Neurophysiology Laboratory

CIMA, Spain

Neurophysiology Laboratory

CIMA, Spain
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News Article | February 20, 2017

Findings show how the brain's cells create and recall memories, giving boost to development of treatments for memory disorders LOS ANGELES - Cedars-Sinai neuroscientists have uncovered processes involved in how the human brain creates and maintains short-term memories. "This study is the first clear demonstration of precisely how human brain cells work to create and recall short-term memories," said Ueli Rutishauser, PhD, associate professor of Neurosurgery in the Cedars-Sinai Department of Neurosurgery and the study's senior author. "Confirmation of this process and the specific brain regions involved is a critical step in developing meaningful treatments for memory disorders that affect millions of Americans." The study's findings, published online Feb. 20 and in the April print edition of Nature Neuroscience, involve a type of brain cell, called a persistently active neuron, that is vital for supporting short-term memory. Results indicate that this specific type of neurons remain active for several seconds when a person is required to memorize an object or image and recall it at a later time. The findings reveal critical new information on how the human brain stores and maintains short-term memories - the ability to remember ideas, thoughts, images and objects during a time frame of seconds to minutes. Short-term memory is essential for making decisions and mental calculations. "Because impaired short-term memory severely weakens someone's ability to complete everyday tasks, it is essential to develop a better understanding of this process so new treatments for memory disorders can be developed," said Jan Kami?ski, PhD, a neuroscientist at Cedars-Sinai and lead author of the study. Researchers found persistently active neurons in the medial frontal lobe as well as the medial temporal lobe. The neurons remained active even after the patient stopped looking at an image or object. Until now, the medial temporal lobe was thought to be involved only in the formation of new long-term memories. Now, however, the new findings show that both areas of the brain are critical for maintaining short-term memory and rely upon the ongoing activity of the neurons for memorization. During the study, a team of Cedars-Sinai neurosurgeons implanted electrodes to precisely locate the source of seizures in 13 epilepsy patients. Investigators then studied the electrical activity of individual neurons while patients performed a memory test. During the test, patients viewed a sequence of three images, followed by a two-to-three-second delay. Then patients were shown another image and were asked to decide whether they had previously seen the image. "A surprising finding of this new study is that some of the persistently active neurons were only active if the patient memorized a specific image," Kami?ski said. "For example, the researchers discovered a neuron that reacted every time the patient memorized an image of Han Solo, a character in the movie Star Wars, but not any other memory." Another key finding of the study was a correlation between the strength of the neurons' activity and the ability to later make use of the memory. "We noticed that the larger the increase in activity, the more likely the patient was to remember the image. In contrast, if the neuron's activity was weak, the patient forgot the image and thus lost the memory," said Adam N. Mamelak, MD, professor of Neurosurgery, director of Functional Neurosurgery at Cedars-Sinai and a co-author of the study. Keith L. Black, MD, chair of the Department of Neurosurgery at Cedars-Sinai, said the breakthrough can be credited to the partnership between neurosurgery and neurology clinicians working with neuroscientists. "This unique collaboration allows us to discover the mechanisms of memory in the human brain," Black said. "This is key for moving closer to finding treatments for memory disorders, epilepsy and other diseases." Rutishauser said a next step is understanding how multiple areas of the brain work together to support short-term memory. "Now that specific neurons that support short-term memory have been discovered, we have a way to study their interaction systematically," he said. Other Cedars-Sinai study contributors included Jeffrey Chung, MD, director of the Epilepsy Program and the Neurophysiology Laboratory; and Shannon Sullivan, research associate. Ian Ross, MD, a neurosurgeon at Huntington Memorial Hospital also contributed. This work was supported by National Science Foundation grant 1554105, National Institute of Mental Health grant R01MH110831, the McKnight Endowment Fund for Neuroscience, a NARSAD Young Investigator grant from the Brain & Behavior Research Foundation (23502), and the Pfeiffer Foundation.

