St Patrick's Science! Deep Brain Stimulation

Today was a raw, rainy day, not exactly the day for a parade and other festivities.  Besides, my department is down to two persons on active status... luckily, my friend Jim is recovering from surgery, though in his inimitable fashion, he noted 'they cracked me open like an oyster'.  Suffice it to say, I am at work, and in a quiet moment, I will be listening to tonight's Secret Science Club lecture featuring psychiatrist and biomedical engineer Dr Alik Widge.  Dr Widge is affiliated with the University of Minnesota, and tonight's lecture is the annual Dana Foundation neuroscience lecture.

Dr Widge began his lecture, titled Brain Stimulation, Brain Circuits, and Mental Health with an invitation to an overview of what goes on electrically in the brain, and how the brain 

Brain is an information processing engine- brain problems are disruptions in circuits and need circuit-oriented treatment... specific communication pathways in the brain.  Circuit oriented treatment, nudging the brain's circuitry, is promising, but is expensive and difficult to do.  

Mental illness is a public health crisis.  $201 billion/year healthcare spending and up to ten times that in lost productivity.  Mental illnesses, typically beginning in one's teens or twenties, kill slowly.  They can often be treated through medications or talk therapy, but often cannot be cured.  Even patients who are successfully treated can have relapses.  There are long periods of trial and error in medicating patients, which is discouraging to patients.  These treatments aren't focal, they flood the brain with an neurotransmitter in the hope of fixing a problem.  Mental disorders are network disorders, they aren't simply chemical.  One of the streets in the brain has potholes or other traffic problems- the illnesses are hard to see because they result from subtle problems in the brain's pathways.

Electrical solutions to brain problems have been around for about a half century- in particular, electroconvulsive therapy, a controlled seizure under anaesthesia (Dr Widge noted that it's way more boring than what is seen in movies).  It is hard to scale up, requiring anesthesia and multiple MDs, but it works on about two-thirds of patients.

Transcranial Magnetic Stimulation is much easier, requireing no anesthesia, and few side effects.  It uses strong magnetic fields to manipulate electrical activity in highly targeted areas of the brain.  It works for treatment-resistant depression in about two-thirds of patients.  It is not useful for other mental illnesses, and it does involve regular office visits, making it difficult for individuals not residing in large cities.  Also, patients tend to relapse in a year, requiring additional treatment.

An invasive approach is Deep Brain Stimulation, involving a pencil graphite sized wire implanted in the brain and attached to a pacemaker-type electrical system in the chest.  It was first used for Parkinson's and other tremor disorders.  The deeper one goes in the brain, the 'older' the brain is- evolution added layers to the brain, culminating in the cerebral cortex which makes us human.  

Deep brain stimulation was used in patients that other therapies could not treat- Dr Widge noted that the word 'miracle' was thrown around a lot.  It's rollout coincided with his graduation from medical school.  He noted that random trials were conducted with all subjects getting implants, but only half of the implants were activated.  The placebo was inactive, but the examiners would pretend to turn on the systems.  Eventually, all of the systems were activated, but the action can be manipulated in various ways- Dr Widge noted that this is a blessing and a curse... they are customizable, but the proper treatment is largely trial-and-error.  If a patient is lucky, the treatment is immediately successful, but if a patient is unlucky, it can take time for a doctor to 'dial in' a proper treatment.  Sometimes, a successfully treated patient will have the system turned off, and will relapse, necessitating a reboot.  This is also a test of instances in which the batteries run out.

These invasive treatments are expensive and it's hard to predict in advance who will benefit (proper fine-tuning is needed).  When people get better, the results are dramatic even in patients who do not respond to less invasive treatments.

There is a need for getting more specific, targeting cognitive flexibility... Dr Widge told us to think beyond 'depression', the term really doesn't work.  There are 500 symptom clusters which can result in a diagnosis of depression... what if someone from the wrong subset of patients is chosen for invasive procedures?  How can we tell if a patient's primary problem is depression or generalized anxiety disorder, PTSD, or something from the addiction cluster?  

Why can't we tell these disorders apart?  They have overlapping symptoms.  There is a need to go deeper, to ask questions about symptoms- is a patient afraid, impulsive, taciturn, labile?  Is a patient stuck?  For every depression study, there is an OCD study, which had similar results from deep brain stimulation... the diagnoses are not considered related, but they are regulated by similar locations in the brain.  People with OCD and depression get 'stuck'- an OCD patient is temporarily stuck until a ritual is performed, while people with depression get stuck in long-term low points.  Does deep brain stimulation target one's cognitive flexibility?  Does it 'unstick' the brain, resulting in more flexible thought processes?  It's usually a 5%, maybe 10% improvement in decision-making speed, resulting in a subtle behavioral effect.  

Can the responses be quickly measured in order to do some fast auto-tuning?  Experiments were not conducted on psychiatric patients, but epilepsy patients with temporary electrodes in the brain implanted in areas close to sites used in deep-brain stimulation.  Auto-triggered simulation, a closed loop therapy applied when the brain needed a boost, as way more effective than non-oriented stimulation.  

Can patients be 'nudged' towards healthier, disease-fighting behaviors?  These treatments wouldn't directly cure mental illnesses, but they could initiate and self-help, leading to recovery- not just for depression, but OCD, PTSD, and addiction.  This would be a new rehabilitative/assisting model of mental health treatment.  The difficulty is getting this model out of the lab and into the real world- the equipment is expensive.

