Posts tagged brain
Articles and news from the latest research reports.
Brain signal ID’s responders to fast-acting antidepressant
August 3, 2012
Scientists have discovered a biological marker that may help to identify which depressed patients will respond to an experimental, rapid-acting antidepressant. The brain signal, detectable by noninvasive imaging, also holds clues to the agent’s underlying mechanism, which are vital for drug development, say National Institutes of Health researchers.
Dr. Zarate views subject in MEG scanner from scanner control room.
The signal is among the latest of several such markers, including factors detectable in blood, genetic markers, and a sleep-specific brain wave, recently uncovered by the NIH team and grantee collaborators. They illuminate the workings of the agent, called ketamine, and may hold promise for more personalized treatment.
"These clues help focus the search for the molecular targets of a future generation of medications that will lift depression within hours instead of weeks," explained Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health (NIMH). "The more precisely we understand how this mechanism works, the more narrowly treatment can be targeted to achieve rapid antidepressant effects and avoid undesirable side effects."
Zarate, Brian Cornwell, Ph.D., and NIMH colleagues report on their brain imaging study online in the journal Biological Psychiatry.
Previous research had shown that ketamine can lift symptoms of depression within hours in many patients. But side effects hamper its use as a first-line medication. So researchers are studying its mechanism of action in hopes of developing a safer agent that works similarly.
Ketamine works through a different brain chemical system than conventional antidepressants. It initially blocks a protein on brain neurons, called the NMDA receptor, to which the chemical messenger glutamate binds. However, it is not known if the drug’s rapid antidepressant effects are a direct result of this blockage or of downstream effects triggered by the blockage, as suggested by animal studies.
To tease apart ketamine’s workings, the NIMH team imaged depressed patients’ brain electrical activity with magnetoencephalography (MEG). They monitored spontaneous activity while subjects were at rest, and activity evoked by gentle stimulation of a finger, before and 6.5 hours after an infusion of ketamine.
It was known that by blocking NMDA receptors, ketamine causes an increase in spontaneous electrical signals, or waves, in a particular frequency range in the brain’s cortex, or outer mantle. Hours after ketamine administration— in the timeframe in which ketamine relieves depression — spontaneous electrical activity in people at rest was the same whether or not the drug lifted their depression.
Electrical activity evoked by stimulating a finger, however, was different in the two groups. MEG imaging made it possible to monitor excitability of the somatosensory cortex, the part of the cortex that registers sensory stimulation. Those who responded to ketamine showed an increased response to the finger stimulation, a greater excitability of the neurons in this part of the cortex.
Such a change in excitability is likely to result, not from the immediate effects of blocking the receptor, but from other processes downstream, in the cascade of effects set in motion by NMDA blockade, say the researchers. Evidence points to changes in another type of glutamate receptor, the AMPA receptor, raising questions about whether the blocking of NMDA receptors is even necessary for ketamine’s antidepressant effect. If NMDA blockade is just a trigger, then targeting AMPA receptors may prove a more direct way to effect a lifting of depression.
While antipsychotic drugs alleviate the symptoms of many people with schizophrenia, around a third of patients resist such treatments. A new study, led by Javier Gonzalez-Maeso of the Mount Sinai School of Medicine, suggests that this frustrating intractability depends on how DNA is packaged.
Gonzalez-Maeso and his colleagues found that antipsychotic drugs can suppress the expression of glutamate receptors in the brain, stunting their effectiveness as treatments for schizophrenia. But the researchers also found a way of boosting the effects of antipsychotics—by pairing them with drugs that block the gene suppression pathway.
