptions that can guide behaviour. 

“Many of us take for granted the rich colours we see daily – the red of a ripe strawberry or the deep brown in a child’s eyes. But those colours do not exist outside of our brains,” said Rudy Behnia, PhD, a principal investigator at Columbia’s Zuckerman Institute and the corresponding author on the paper. Rather, she explained, colours are perceptions the brain constructs as it makes sense of the longer and shorter wavelengths of light detected by the eyes. 

“Turning sensory signals into perceptions about the world is how the brain helps organisms survive and thrive,” Dr. Behnia said. 

“To ask how we perceive the world seems like a simple question, but answering it is a challenge,” added Dr. Behnia “I hope that our efforts to uncover neural principles underlying colour perception will help us better understand how brains extract the features in the environment that are important for making it through each day.” 

In their new paper, the research team reports discovering specific networks of neurons, a type of brain cell, in fruit flies that respond selectively to various hues. Hue denotes the perceived colours associated with specific wavelengths or combinations of light wavelengths, which are not inherently colourful. These hue-selective neurons lie within the optic lobe, the brain area responsible for vision.

Among the hues these neurons respond to are those that people would perceive as violet and others that correspond to ultraviolet wavelengths (not detectable by humans). Detecting UV hues is important for the survival of some creatures, such as bees and perhaps fruit flies; many plants, for example, possess ultraviolet patterns that can help guide insects to pollen. 

Scientists had previously reported finding neurons in animals’ brains that respond selectively to different colours or hues, say, red or green. But no one could trace the neural mechanisms making this hue selectivity possible. 

This is where the recent availability of a fly-brain connectome has proven helpful. This intricate map details how some 130,000 neurons and 50 million synapses in a fruit-fly’s poppy seed-sized brain are interconnected, said Dr. Behnia, who is also an assistant professor of neuroscience at Columbia’s Vagelos College of Physicians and Surgeons.

With the connectome serving as a reference – akin to a picture on a puzzle box serving as a guide for how a thousand pieces fit together – the researchers used their observations of brain cells to develop a diagram they suspected represents the neuronal circuitry behind hue selectivity. The scientists then portrayed these circuits as mathematical models to simulate and probe the circuits’ activities and capabilities. 

“The mathematical models serve as tools that enable us to better understand something as messy and complex as all of these brain cells and their interconnections,” said Matthias Christenson, PhD, a co-first author on the paper and a former member of Dr Behnia’s lab. “With the models, we can work to make sense of all of this complexity.” Also contributing crucially to the modelling work was Dr Larry Abbott, William Bloor, Professor of Theoretical Neuroscience, Professor of Physiology and Cellular Biophysics and a principal investigator at the Zuckerman Institute.

Not only did the modeling reveal that these circuits can host activity required for hue selectivity, it also pointed to a type of cell-to-cell interconnectivity, known as recurrence, without which hue-selectivity cannot happen. In a neural circuitry with recurrence, outputs of the circuit circle back in to become inputs. And that suggested yet another experiment, said Álvaro Sanz-Diez, PhD, a postdoctoral researcher in Dr. Behnia’s lab and the other co-first author of the Nature Neuroscience paper. 

“When we used a genetic technique to disrupt part of this recurrent connectivity in the brains of fruit flies, the neurons that previously showed hue-selective activity lost that property,” said Dr. Sanz-Diez. “This reinforced our confidence that we really had discovered brain circuitry involved in colour perception.”

“Now we know a little more about how the brain’s wiring makes it possible to build a perceptual representation of colour,” said Dr Behnia. “I hope our new findings can help explain how brains produce all kinds of perceptions, including colour, sound and taste.”

Spasticity Treatments Explained by Neurologist

Spasticity Treatments Explained by Neurologist - YouTube

Time stamps:

0:29​ What Causes Spasticity

1:32​ Conservative Treatments

5:13​ Drugs

7:20​ Marijuana

8:43​ Botox

10:49​ Baclofen Pump

12:17​ Other Treatments

Living near major roads linked to risk of dementia, Parkinson’s, Alzheimer’s and MS


Living near major roads or highways is linked to higher incidence of dementia, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis (MS), suggests new research published this week in the journal Environmental Health.