Chavez M.,French National Center for Scientific Research | De Vico Fallani F.,French National Center for Scientific Research | De Vico Fallani F.,University of Rome La Sapienza | De Vico Fallani F.,Neuroelectrical Imaging and BCI Laboratory | And 6 more authors.
Neuroinformatics | Year: 2013

Recent findings suggest that the preparation and execution of voluntary self-paced movements are accompanied by the coordination of the oscillatory activities of distributed brain regions. Here, we use electroencephalographic source imaging methods to estimate the cortical movement-related oscillatory activity during finger extension movements. Then, we apply network theory to investigate changes (expressed as differences from the baseline) in the connectivity structure of cortical networks related to the preparation and execution of the movement. We compute the topological accessibility of different cortical areas, measuring how well an area can be reached by the rest of the network. Analysis of cortical networks reveals specific agglomerates of cortical sources that become less accessible during the preparation and the execution of the finger movements. The observed changes neither could be explained by other measures based on geodesics or on multiple paths, nor by power changes in the cortical oscillations. © 2013 Springer Science+Business Media New York.

Perez-Alcazar M.,Neurophysiology Laboratory | Nicolas M.J.,Neurophysiology Laboratory | Valencia M.,Neurophysiology Laboratory | Alegre M.,Neurophysiology Laboratory | And 3 more authors.
Brain Research | Year: 2010

There has been a growing interest during the last years on the relationship between Parkinson's disease and changes in the oscillatory activity, mostly in the cortico-basal motor loop. As Parkinson's disease (PD) is not limited to motor symptoms, it is logical to assume that the changes in oscillatory activity are not limited to this loop. Steady-state responses (SSR) are the result of averaging individual responses to trains of rhythmic stimuli delivered at a constant frequency. The amplitude of the response varies depending on the stimulus modality and stimulation rate, with a frequency of maximal response that is probably associated to the working frequency of the pathway involved. The study of SSR may be of interest in PD as a non-invasive test of cortical oscillatory activity. Our aim was to study the changes in auditory steady-state responses (ASSR) in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease in rats. We recorded the ASSR over the auditory cortex in a group of 10 control and 17 6-OHDA lesioned rats (the latter before and after the administration of the dopaminergic agonist apomorphine) both awake and under anesthesia with ketamine/xylazine, using chirp-modulated stimuli. The three conditions (control, lesion, lesion plus apomorphine) were compared with special emphasis on the amplitude, inter-trial phase coherence, and frequency of maximal response. A reduction in the frequency of maximal response (between 40 and 60 Hz) was observed in the 6-OHDA lesioned rats that was normalized after apomorphine injection. The administration of this dopaminergic agonist also reduced the inter-trial phase coherence of the response in frequencies above 170 Hz. These findings suggest that the nigrostriatal dopaminergic system may be involved in the regulation of oscillatory activity not only in motor circuits, but also in sensory responses. © 2009 Elsevier B.V. All rights reserved.

Pisani V.,University of Rome Tor Vergata | Pisani V.,Neurophysiology Laboratory | Madeo G.,University of Rome Tor Vergata | Madeo G.,Neurophysiology Laboratory | And 10 more authors.
Movement Disorders | Year: 2011

Endocannabinoids (eCBs) are endogenous lipids that bind principally type-1 and type-2 cannabinoid (CB1 and CB2) receptors. N-Arachidonoylethanolamine (AEA, anandamide) and 2-arachidonoylglycerol (2-AG) are the best characterized eCBs that are released from membrane phospholipid precursors through multiple biosynthetic pathways. Together with their receptors and metabolic enzymes, eCBs form the so-called 'eCB system'. The later has been involved in a wide variety of actions, including modulation of basal ganglia function. Consistently, both eCB levels and CB1 receptor expression are high in several basal ganglia regions, and more specifically in the striatum and in its target projection areas. In these regions, the eCB system establishes a close functional interaction with dopaminergic neurotransmission, supporting a relevant role for eCBs in the control of voluntary movements. Accordingly, compelling experimental and clinical evidence suggests that a profound rearrangement of the eCB system in the basal ganglia follows dopamine depletion, as it occurs in Parkinson's disease (PD). In this article, we provide a brief survey of the evidence that the eCB system changes in both animal models of, and patients suffering from, PD. A striking convergence of findings is observed between both rodent and primate models and PD patients, indicating that the eCB system undergoes dynamic, adaptive changes, aimed at restoring an apparent homeostasis within the basal ganglia network. © 2010 Movement Disorder Society.

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