If we can understand the difficulties in connections in the brain, we could determine how to improve flexibility.  Dr Widge compared the firing of brain cells to a radio wave or heartbeat- there are rhythmic waves which can synch up, becoming coherent.  These electrical rhythms, synced up between areas, act as carrier frequencies to help information transmission.

In epilepsy patients, numerous electrodes are implanted in the brain in order to locate the area of the brain in which the seizures originate (typically in order to excise that portion of the brain).  Because these patients are bedridden while this detection occurs, they are often asked to perform tasks so neurologists can measure other brain functions- these tasks help to alleviate boredom.  In measuring brain engagement, multiple brain connections contribute information, allowing 'wiring diagrams' to be made to determine how to used targeting stimulation to increase flexibility.

By listening to one brain region, and using a single electrical pulse to nudge another brain region, brain areas which don't 'want' to sync up can be forced to synchronize.  Similarly, communication between brain regions can be decreased.  Eventually, the goal is to shrink down the equipment to something which can be powered by a cell phone battery.

We are on the cusp of changing the way that mental illness is treated, using electrical nudging when it is needed.  We need to start talking less of depression and more about brain flexibility issues, network problems.  Cognitive inflexibility is a low-hanging fruit, other mental health problems are more complicated- the toolkit needs to be expanded, doctors need to speak 'engineer', and equity must be achieved... black, brown, and poor persons have less access to clinical health trials and expensive treatments.  The taxpayers who fund these studies must benefit from them.

The lecture was followed by a Q&A session.  How do researchers know that brain problems are electric?  Patterns of electrical activity have been measured among a wide array of animal subjects.  Physical changes in the brain lead to electrical changes- the brain is an electrical organ.  

Are there activities which can improve brain flexibility?  There is no set procedure, Dr Widge suggested doing something new on a regular basis- give the brain novelty, that's your best bet.  

Another question involved treatment of obesity- the issue is that it is unknown whether obesity involves an addiction or not.  Eating disorders such as anorexia nervosa are better known- they tend to be related to OCD, and involve getting stuck into thought patterns.  Obesity is much more of a multi-factorial issue.

Asked about borderline personality disorders, Dr Widge noted that treating them was a major inspiration, he is working to set patients free from the parts of their brains that are preventing them from doing what they want to do.

Can patients get habituated to deep brain stimulation?  Absolutely, sometimes the electricity must be turned up.  By only activating the stimulation when needed, it is hoped that this habituation can be prevented.

Regarding autism, this work has not been tried.  Given connections between autism and OCD, there might be success in using DBS.  Most of the work is done in clinical depression, though, because that is where the money is.  To expand these studies, major medical device manufacturers need to get involved, and they want to treat the largest amounts of patients.  Once depression is tackled, other diseases can be knocked down one-by-one.

Individuals with depression have electrical 'wiring' problems, and these problems often result from trauma- environmental, familial, and other factors play a role in damaging the 'circuitry'.  A lot of times, people can develop the flexibility to make changes to their lifestyles, such as moving out of unhappy homes or seeking employment.  When Dr Widge has his 'doctor hat' on, he takes a holistic approach, despite specifically talking about DBS technology tonight.

Regarding the need for invasive implants, Dr Widge noted that most medicines start out with intravenous injections, then oral versions are eventually developed.  The physicists are at work as well as the neuroscientists, so less invasive devices may be around in his lifetime, if not the next five years.

There is a danger to self-administration of DBS- one side effect is euphoria, which can lead to behavioral problems.  In the case of people who are feeling 'too good', and engage in problematic activity, the stimulation needs to be toned down.  Total control over one's brain is dangerous, just as totally accessible machinery would pose risks to untrained persons.  Future doctors will have to engage in shared decision making with patients, weighing their needs and wants.

Are there ethical implications to having access to a chip in the brain?  Dr Widge joked, "Trust me, I'm a doctor."  He noted that there are ethical studies regarding this research.  He also noted that mind control is not possible.  He might be able to nudge a patient about 5%, but couldn't make them walk through the door.  Ethicists are on-hand to conduct interviews with patients, and most of them articulate that the therapy allows them to be their true selves.  The same ethical fears were applied to medications like Prozac.  Dr Widge then held up his empty glass and noted that his alcoholic beverage involved an ethical choice, and consuming it posed ethical issues, such as the ethics of driving.

Are there off-target effects to Deep Brain Stimulation and Cognitive Flexibility Therapy?  There's no such thing as a free lunch, but any side effects are unknown at this time.  Could there be deleterious effects, such as temporary deficits in mathematical skill or changes in impulsivity, that need to be quantified?  Stay tuned!

Regarding DIY TDCS, it's a Wild West situation akin to getting meds on a website.  It's not voodoo, but it's not well-studied.  Use with caution! 

Dr Widge ended the session by noting that he was taking baby steps.  He joked that he's involved in a mission to the Moon, but the questions he's receiving concern interstellar missions.  He needs to integrate his work with the work of others, using multi-pronged approaches.

Once again, my great and good friends of the Secret Science Club, in conjunction with the good people of the Dana Foundation, have served up a fantastic lecture.  Kudos to Dr Widge, Dorian and Margaret, and the folks at Dana.  For a taste of that SSC experience, here is a video of Dr Widge discussing brain network stimulation:

 

Pour yourself a nice beverage and soak in that SCIENCE!