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 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.
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.
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.
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.
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.
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.
The terracotta Royals, Kalna, India
Kalna is a small town in the district of Burdwan, West Bengal, India, about 82 km from Kolkata (Calcutta ). It boasts of several magnificent temples ornamented with finest terracotta arts.
Pratapeswar temple is a fine example of 19th century terracotta temple of Bengal. Technically, it is of REKH-DEUL architecture with a curvilinear spire & a single arched entrance. It is decorated with terracotta art of the finest kind.
A primer on ocean acidification. What it is. How it works. And its impacts on the ocean. From the Arctic Monitoring and Assessment Programme.
AMAP is one of five Working Groups of the Arctic Council.
The primary function of AMAP is to advise the governments of the eight Arctic countries (Canada, Denmark/Greenland, Finland, Iceland, Norway, Russia, Sweden and the United States) on matters relating to threats to the Arctic region from pollution, and associated issues.
Scenes between man and nature - ‘Paths’ by Ruben Brulat
Photographer Ruben Brulat has traveled from Europe to Asia by land only, through Iraq, Iran, on-to Afghanistan, Tibet until Indonesia, Japan and Mongolia to complete his latest works titled ‘Paths’. Performing sometimes in welcoming sand, sometimes in the harsh snow, the series of images capture a concurrence between man and nature - as they let themselves go, opening up to their senses.
Types of Naturally Occurring Sinkholes
Sinkholes look dramatic when you’re peering down into one, but it’s below the surface where the real action takes place. A sinkhole’s identity centers on the gaps, crevices, cavities and voids that lie under the overburden, or the soil above the bedrock. As these gaps develop, expand and merge, soil from the overburden starts filling the void.
In the case of the sinkhole suddenly opening to swallow a car that we just mentioned, it formed because the overburden was no longer stable enough to hold itself up. This common type of sinkhole is known as a collapse or cover-collapse sinkhole. Although these sinkholes can appear suddenly, the erosion that makes them happen has likely been taking place for weeks or years before, underground and out of view. So let’s head underground.
The top layer of a cover-collapse sinkhole is usually a soft overburden, made of soil with a lot of clay in it. Over time, a small cavern forms underneath that soil. Opportunistic sediment takes advantage of the newly free real estate and starts spilling into the cavern — a process known as spalling. As spalling continues, the underground cavern fills with more sediment, hollowing out the space under the overburden. Eventually, the overburden becomes so thin that it suddenly collapses into the cavern below (this is the “cover collapse”), creating a sinkhole. In some cases, the cover can support its own weight but crumbles when additional weight, whether from a hapless person or car, passes over it.
With cover-subsidence sinkholes, water permeates the soft overburden. An example of this type of terrain is an overburden made up of up to 100 feet (30 meters) of sand with a small amount of clay below before yielding to soft limestone. As limestone dissolves and leaves a void, sediment from the overburden seeps in, creating a bowl-like impression in the Earth. These sinkholes, often only a few feet across and deep, are smaller than many others because after reaching a certain size, sand and sediment pour into the hole [source: Southwest Florida Water Management District]. This inflow of sediment can block the outflow of water by stopping up the cracks and passages that connect the sinkhole to underground conduits. Many of these sinkholes then become ponds, as the water has nowhere to drain. They also don’t produce the spectacular kind of cave-in associated with a cover-collapse sinkhole.
A dissolution or solution sinkhole is essentially a deep impression in the ground. These sinkholes usually have a thin overburden (if any), which washes away or is eroded. The now-exposed rock then progressively dissolves when it touches acidic water. The bare area hollows out, forming a shallow basin. Water often pools on the surface of a dissolution sinkhole, creating a sort of pond that compounds the erosion of rock below. Also, like in other types of sinkholes, objects and other material can get stuck in the fractures where water would normally flow out. Unlike a cover-subsidence sinkhole, there is no overburden or covering sediment to spall into the sinkhole or cover the eroding rock.
Sinkholes Caused by Humans
In urban settings in particular, sinkholes may owe their development to human activity as much as anything else. In some cases, sinkholes appear because of the combination of industrial activity or development, soft limestone bedrock and less than 200 feet (61 meters) of overburden [source: Southwest Florida Water Management District]. The following human actions can also cause sinkholes:
- Drilling and vibrations
- Mining
- Changes in weight
- Lots of foot or vehicle traffic
- Heavy increase in water flow, formation of a pond or body of water, or broken pipes, among other things
Sinkholes may also form in places where water flows regularly, such as a storm drain, or when water sources are diverted or cut off, especially by pumping out groundwater. A broken pipe can contribute to sinkhole development by flooding and weakening the soil, but it can also provide an outlet for the dirt and rock that’s supposed to surround pipes. After enough material falls into pipes and is transported away, the surrounding earth becomes destabilized, contributing to sinkhole formation, sewage or water spills, or other disasters…
May the 4th be with you…happy May 4th day
Nature’s first green is gold,
Her hardest hue to hold.
Her early leaf’s a flower;
But only so an hour.
Then leaf subsides to leaf.
So Eden sank to grief,
So dawn goes down to day.
Nothing gold can stay.
-Robert Frost
Historical Evolution of Style: Japan, Illustrations c.1868-1908 via The New York Public Library
Electronic zippers control DNA strands
A research team from NPL and the University of Edinburgh have invented a new way to zip and unzip DNA strands using electrochemistry.
The DNA double helix has been one of the most recognisable structures in science ever since it was first described by Watson and Crick almost 60 years ago (paper published in Nature in 25 April 1953). The binding and unbinding mechanism of DNA strands is vital to natural biological processes and to the polymerase chain reactions used in biotechnology to copy DNA for sequencing and cloning.