Researchers from the University of British Columbia analyzed data for 678,000 adults in Metro Vancouver. They found that living less than 50 metres from a major road or less than 150 metres from a highway is associated with a higher risk of developing dementia, Parkinson’s, Alzheimer’s and MS–likely due to increased exposure to air pollution.

The researchers also found that living near green spaces, like parks, has protective effects against developing these neurological disorders.

“For the first time, we have confirmed a link between air pollution and traffic proximity with a higher risk of dementia, Parkinson’s, Alzheimer’s and MS at the population level,” says Weiran Yuchi, the study’s lead author and a PhD candidate in the UBC school of population and public health. “The good news is that green spaces appear to have some protective effects in reducing the risk of developing one or more of these disorders. More research is needed, but our findings do suggest that urban planning efforts to increase accessibility to green spaces and to reduce motor vehicle traffic would be beneficial for neurological health.”

Neurological disorders–a term that describes a range of disorders, including Alzheimer’s disease and other dementias, Parkinson’s disease, multiple sclerosis and motor neuron diseases–are increasingly recognized as one of the leading causes of death and disability worldwide. Little is known about the risk factors associated with neurological disorders, the majority of which are incurable and typically worsen over time.

For the study, researchers analyzed data for 678,000 adults between the ages of 45 and 84 who lived in Metro Vancouver from 1994 to 1998 and during a follow-up period from 1999 to 2003. They estimated individual exposures to road proximity, air pollution, noise and greenness at each person’s residence using postal code data. During the follow-up period, the researchers identified 13,170 cases of non-Alzheimer’s dementia, 4,201 cases of Parkinson’s disease, 1,277 cases of Alzheimer’s disease and 658 cases of MS.

For non-Alzheimer’s dementia and Parkinson’s disease specifically, living near major roads or a highway was associated with 14 per cent and seven per cent increased risk of both conditions, respectively. Due to relatively low numbers of Alzheimer’s and MS cases in Metro Vancouver compared to non-Alzheimer’s dementia and Parkinson’s disease, the researchers did not identify associations between air pollution and increased risk of these two disorders. However, they are now analyzing Canada-wide data and are hopeful the larger dataset will provide more information on the effects of air pollution on Alzheimer’s disease and MS.

When the researchers accounted for green space, they found the effect of air pollution on the neurological disorders was mitigated. The researchers suggest that this protective effect could be due to several factors.

“For people who are exposed to a higher level of green space, they are more likely to be physically active and may also have more social interactions,” said Michael Brauer, the study’s senior author and professor in the UBC school of population and public health. “There may even be benefits from just the visual aspects of vegetation.”

Brauer added that the findings underscore the importance for city planners to ensure they incorporate greenery and parks when planning and developing residential neighbourhoods.

Multiple system atrophy – so what is Multiple system atrophy? Please don’t ignore as this is important!




Multiple system atrophy

Multiple system atrophy




Multiple system atrophy is a rare nervous system disorder where nerve cells in several parts of the brain deteriorate over time.

This causes problems with balance, movement and the autonomic nervous system, which controls a number of the body’s automatic functions, such as breathing and bladder control.

 

Symptoms of multiple system atrophy

Symptoms of multiple system atrophy usually start when someone is between 50 and 60 years of age, but they can come at any time after 30.

The symptoms are wide-ranging and include muscle control problems, similar to those of Parkinson’s disease.

Many different functions of the body can be affected, including the urinary system, blood pressure control and muscle movement.

Although there are many different possible symptoms of multiple system atrophy, not everyone who’s affected will have all of them.

Bladder problems

Men and women with multiple system atrophy will usually have one or more of the following bladder symptoms:

constantly feeling the need to pee

peeing more frequently

loss of bladder control

being unable to empty the bladder properly

being unable to pee




Erection problems

Men with multiple system atrophy will usually experience erectile dysfunction (the inability to get and maintain an erection), although this is a common problem that many men without the condition develop.

Low blood pressure when standing up

Someone with multiple system atrophy will often feel lightheaded, dizzy and faint after standing up. This is known as postural hypotension and is caused by a drop in blood pressure when they stand upright.

When you stand up after lying down, your blood vessels usually narrow quickly and your heart rate increases slightly to prevent your blood pressure from dropping and decreasing blood flow to your brain.

This function is carried out automatically by the autonomic nervous system; however, this system doesn’t work properly in people with multiple system atrophy, so the control is lost.

