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Deep brain stimulation: a fix when the drugs don’t work

Neurological disorders can have a devastating impact on the lives of sufferers and their families. Symptoms of these disorders differ extensively - from motor dysfunction in Parkinson’s disease, memory…

Implanted electrodes can alleviate symptoms of Parkinson’s and Alzheimer’s, and help treat addiction. Wikimedia Commons

Neurological disorders can have a devastating impact on the lives of sufferers and their families.

Symptoms of these disorders differ extensively - from motor dysfunction in Parkinson’s disease, memory loss in Alzheimer’s disease to inescapable cravings in drug addiction.

Drug treatments are often ineffective in these disorders. But what if there was a way to simply switch off a devastating tremor, or boost a fading memory?

Recent advances using Deep Brain Stimulation (DBS) in selective brain regions have provided therapeutic benefits and have allowed those affected by these neurological disorders freedom from their symptoms, in absence of an existing cure.

A pacemaker for the brain

Artificial cardiac pacemakers are typically associated with controlling and resynchronising heartbeats by electrical stimulation of the heart muscle.

Schematic of deep brain stimulation. stutteringmedia

In a similar manner, DBS sends electrical impulses to specific parts of the brain that control discrete functions. This stimulation evokes control over the neural activity within these regions.

Prior to switching on the electrical stimulation, electrodes are surgically implanted within precise brain regions to control a specific function.

The neurosurgery is conducted under local anaesthetic to maintain consciousness in the patient. This ensures that the electrode does not damage critical brain regions.

The brain itself has no pain receptors so does not require anaesthetic.

Following recovery from surgery the electrodes are activated and the current calibrated by a neurologist to determine the optimal stimulation parameters.

The patient can then control whether the electrodes are on or off by a remote battery-powered device.

Deep Brain Stimulation surgery.

Turning off tremors

Perhaps the most documented success of DBS is in the control of tremors and motor coordination in Parkinson’s disease.

This is caused by the degeneration of neurons in an area of the brain called the substantia nigra. These neurons secrete the neurotransmitter dopamine.

Basal ganglia circuits, including substantia nigra. Wikimedia Commons

Deterioration of these neurons reduces the amount of dopamine available to be released in a brain area involved in movement, the basal ganglia.

Drug therapy for Parkinson’s disease involves the use of levodopa (L-DOPA), a form of dopamine that can cross the blood brain barrier and then be synthesised into dopamine.

The administration of L-DOPA temporarily reduces the motor symptoms by increasing dopamine concentrations in the brain. However, side effects of this treatment include nausea and disordered movement.

DBS has been shown to provide relief from the motoric symptoms of Parkinson’s disease and essential tremors.

For the treatment of Parkinson’s disease electrodes are implanted into regions of the basal ganglia - the subthalamic nucleus or globus pallidus, to restore control of movement.

These are regions innervated by the deteriorating substantia nigra, therefore the DBS boosts stimulation to these areas.

Patients can then switch on the electrodes, stimulating these brain regions to enhance control of movement and diminish tremors.

Restoring fading memories

Recently, DBS has been used to diminish memory deficits associated with Alzheimer’s disease, a progressive and terminal form of dementia.

British author Terry Pratchett has been diagnosed with Alzheimer’s Disease. Bolt of Blue

The pathologies associated with Alzheimer’s disease involve the formation of amyloid plaques and neurofibrillary tangles within the brain leading to dysfunction and death of neurons.

Brain regions primarily affected include the temporal lobes, containing important memory structures including the hippocampus.

Recent clinical trials with DBS involve the implantation of electrodes within the fornix – a structure connecting the left and right hippocampi together.

By stimulating neural activity within the hippocampi via the fornix, memory deficits associated with Alzheimer’s disease can be improved, enhancing the daily functioning of patients and slowing the progression of cognitive decline.

Deactivating addiction

Another use of DBS is in the treatment of substance abuse and drug addiction. Substance-related addictions constitute the most frequently occurring psychiatric disease category and patients are prone to relapse following rehabilitative treatment.

Persistent drug use leads to long term changes in the brain’s reward system.

Understanding of the reward systems affected in addiction has created a range of treatment options that directly target dysregulated brain circuits in order to normalise functionality.

One of the key reward regions in the brain is the nucleus accumbens and this has been used as a DBS target to control addiction.

Translational animal research has indicated that stimulation of the nucleus accumbens decreases drug seeking in models of addiction. Clinical studies have shown improved abstinence in both heroin addicts and alcoholics.

Diagram of a rat self-administering morphine. Wikimedia Commons

Studies have extended the use of DBS to potentially restore control of maladaptive eating behaviours such as compulsive binge eating.

In a recent study, binge eating of a high fat food in mice was decreased by DBS of the nucleus accumbens. This is the first study demonstrating that DBS can control maladaptive eating behaviours and may be a potential therapeutic tool in obesity.

Despite its therapeutic use for more than a decade, the neural mechanism of DBS is still not yet fully understood.

The remedial effect is proposed to involve modulation of the dopamine system – and this seems particularly relevant in the context of Parkinson’s disease and addiction.