The improved understanding of this process, and the discovery of new ways to control it, would accelerate the development of new technologies such as biosensors and DNA microarrays that could make medical diagnostics cheaper, faster and simpler to use.
The most common way of controlling the binding of DNA is by raising and lowering temperature in a process known as heat cycling. While this method is effective, it requires bulky equipment, which is often only suitable for use in laboratories. Medicine is moving towards personalised treatment and diagnostics which require portable devices to quickly carry out testing at the point of care, i.e. in hospitals rather than laboratories. The development of alternative methods to control the DNA binding process, for example with changes in acidity or the use of chemical agents, would be a significant step towards lab-on-a-chip devices that can rapidly detect disease.
However, until now, no method has been shown to enable fast, electrochemical control at constant temperatures without the need for dramatic changes in solution conditions or modifying the nucleotides, the building blocks of DNA.
A research team from NPL and the University of Edinburgh have invented a new way of controlling DNA using electrochemistry. The team used a class of molecules called DNA intercalators which bind differently to DNA, depending on whether they are in a reduced or oxidised state, altering its stability. These molecules are also electroactive, meaning that their chemical state can be controlled with an electric current.
A paper published in the Journal of the American Chemical Society explains how the process works. Electrodes apply a voltage across a sample containing double strands of DNA which are bonded to the electroactive chemicals. This reduces the chemicals (they gain electrons), decreasing the stability of the DNA and unzipping the double helix into single strands. Removing the voltage leads to the oxidisation of the chemicals and the DNA strands zip back up to re-form the familiar double helix structure. Put simply, with the flick of a switch, the oxidation state of the molecules can be changed and the DNA strands are zipped together or pulled apart.
Psych-Quotes: How Color Influences Our Thinking →
Color actually influences the ways we think and this often occurs without our awareness. In my cognitive psychology class, my professor talked about a study where blue can cause us to feel more relaxed and think more creatively while red causes us to feel more alert and think…
‘Coelacanth’ Genome Unlocked
The genes of this fish, sometimes called a living fossil, reveal much about the origins of tetrapods, the evolutionary line that gave rise to amphibians, birds and mammals
The South African fisherman who pulled a prehistoric-looking blue creature out of his net in 1938 had unwittingly snagged one of the zoological finds of the century: a 1.5-meter-long coelacanth, a type of fish that had been thought to have become extinct 70 million years earlier.
Since then, scientists have identified two species of coelacanth, one African and one Indonesian. With their fleshy, lobed fins — complete with bones and joints — and round, paddle-like tails, they look strikingly similar to the coelacanths that lived during the Cretaceous period, when dinosaurs still roamed Earth.
Now, an international team of scientists has sequenced and analyzed the genome of the African coelacanth, Latimeria chalumnae; the findings are reported on page 311.
Like lungfish, the other surviving lineage of lobe-finned fishes, coelacanths are actually more closely related to humans and other mammals than to ray-finned fishes such as tuna and trout. Ancient lobe fins were the first vertebrates to brave the land, and the coelacanth genome is expected to reveal much about the origins of tetrapods, the evolutionary line that gave rise to amphibians, reptiles, birds and mammals, says lead author Chris Amemiya, a biologist at the University of Washington in Seattle. “The coelacanth is a cornerstone for our attempt to understand tetrapod evolution,” he says.
Korean Braised Beef Short Ribs with Steamed Rice and Salad
Ingredients:
2 lbs (about 1 kg) of beef short ribs – trim the fat off and cut the meat to the bones in squares
Water for boiling the ribs to remove the fat and blood
cooking wine - optional
3 tbsp soy sauce
black pepper to taste
1/2 tbsp brown sugar
4 cloves of Garlic
2 tbsp ginger
4 Green onion - chopped
1 large onion - chopped
2 Carrots - chopped
1 Korean radish or diakon or potato
1 bosc pears peeled and sliced
shiitake mushrooms – soaked, washed and sliced
2 eggs fried very thinly and rolled up and cut into threads for garnish
You can also use a slow cooker for this recipe
Directions:
1. Soak 5 shiitake mushrooms in warm water for about 4-6 hours.
2. Remove as much fat as you can from the meat then wash the short ribs in cold water and soak in a large bowl for at least 30 minutes.
3. Boil water in a large pot.
4. Put in the short ribs in the water and braise for 5-10 minutes.
5. Take the ribs out from the boiling water and wash them well under cold running water to remove unnecessary fat or floating bubbles.
6. Throw away the boiling water and clean the pot.
7. Place the clean beef short ribs in the pot.
8. Prepare a bowl to make seasoned water by mixing 2 cups of water, 3 tbsp soy sauce, 4 cloves of minced garlic), 1 sliced onion, 1 tbsp rice wine, and 1/2 tbsp brown sugar.
9. Alternatively you can blend all these ingredients in a food processor and add to the water.
10. Add it to the short ribs in the pot.
11. Boil it over medium heat for 20 minutes.
12. While it boils, you can prepare the other ingredients:
13. Cut carrot and radish into bite size pieces
14. Peel and cut the pears into chunks
15. Cut the soaked the shiitake mushrooms for about 30 min.
16. Let it simmer for about 1 hour over low heat.
17. Transfer the short ribs onto a platter
18. Mix 1 tbsp sesame oil, ½ tsp black pepper and squirt over the meat then garnish with the egg treads, sesame seeds, green onions and pine nuts.
19. Serve with fresh steamed rice and a side salad.
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