Posts Tagged ‘epilepsy’

1-alzheimersdi
Diagram of the brain of a person with Alzheimer’s Disease.

In recent years, researchers have largely converged on the role of inflammation in the development and progression of Alzheimer’s disease (AD). Studies over the past decade have revealed unexpected interactions between the brain and the immune system, and metabolic conditions such as obesity and diabetes may activate inflammatory responses that contribute to the development and progression of AD.

The activation of the inflammatory response is controlled by the inflammasome, a multi-protein oligomer that promotes the release of several pro-inflammatory cytokines including interleukin 1β (IL-1β) and interleukin 18 (IL-18). In an earlier study, a group of researchers with the University of Massachusetts Medical School, the University of Tokyo and the University of Bonn reported that mice with a cognate of Alzheimer’s disease that were additionally bred to knock out the NLRP3 gene encoding the inflammasome were completely protected from neurodegenerative effects of the disease. The researchers presumed that this was the result of their inability to produce IL-1β and IL-18.

This finding was quite promising, suggesting that targeting components of the inflammasome might be a path to Alzheimer’s treatments. In their new study, they sought to determine the effect of IL-18 by breeding IL-18 knockout mice. The researchers considered IL-18 to be a promising target, because levels are elevated in the cerebrospinal fluid of AD patients with mild cognitive impairment. Additionally, it is known to increase the production of amyloid peptide.

But the result of the new mouse study was startling, and completely unprecedented in Alzheimer’s research. The IL-18 knockout mice developed a lethal seizure disorder that the researchers attribute to an increase in neuronal network transmission. The authors write, “… the effects of IL-18 deletion were so dramatic that we were unable to identify previous evidence to help understand the phenomena.”

The finding that a proinflammatory cytokine might in some way ameliorate seizure-inducing neural activity seems counterintuitive, since inflammation is theorized to promote neurodegenerative symptoms in AD. The researchers believe that epilepsy is understudied in AD patients, even though it is a common complication; they point out that two-thirds of AD patients experience both motor and non-motor seizures. Additionally, AD patients with epilepsy are more likely to develop memory loss and other cognitive symptoms, and experience a more widespread loss of brain cells than AD patients without epilepsy, according to the researchers.

They theorize that IL-18 may be counteracting seizure-promoting effects of IL-1β, and suppressing IL-18 thus induced seizures in the test mice. “In fact,” they write, “the countereffect of IL-18 and IL-1β has been documented in a mouse model of cerebellar ataxia. Importantly, we found that the acute application of IL-18 protein reduced excitatory synaptic transmission in the hippocampus, providing evidence that IL-18 has a protective function in neuronal excitability. Thus, we speculate that IL-18 directly suppresses these proepileptogenic effects of IL-1β in APP/PS1 mice.”

However, the most important implication of the study may be that, while the inflammasome is a promising therapeutic target for Alzheimer’s, inhibiting specific cytokines could negatively affect people with the disease.

More information: Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice. Proceedings of the National Academy of Sciences (2018). doi.org/10.1073/pnas.1801802115

Abstract
Alzheimer’s disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1ΔE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1β or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD.
Journal reference: Proceedings of the National Academy of Sciences

ONE moment you’re conscious, the next you’re not. For the first time, researchers have switched off consciousness by electrically stimulating a single brain area.

Scientists have been probing individual regions of the brain for over a century, exploring their function by zapping them with electricity and temporarily putting them out of action. Despite this, they have never been able to turn off consciousness – until now.

Although only tested in one person, the discovery suggests that a single area – the claustrum – might be integral to combining disparate brain activity into a seamless package of thoughts, sensations and emotions. It takes us a step closer to answering a problem that has confounded scientists and philosophers for millennia – namely how our conscious awareness arises.

Many theories abound but most agree that consciousness has to involve the integration of activity from several brain networks, allowing us to perceive our surroundings as one single unifying experience rather than isolated sensory perceptions.

One proponent of this idea was Francis Crick, a pioneering neuroscientist who earlier in his career had identified the structure of DNA. Just days before he died in July 2004, Crick was working on a paper that suggested our consciousness needs something akin to an orchestra conductor to bind all of our different external and internal perceptions together.

With his colleague Christof Koch, at the Allen Institute for Brain Science in Seattle, he hypothesised that this conductor would need to rapidly integrate information across distinct regions of the brain and bind together information arriving at different times. For example, information about the smell and colour of a rose, its name, and a memory of its relevance, can be bound into one conscious experience of being handed a rose on Valentine’s day.