DBS potentially has effects on the functional activity of other interconnected brain systems. While it can provide therapeutic relief from symptoms of neurological diseases, it does not treat the underlying pathology.

But it provides both effective and rapid intervention from the effects of debilitating illnesses, restoring activity in deteriorating brain regions and aids understanding of the brain circuits involved in these disorders.

Join the conversation

9 Comments sorted by

  1. Charles Watson

    John Curtin Distinguished Professor of Health Science at Curtin University

    This is a nice summary of the use of DBS, but it is badly out of date. I am not a neurosurgeon but my reading tells me that the globus pallidus and sub thalamic nucleus are no longer the prime targets in Parkinsons' disease. It was found about six years ago that the caudal zona incerta was a much better site for stimulation than the subthalamic nucleus. More recently, it has been found that the peduculopontine segmental nucleus in the isthmus is also a good target, and stimulation there can be combined with stimulation in the caudal zona incerta.

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    1. John Newton

      Author Journalist

      In reply to Charles Watson

      Charles I saw no mention there of motor neurone- does such stimulation work in that case?

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    2. Charles Watson

      John Curtin Distinguished Professor of Health Science at Curtin University

      In reply to John Newton

      I guess you mean motor neuron disease John. The main problem in MND is that the motor neurons progressively die, whereas in Parkinson's disease the problem is with high level control systems. The function of these control systems can be altered with drugs and deep brain stimulation. In MND the situation is a bit like failure of one or more of the engines in a 747 - no amount of fiddling with the electronic control systems in the cockpit will help the fact that the engine has stopped working.
      I should say that there are also some central control problems in MND but they are not the main problem, and we do not understand them well.

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  2. Terry J Wall
    Terry J Wall is a Friend of The Conversation.

    Still Learning at University of Life

    I have a few problems with this type of reactionary high cost treatment:

    First it is only a treatment and an expensive one at that. I would be much more interest if the article was analyzing life style choices, family history, dietary choices. This would empower the population, by allowing them to make choices to AVOID the disease(s).

    Secondly, I cannot see how this sort of approach is going to make medicine affordable and sustainable and as a result, improve the Gross Domestic Happiness factor.

    But now I really think about it, the whole idea would be silly. Less money for Doctors, pharmaceutical companies and makers of medical equipment. No that wouldn't have any wheels under it at all.

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    1. Charles Watson

      John Curtin Distinguished Professor of Health Science at Curtin University

      In reply to Terry J Wall

      there is quite a lot of truth in what you say Terry. However in the case of Parkinson's disease we do not know anything about how to prevent it. Of course, the view on whether money should be spent on management of diseases like Parkinson's changes a lot if you have the disease yourself, or if a family member has it! My betting is that if you had signs of Parkinson's disease you would look for treatment options.

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    2. Michaela Patel

      Primary & Secondary Teacher

      In reply to Terry J Wall

      It's all very well to talk of avoiding or preventing disease - personally, I think that's the way to go in terms of reducing the health costs of lifestyle diseases. The problem is for diseases whose causes we don't know. Parkinsons, MND, Alzheimers still have no confirmed causes or triggers.

      In things like Parkinsons, particularly early onset Parkinsons, which can start in your 30s (like Michael J Fox), good treatment can mean the difference between working until normal retirement age (possibly) or taking a very early retirement and then being supported by the taxpayer for the rest of your life (since you won't have built up your super savings through work!).

      Treatment like DBS is expensive, but it can recoup a lot of money in terms of keeping people functioning, working, and paying taxes for a lot longer. It can potentially reduce the amount of pharmaceuticals used too, as DBS is a non-drug treatment.

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    3. Kaye Hargreaves

      Retired

      In reply to Terry J Wall

      I commend the people who have replied with restraint. I'm struggling to follow their example. You are being very moralistic e and judgemental. On what basis do you imply that people don't deserve medical treatment? That their illness is self-inflicted? Hardly the case with Parkinson's, MND or Alzheimer's. Maybe your reaction was triggered by the mention of drug addiction and binge eating. But isn't there evidence that these behaviours and the associated health problems are themselves caused in part…

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    4. Terry J Wall
      Terry J Wall is a Friend of The Conversation.

      Still Learning at University of Life

      In reply to Kaye Hargreaves

      Hi Kaye

      How do you make a mouse obese? Would you not add "Feed them with highly process trans-fat saturated junk food, with a little soda pop sweetened with broken sweeteners?" Or would that be too silly? I am sure, judging by the people / shopping trolleys I see that these foods make you obese real fast or if that is still too much, can I suggest you watch three DVDs titled Food Matters and Food Inc and Super Size Me.

      Health does not have to come out of a laboratory - but disease diagnosis and treatment does.

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  3. Fred Moore

    Builder

    Bad Beds and worse Dentists:

    Disease in the brain is related to vascular Dgen and to neural pathway ingress of bacteria from rotten teeth.

    With dentistry a hi-tech, double Porche driving, rich man's black-art and beds all based on a 9x7 4inch spine & artery torturing, steel coil design, I am frankly AMAZED that there are so few cases of brain disease.

    I know the solution to this problem but even if I tell you No government will interfere with the big money making Dentistry & Bed manufacturing…

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