Schizophrenia
Credit: JOHN BAVOSI/SCIENCE PHOTO LIBRARY
Caption: Schizophrenia. Artwork of a man hearing non- existent women’s voices. Auditory hallucinations are one of the most common symptoms of schizophrenia. One explanation for this disease is known as the dopamine hypothesis. Dopamine (the molecules at lower left & right) is a type of neurotransmitter. This chemical (tiny red spheres) is released from the ends (synapses) of nerve cells (neurons, upper left & right) when they pass on nerve impulses to other neurons. In schizophr- enia, however, the dopamine-producing neurons of the brain are overactive. This causes the sufferer to lose contact with reality, suffering from confused thoughts and emotional responses.
3D reconstruction of Phineas Gage’s skull, showing the passage of the tamping iron. Read about Gage’s connectome here
The World’s Most Famous Brain
In the summer of 1953, Henry Gustav Molaison (1926-2008) underwent brain surgery to contain epileptic seizures that had become critically debilitating. The intervention brought some relief from convulsions, but these positive results were overshadowed by an astonishing and indelible side effect. Soon after the operation, it became apparent that he could no longer recognize hospital staff, he did not remember the way home, he did not remember newspaper articles he had just read, nor the crossword puzzles he had solved; otherwise, he was completely normal. Since the time of the surgery, more than five decades of scrupulous neuropsychological research examined the nature of patient H.M.’s amnesia which proved to be both persistent and remarkably selective.
The goal of our project is to provide a window into the brain of the man who helped establish the scientific study of memory and unfailingly forgot the enormously generous contribution he made to medical research.
The rat brain has served as an excellent model for elucidating the complex anatomy and physiological mechanisms of the human brain. As a result, a significant amount of information on brain diseases, such as dementia and Parkinson’s disease, has been determined from investigations using rat brains.
Fragile X and Down Syndromes Share Signalling Pathway for Intellectual Disability
"We have shown for the first time that some of the proteins altered in Fragile X and Down syndromes are common molecular triggers of intellectual disability in both disorders," said Kyung-Tai Min, one of the lead authors of the study and a professor at Indiana University and the Ulsan National Institute of Science and Technology in Korea. "Specifically, two proteins interact with each other in a way that limits the formation of spines or protrusions on the surface of dendrites." He added: "These outgrowths of the cell are essential for the formation of new contacts with other nerve cells and for the successful transmission of nerve signals. When the spines are impaired, information transfer is impeded and mental retardation takes hold."
'Inattention blindness' due to brain load
“Engaging attention on a high load task has a strong effect on the brain’s response to the rest of the world,” says Professor Nilli Lavie of the UCL Institute of Cognitive Neuroscience.
"It reduces both the level and precision, or ‘tuning’, of neural response to anything else around us that is not part of the task. "These effects of load on neural response explain inattentional blindness. Although our environment hasn’t changed, the change in our brain response under load leads to inability to perceive otherwise perfectly visible stimuli outside our focus of attention,” she explains.
New statistical method provides way to analyze synchronized neural activity in animals
The synchronized electrical activity of multiple neurons gives rise to coordinated network activity. This cooperative activity is highly dynamic and widely thought to be critical for organization behavior and cognitive processes.
Current methods for the statistical analysis of synchronized activity can analyze pairs of cells or detect the existence of correlations between multiple neurons. However, there is no way of accurately determining specific groups of neurons that interact with each other, and how this activity changes with time.
Irony seen through the eye of MRI
A French team has shown that the activation of the ToM neural network increases when an individual is reacting to ironic statements. Published in Neuroimage, these findings represent an important breakthrough in the study of Theory of Mind and linguistics, shedding light on the mechanisms involved in interpersonal communication.
In our communications with others, we are constantly thinking beyond the basic meaning of words. For example, if asked, “Do you have the time?” one would not simply reply, “Yes.” The gap between what is said and what it means is the focus of a branch of linguistics called pragmatics. In this science, “Theory of Mind” (ToM) gives listeners the capacity to fill this gap. In order to decipher the meaning and intentions hidden behind what is said, even in the most casual conversation, ToM relies on a variety of verbal and non-verbal elements: the words used, their context, intonation, “body language,” etc.