Problems with co-ordination, balance and speech

In multiple system atrophy, a part of the brain called the cerebellum is damaged. This can make the person clumsy and unsteady when walking, and can also cause slurred speech.

These problems are collectively known as cerebellar ataxia.

Slowness of movement and feeling stiff

A person with multiple system atrophy has much slower movements than normal (bradykinesia). This can make it difficult to carry out everyday tasks. Movement is hard to initiate, and the person will often have a distinctive slow, shuffling walk with very small steps.

Some people may also have stiff, tense muscles. This can make it even more difficult to move around and cause painful muscle cramps (dystonia).

The above symptoms are typical of Parkinson’s disease but, unfortunately, the medication used to relieve them in people with Parkinson’s disease (levodopa) isn’t very effective for people with multiple system atrophy.

Other signs and symptoms

People with multiple system atrophy may also have:

shoulder pain and neck pain

constipation

cold hands and feet

problems controlling sweating

muscle weakness in the body and limbs – it may be more pronounced in one arm or leg

uncontrollable laughing or crying

sleep problems – insomniasnoringrestless legs or nightmares

noisy breathing and unintentional sighing

a weak, quiet voice

swallowing problems

blurred vision

depression

dementia (although this is uncommon)

Causes of multiple system atrophy

The causes of multiple system atrophy aren’t well understood.

It doesn’t appear to be inherited – there’s no evidence that an affected person’s children will develop it.

However, it’s possible that both genetic and environmental factors may contribute, so research is currently looking at whether there’s a genetic tendency (predisposition) to develop it.

The brain cells of a person with multiple system atrophy contain a protein called alpha-synuclein. A build-up of abnormal alpha-synuclein is thought to be responsible for damaging areas of the brain that control balance, movement and the body’s autonomic functions.

Diagnosing multiple system atrophy

There’s no specific test to diagnose multiple system atrophy.

A diagnosis can usually be made based on the symptoms, although it can potentially be confused with Parkinson’s disease.

Multiple system atrophy or Parkinson’s disease?

A person is more likely to have multiple system atrophy rather than Parkinson’s disease if:

their symptoms have progressed rapidly  a person with Parkinson’s disease deteriorates more slowly

they’ve experienced falls in the early stages of the condition – this isn’t a typical symptom of Parkinson’s

they don’t respond well to levodopa therapy  levodopa can significantly improve symptoms of Parkinson’s disease

their speech is severely affected  this isn’t a typical symptom of Parkinson’s disease

they gasp and breathe noisily  this isn’t a typical symptom of Parkinson’s disease

Further tests

If multiple system atrophy is suspected, a doctor (usually a neurologist) will test the person’s reflexes and “automatic” bodily functions, such as their bladder function.

A brain scan is often needed – usually an MRI scan or a SPECT scan – to detect any loss of brain cells. Read more about SPECT scans (PDF, 304kb).

More detailed assessments of autonomic function may also be carried out – for example, recording blood pressure changes when lying down and standing.

Treating multiple system atrophy

There’s currently no cure for multiple system atrophy and no way of slowing its progression.

People with the condition typically live for six to nine years after their symptoms start and may deteriorate quickly during this time. Some people may live for more than 10 years after being diagnosed.

Help and support is available, and the symptoms can be managed so that the person is as independent and comfortable as possible.

Read about the:

treatment of low blood pressure

treatment of constipation

treatment of urinary incontinence

treatment of swallowing problems

Physiotherapy and occupational therapy can help people with multiple system atrophy stay mobile and maintain fitness and muscle strength.

Help and support

Help for carers

Practical and financial help is available if you care for someone with multiple system atrophy.

Your local authority can carry out a carers’ assessment to assess your needs and determine the help and support you’re entitled to.

Find out more about carers’ assessments.

Support for people with multiple system atrophy

If you have multiple system atrophy and are finding coping with day-to-day life difficult, your doctor or nurse can refer you to a social worker.

They can carry out an assessment and recommend the help you require. For example, you may need:

care attendants – who can help with everyday tasks such as housework, dressing and washing

meals on wheels  your local council may be able to offer financial help for this; check your eligibility for getting meals at home

benefits – you may be eligible for a number of benefits, such as Attendance Allowance and Personal Independence Payment (PIP)

home adaptations – to make moving around at home easier and ensure your home environment is as comfortable as possible

Find out more about care and support needs assessments.