Exploring Deep Brain Stimulation for Clinical Depression

1. Bionics 5 Kevin Warwick

2. Deep Brain Stimulation • It is a surgical treatment involving the implantation of electrodes, which send electrical impulses to the specific parts of the brain in which they have been positioned by the surgeon. • First ‘official’ treatments like this were commenced in 1997. • Most common use is to arrest the tremor associated with Parkinson’s Disease – we will deal with this in a separate lecture. • Also found to be useful for depression. • Can be side effects!!

3. Deep Brain Stimulation • Definitely this is “Bionic”, as ultimately the person’s brain is operating partly due to its biological function and partly in response to electronic stimulation. • We will look here at what DBS is. • We will look at the sort of cases that DBS is presently employed to tackle.

4. Operation • Only dealing with serious/long term cases here – where all else has failed. • Surgery can last for 10+ hours • Test signals input during operation

5. Components • The system consists of three elements: • The implanted pulse generator (IPG): is a battery powered neurostimulator encased in a titanium housing, which sends electrical pulses to the brain to modify the neural activity at the target site. • The electrode lead: is a wire insulated in polyurethane with four/six platinum iridium electrodes at its tip and is usually placed in one of three areas of the brain. • An extension wire: connects the lead to the IPG. It is an insulated wire that runs from the head, down the side of the neck, behind the ear to the IPG, which is placed subcutaneously. • The IPG is adjusted and calibrated by a neurologist/surgeon to optimize symptom suppression and control side effects.

6. Surgery • The procedure begins with preoperative identification of the neurosurgical target using Computed Tomography (CT) or MRI. • During surgery, the patient is given local anaesthesia and remains awake. A craniotomy is performed and a DBS lead is placed either unilaterally or bilaterally, depending on the patient's symptoms. • Microelectrode recording may be used to more precisely locate the desired target within the brain. • The IPG and extension are subsequently implanted and connected to each lead.

7. Uses of DBS • Main use is for PD • Potential use with Epilepsy?? • Clinical Depression • Tourette Syndrome • Obsessive-Compulsive Disorder • Severe Persistent Pain – such as Phantom Limb pain

8. Clinical Depression • It is a state of intense sadness or despair that is disruptive to a person’s social functioning and life. • Term ‘depression’ is used widely to describe (in everyday terms) a low mood – doesn’t affect main functioning. • Clinical depression is a clinical diagnosis, i.e. someone else (a doctor) agrees with you that you are depressed. • Clinically depressed - feeling sad for no reason or having no motivation to do anything. • Person may feel tired, sad, irritable, lazy, unmotivated, and apathetic. • It leads to constant negative thinking and sometimes abuse (alcohol/drugs) or self-harm. Extreme depression can culminate in its sufferers attempting or committing suicide.

9. Clinical Depression • Treatment by Electric Shock? • Electroconvulsive therapy (ECT) uses short bursts of a controlled electric current (typically 0.9 Amps) passed into the brain to induce a brief seizure while the patient is under anaesthesia. • Typically a patient receives three treatments per week over three or four weeks. Repeat sessions may be needed. Memory loss, disorientation, and headache are very common side effects. • ECT offers the benefit of a very fast response; however, this response has been shown not to last unless maintenance electric shock or maintenance medication is used. • Antidepressants usually take around a month to take effect, whereas the results of ECT have been shown to be much faster. It is the treatment of choice in emergencies (e.g., when the patient has ceased oral intake of fluid or nutrients). • There remains much controversy over electric shock treatment!

10. Clinical Depression • DBS is still an experimental method of dealing with clinical depression. • Tested only in extreme cases thus far – where drugs, ECT etc have failed • Electrode target – Brain Area 25 – frontal cortex. • When electrodes are switched on, patients describe a ‘black cloud lifting’ – immediately more interested in life. • When electrodes are switched off – depression returns. • Alternative area for stimulation – nucleus accumbens – associated with pleasure/reward – similar results.

11. Tourette Syndrome • It is an inherited neurological disorder with typical onset in childhood. • It is characterized by the presence of multiple physical (motor) tics and vocal (phonic) tics. • These tics characteristically wax and wane. • People with Tourette's have normal life expectancy and intelligence. Can reduce in teens. • Tourette's was once regarded as rare and bizarre, most often associated with the exclamation of obscene words – actually only a very small proportion – also echoing & repeating.

12. Tourette Syndrome • Treatment for mild cases – simply managing them – psycho behavioural therapy, education, and reassurance. • No cure – different drugs help with different types of the syndrome. • 20% of persons with Tourette syndrome do not recognize that they have tics. • Treatment problems due to intermittent behaviour and lack of knowledge as to what stimuli start them at a particular time.

13. Tourette Syndrome • DBS has been used experimentally/successfully in a few patients with severe cases. • Study is needed to determine whether long term benefits outweigh the risk. • Complications include "short battery life, abrupt symptom worsening upon cessation of stimulation and significant time and effort involved in optimizing stimulation. • All cases experienced reduction in tics. • Lots of questions: There may be serious short- and long-term risks. Expert care &support required. Difficult to assess exact electrode positioning. • Not so suitable for children – as it may go away.

14. Obsessive-Compulsive Disorder • It is an anxiety disorder characterized by a subject's obsessive thoughts and related compulsions (fituals) which attempt to neutralize the obsessions. • It is listed by the WHO as one of the top 10 most disabling illnesses in terms diminished quality of life. • A person who shows signs of infatuation or fixation with a subject/object, or displays traits such as perfectionism, does not necessarily have OCD, a specific and well-defined condition.