The pair suggested that the claustrum – a thin, sheet-like structure that lies hidden deep inside the brain – is perfectly suited to this job (Philosophical Transactions of The Royal Society B, doi.org/djjw5m).

It now looks as if Crick and Koch were on to something. In a study published last week, Mohamad Koubeissi at the George Washington University in Washington DC and his colleagues describe how they managed to switch a woman’s consciousness off and on by stimulating her claustrum. The woman has epilepsy so the team were using deep brain electrodes to record signals from different brain regions to work out where her seizures originate. One electrode was positioned next to the claustrum, an area that had never been stimulated before.

When the team zapped the area with high frequency electrical impulses, the woman lost consciousness. She stopped reading and stared blankly into space, she didn’t respond to auditory or visual commands and her breathing slowed. As soon as the stimulation stopped, she immediately regained consciousness with no memory of the event. The same thing happened every time the area was stimulated during two days of experiments (Epilepsy and Behavior, doi.org/tgn).
To confirm that they were affecting the woman’s consciousness rather than just her ability to speak or move, the team asked her to repeat the word “house” or snap her fingers before the stimulation began. If the stimulation was disrupting a brain region responsible for movement or language she would have stopped moving or talking almost immediately. Instead, she gradually spoke more quietly or moved less and less until she drifted into unconsciousness. Since there was no sign of epileptic brain activity during or after the stimulation, the team is sure that it wasn’t a side effect of a seizure.

Koubeissi thinks that the results do indeed suggest that the claustrum plays a vital role in triggering conscious experience. “I would liken it to a car,” he says. “A car on the road has many parts that facilitate its movement – the gas, the transmission, the engine – but there’s only one spot where you turn the key and it all switches on and works together. So while consciousness is a complicated process created via many structures and networks – we may have found the key.”

Counter-intuitively, Koubeissi’s team found that the woman’s loss of consciousness was associated with increased synchrony of electrical activity, or brainwaves, in the frontal and parietal regions of the brain that participate in conscious awareness. Although different areas of the brain are thought to synchronise activity to bind different aspects of an experience together, too much synchronisation seems to be bad. The brain can’t distinguish one aspect from another, stopping a cohesive experience emerging.

Since similar brainwaves occur during an epileptic seizure, Koubeissi’s team now plans to investigate whether lower frequency stimulation of the claustrum could jolt them back to normal. It may even be worth trying for people in a minimally conscious state, he says. “Perhaps we could try to stimulate this region in an attempt to push them out of this state.”

Anil Seth, who studies consciousness at the University of Sussex, UK, warns that we have to be cautious when interpreting behaviour from a single case study. The woman was missing part of her hippocampus, which was removed to treat her epilepsy, so she doesn’t represent a “normal” brain, he says.

However, he points out that the interesting thing about this study is that the person was still awake. “Normally when we look at conscious states we are looking at awake versus sleep, or coma versus vegetative state, or anaesthesia.” Most of these involve changes of wakefulness as well as consciousness but not this time, says Seth. “So even though it’s a single case study, it’s potentially quite informative about what’s happening when you selectively modulate consciousness alone.”

“Francis would have been pleased as punch,” says Koch, who was told by Crick’s wife that on his deathbed, Crick was hallucinating an argument with Koch about the claustrum and its connection to consciousness.

“Ultimately, if we know how consciousness is created and which parts of the brain are involved then we can understand who has it and who doesn’t,” says Koch. “Do robots have it? Do fetuses? Does a cat or dog or worm? This study is incredibly intriguing but it is one brick in a large edifice of consciousness that we’re trying to build.”

http://www.newscientist.com/article/mg22329762.700-consciousness-onoff-switch-discovered-deep-in-brain.html?full=true#.U7n7sI1dVC8

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

brain

The many documented cases of strange delusions and neurological syndromes can offer a window into how bizarre the brain can be.

It may seem that hallucinations are random images that appear to some individuals, or that delusions are thoughts that arise without purpose. However, in some cases, a specific brain pathway may create a particular image or delusion, and different people may experience the same hallucination.

In recent decades, with advances in brain science, researchers have started to unravel the causes of some of these conditions, while others have remained a mystery.

Here is a look at seven odd hallucinations, which show that anything is possible when the brain takes a break from reality.