15. Obsessions • Recurrent and persistent thoughts or impulses that are experienced as intrusive and that cause distress. • The person can attempt to ignore or suppress such thoughts or impulses or to neutralize them with some other thought or action. • It is important for the person to recognize that the obsessional thoughts or impulses are a product of his or her own mind, and are not based in reality. • The tendency is to haggle over small details that the person is unable to permanently fix or change in any way. This begins a mental pre-occupation with that which is inevitable.

16. Compulsions • Compulsions are repetitive behaviours that the person simply must perform in response to an obsession - according to rules that must be applied rigidly. • These behaviours are supposedly aimed at preventing or reducing distress or preventing some terrible event or situation, • The behaviours are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive. • In addition, at some point, the sufferer must realize that his/her obsessions or compulsions are unreasonable or excessive. Moreover, the obsessions or compulsions can be time-consuming, can cause distress, or cause impairment in social functioning.

17. OCD – Examples 1 • Repeated hand washing. • Repeated clearing of the throat, although nothing may need to be cleared. • Arranging objects in groups of three, grouping objects in odd numbered groups. • Counting steps, e.g. the need to take 12 steps to the car in the morning. • Aligning objects at absolute right angles or perfectly parallel. • Having to "cancel out" bad thoughts with good thoughts, e.g. Imagining harming a child and having to imagine a child playing happily.

18. OCD – Examples 2 • Sexual Obsessions or unwanted sexual thoughts. • Fear of contamination; fearing the presence of human body secretions such as sweat or vomit or excretions such as urine or feces. Fear that the soap they're using is contaminated. • A need for both sides of the body to feel even. If one hand gets wet, the sufferer may feel very uncomfortable if the other is not. If the sufferer is walking and bumps into something, he/she may hit the object or person back to feel a sense of evenness. Conversely some sufferers would rather things to be uneven. • An obsession with numbers.Some people are obsessed with even numbers, loathing odd numbers (causes anxiety and can make the person very angry). • Twisting the head on a toy around, then twisting it all the way back.

19. DBS Treatment for OCD • Tested and successful on extreme cases only – where all else has failed. • Procedure still questioned for this sort of use. • Little known as to what actual effects the DBS is having in the brain. • No long terms results yet. • Side-effects still a research question.

20. Persistent pain • Pain is categorized in a number of ways – we are only interested here in extreme cases – where DBS could be used. • Phantom Limb pain • Neuropathic pain • Visceral (organ) pain • Not so interested (yet) in somatic or cutaneous pain

21. Visceral Pain • Originates from body's viscera (organs). • Nociceptors are located within body organs and internal cavities. • The scarcity of nociceptors in these areas produces a pain that is aching and of a longer duration than somatic pain. • Visceral pain is difficult to localize, and injuries to visceral tissue can exhibit referred pain, where the sensation is localized to an area unrelated to the site of injury. • Myocardial ischaemia (loss of blood flow to part of the heart muscle) is a good example. The sensation can occur as an ache in the left shoulder or hand. • Referred pain can be explained by the findings that pain receptors in the viscera also excite spinal cord neurons that are excited by cutaneous tissue. Since the brain normally associates firing of these spinal cord neurons with stimulation of somatic tissues in skin or muscle, pain signals arising from the viscera are interpreted by the brain as originating from the skin.

22. Phantom Limb Pain • It is the sensation that an amputated or missing limb is still attached to the body and is moving along with other body parts. • 70% of amputees experience phantom sensations, the majority report that the sensations are painful. • Phantom sensations, a referred pain, may also occur after the removal of body parts other than the limbs, e.g. after amputation of the breast, extraction of a tooth (phantom tooth pain) or removal of an eye. • Phantom pains can occur in people who are paralysed or born without limbs. • Sensations can include warmth, cold, itching, squeezing and burning. • The missing limb often feels shorter and may feel as if it is in a distorted and painful position. Occasionally, the pain can be made worse by stress or weather changes.

23. Phantom Limb Pain • The dominant theory for cause of phantom limbs used to be - irritation in the severed nerve endings. When a limb is amputated, severed nerve endings are terminated at the remaining stump. These nerve endings can become inflamed, and may send anomalous signals to the brain. These signals, being functionally nonsense, were thought to be interpreted by the brain as pain. • Treatments based on this theory were failures. Sometimes surgeons would perform a second amputation, shortening the stump, hoping to remove the inflamed nerve endings and cause temporary relief. Instead, the phantom pains increased, and many were left with the sensation of both the original phantom limb, as well as a new phantom stump, with a pain all its own. • In some cases, surgeons cut the sensory nerves leading into the spinal cord or in extreme cases removed the part of the thalamus that receives sensory signals from the body.

24. Neuropathic Pain • Disease of the peripheral nerves • Often results in numbness and neuralgia – very different from pain due to stubbing a toe. • Neuropathic pain is usually perceived as a steady burning or like an electric shock. The difference is due to the fact that "ordinary" pain stimulates only pain nerves, while a neuropathy often results in the firing of both pain and non-pain (touch, warm, cool) sensory nerves in the same area, producing signals that the spinal cord and brain do not normally expect to receive. • Only very extreme cases can be considered for DBS • Acts as a pain blocker

25. Problems/Side Effects? • When using DBS to tackle a problem, various side-effects have been reported. • Examples: hallucinations, hyper sexuality, compulsive gambling, depression, cognitive dysfunction and apathy. • Extreme/few cases: voyeurism & suicide. • Could be due to shifting electrodes or bleeding • Possibly reversible conditions (not-suicide!) • Small %age of the total + compare with original problem • May even have occurred anyway.

26. Comments • DBS still in its infancy • Presently only employed in more extreme cases • Very experimental – handful of surgeons • Potentially could be used for many other problems, e.g. arthritis. • Electrode position, signal frequency and magnitude are to be investigated

27. Next Lecture • Human Enhancement