1. Alice-in-Wonderland syndrome
This neurological syndrome is characterized by bizarre, distorted perceptions of time and space, similar to what Alice experienced in Lewis Carroll’s “Alice’s Adventures in Wonderland.”

Patients with Alice-in-Wonderland syndrome describe seeing objects or parts of their bodies as smaller or bigger than their actual sizes, or in an altered shape. These individuals may also perceive time differently.

The rare syndrome seems to be caused by some viral infections, epilepsy, migraine headaches and brain tumors. Studies have also suggested that abnormal activity in parts of the visual cortex that handle information about the shape and size of objects might cause the hallucinations.

It’s also been suggested that Carroll himself experienced the condition during migraine headaches and used them as inspiration for writing the tale of Alice’s strange dream.

English psychiatrist John Todd first described the condition in an article published in the Canadian Medical Association Journal in 1955, and that’s why the condition is also called Todd’s syndrome. However, an earlier reference to the condition appears in a 1952 article by American neurologist Caro Lippman. The doctor describes a patient who reported feeling short and wide as she walked, and referenced “Alice’s Adventures in Wonderland” to explain her body image illusions.

2. Walking Corpse Syndrome
This delusion, also called Cotard’s Syndrome, is a rare mental illness in which patients believe they are dead, are dying or have lost their internal organs.

French neurologist Jules Cotard first described the condition in 1880, finding it in a woman who had depression and also symptoms of psychosis. The patient believed she didn’t have a brain or intestines, and didn’t need to eat. She died of starvation.

Other cases of Cotard’s syndrome have been reported in people with a range of psychiatric and neurological problems, including schizophrenia, traumatic brain injury and multiple sclerosis.

In a recent case report of Cotard’s syndrome, researchers described a previously healthy 73-year-old woman who went to the emergency room insisting that she was “going to die and going to hell.” Eventually, doctors found the patient had bleeding in her brain due to a stroke. After she received treatment in the hospital, her delusion resolved within a week, according to the report published in January 2014 in the journal of Neuropsychiatry.

3. Charles Bonnet syndrome
People who have lost their sight may develop Charles Bonnet syndrome, which involves having vivid, complex visual hallucinations of things that aren’t really there.

People with this syndrome usually hallucinate people’s faces, cartoons, colored patterns and objects. It is thought the condition occurs because the brain’s visual system is no longer receiving visual information from the eye or part of the retina, and begins making up its own images.

Charles Bonnet syndrome occurs in between 10 and 40% of older adults who have significant vision loss, according to studies.

4. Clinical lycanthropy
In this extremely rare psychiatric condition, patients believe they are turning into wolves or other animals. They may perceive their own bodies differently, and insist they are growing the fur, sharp teeth and claws of a wolf.

Cases have also been reported of people with delusional beliefs about turning into dogs, pigs, frogs and snakes.

The condition usually occurs in combination with another disorder, such as schizophrenia, bipolar disorder or severe depression, according to a review study published in the March issue of the journal History of Psychiatry in 2014.

5. Capgras delusion
Patients with Capgras delusion believe that an imposter has replaced a person they feel close to, such as a friend or spouse. The delusion has been reported in patients with schizophrenia, Alzheimer’s disease, advanced Parkinson’s disease, dementia and brain lesions.

One brain imaging study suggested the condition may involve reduced neural activity in the brain system that processes information about faces and emotional responses.

6. Othello syndrome
Named after Shakespeare’s character, Othello syndrome involves a paranoid belief that the sufferer’s partner is cheating. People with this condition experience strong obsessive thoughts and may show aggression and violence.

In one recent case report, doctors described a 46-year-old married man in the African country Burkina Faso who had a stroke, which left him unable to communicate and paralyzed in half of his body. The patient gradually recovered from his paralysis and speaking problems, but developed a persistent delusional jealousy and aggression toward his wife, accusing her of cheating with an unidentified man.

7. Ekbom’s syndrome
Patients with Ekbom’s syndrome, also known as delusional parasitosis or delusional infestations, strongly believe they are infested with parasites that are crawling under their skin. Patients report sensations of itching and being bitten, and sometimes, in an effort to get rid of the pathogens, they may hurt themselves, which can result in wounds and actual infections.

It’s unknown what causes these delusions, but studies have linked the condition with structural changes in the brain, and some patients have improved when treated with antipsychotic medications.

http://www.livescience.com/46477-oddest-hallucinations.html