Sunday, July 31, 2005

Synapse-Associated Protein 97 (SAP97): PDZ1

From a Brown University press release (the press release includes a graphic showing a portion of the protein):
Researchers Reveal Secret of Key Protein in Brain and Heart Function

29 July 2005

Brown University researchers have solved the structure of a critical piece of SAP97, a protein used to keep hearts beating and brains learning. Results, reported by Dale Mierke in The Journal of Biological Chemistry, put science a step closer to understanding how this protein aids in brain and heart function.

PROVIDENCE, R.I. — Brown University biologists have solved the structure of a critical piece of synapse-associated protein 97 (SAP97) found in abundance in the heart and head, where it is believed to play a role in everything from cardiac contractions to memory creation. Results are published in The Journal of Biological Chemistry.

Dale Mierke, associate professor of medical science at Brown, said that knowing how a piece of SAP97 is built is an important step. Now that part of the protein’s structure is solved, scientists can create a molecule to disable it. That, in turn, will allow them to fully understand SAP97’s role in the body. And that will point drug makers to targets for developing new ways to treat cardiac or neurological diseases.

“To arrive at a solution, you need to understand the problem,” Mierke said. “Solving protein structures opens doors for effective treatments.”

SAP97 is found mainly in the central nervous system and is known as a “scaffolding” protein. In this role, it serves as a sort of tether, grabbing proteins inside the cell critical to nerve signaling and keeping them close to N-methyl-D-asparate (NMDA) receptors at the cell surface. NMDA receptors help usher in a neurotransmitter called glutamate that is essential for learning and memory and also plays a role in drug addiction. A similar scaffolding mechanism is at work in the heart, where it affects basic functions, including the heartbeat.
[ ... Read the full press release ... ]
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The researchers examined the portion of the protein known as PDZ1, which is where the protein links to NMDA receptors.
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Anthony H. Risser | | |

Friday, July 29, 2005

What is Neuropsychology?

A number of years ago, I wrote a short piece about the profession of neuropsychology for one of those regional hospital and medical-center monthly newspapers (the kind you can find stacked up at entrances to various medical facilities). I revised it a bit and posted it on my website several years ago. It remains there, should you need an answer to this question: "What is Neuropsychology?"
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Anthony H. Risser | | |

Thursday, July 28, 2005

Buildings and Brains

Aalia Wayfare's Radio Weblog points to an interesting article about the use of neuroscientific principles in architectual design in its post: Neuroscience and Architecture.

Architectual niche interest in brain function, health, and disease, goes back at least twenty years (if not longer) in the design of, for example, hospitals and living facilities for those with Alzheimer disease and other dementia-causing neurodegenerative processes. This interest has yet to become a mainstream one in the profession. However, interest continues to grow.

The article pointed to above provides a decent overview.

Visit the Academy of Neuroscience for Architecture for additional information.
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Anthony H. Risser | | |

Wednesday, July 27, 2005

Remyelination: Therapeutic Approach Combining Stem Cells and D15A Gene Therapy

A press release from the National Institutes of Health (NIH):

Combination Therapy Leads to Partial Recovery from Spinal Cord Injury in Rats

NIH News
National Institutes of Health
Tuesday, July 26, 2005, 5:00 p.m. ET

CONTACT: Natalie Frazin, Paul Girolami, 301-496-5924

Combining partially differentiated stem cells with gene therapy can promote the growth of new "insulation" around nerve fibers in the damaged spinal cords of rats, a new study shows. The treatment, which mimics the activity of two nerve growth factors, also improves the animals' motor function and electrical conduction from the brain to the leg muscles. The finding may eventually lead to new ways of treating spinal cord injury in humans. The study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

The new study provides the best demonstration to date that producing a nerve-insulating substance called myelin can lead to functional improvements in animals with spinal cord injury. Previous studies have shown that the loss of myelin around nerve fibers contributes to the impaired function after a spinal cord injury. However, until now it has not been clear whether promoting new myelin growth in the spinal cord can reverse this damage, says Scott R. Whittemore, Ph.D., of the University of Louisville in Kentucky, who led the new study. "Many other investigators have suggested that remyelination is a possible approach to repair the spinal cord, but this is the first study to show unequivocally that it works," says Dr. Whittemore. "It is a proof of principle." Although the finding is promising, much work remains before such a technique could be used in humans. The study appears in the July 27, 2005, issue of the Journal of Neuroscience.

In the study, the researchers took special cells called glial-restricted precursors from the spinal cords of embryonic rats. These precursor cells develop from stem cells and are specialized so that they can form only two kinds of cells: astrocytes, which help support neurons and influence their activity, and oligodendrocytes, which produce myelin. The scientists used a modified virus to insert genes for marker proteins that make the cells visible. Some cells also received a gene called D15A. This gene produces a protein with activity similar to growth factors called neurotrophin 3 (NT3) and brain-derived neurotrophic factor (BDNF). Both NT3 and BDNF help myelin-producing cells (oligodendrocytes) develop and survive.

Dr. Whittemore and his colleagues injected the treated precursor cells into the spinal cords of rats with a type of spinal injury called a contusion, which is caused by an impact to the spinal cord. Other groups of spinal cord-injured rats received just precursor cells, D15A gene therapy, or other treatments that were used for comparison. The rats were evaluated weekly for 6 weeks after the treatment using a behavioral test called the Basso-Beattie-Bresnahan scale, which measures characteristics such as weight support, joint movements, and coordination. The researchers also used an electrical current test in which they put a magnetic stimulator on the skull and measured whether the resulting electrical current was transmitted to a muscle in one of the hind legs.

Most of the rats treated with the combination of precursor cells and gene therapy improved significantly on both tests, the researchers found. The combination therapy led to an improvement in the rats' ability to walk and about a 10 percent improvement on the electrical current test. Rats that received the other treatments did not improve significantly, and untreated rats did not have any electrical activity that passed through the damaged spinal cord. Studies of the damaged spinal cord tissue after the combined treatment showed that many of the transplanted cells survived and migrated within the cord and that about 30 percent of them developed into myelin-producing oligodendrocytes.

"The key word here is 'combination.' This is one of a series of new studies showing that a combination of therapies is needed for successful spinal repair, in this case, specialized cells and growth factors. The experiments also used a combination of outcomes — physiology, behavior, and anatomy — to point clearly at myelination as the cause for improved function," says Naomi Kleitman, Ph.D., the NINDS program director for the grants that funded this work. "The study also is a good example of strong collaboration between two spinal cord injury research centers, one at the University of Louisville and the other at the University of Miami in Florida."
[ ... Read the full press release ... ]
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The paper's full reference is:
Cao Q, Xu X-M, DeVries WH, Enzmann GU, Ping P, Tsoulfas P, Wood PM, Bunge MB, Whittemore SR. Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. Journal of Neuroscience, July 27, 2005, Vol. 25, No. 30, pp. 6947-6957.
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Anthony H. Risser | | |

Business World: "The Brain Industry"

From The Seattle Times:
Biotech Watch: Biotech companies scramble to develop brain-related products
By Steve Johnson
Knight Ridder Newspapers
The Seattle Times
Monday, July 25, 2005

SAN JOSE, Calif. — The prospect of a billion people nearing the age when they risk brain-related illnesses like Alzheimer's disease or chronic pain is helping fuel a costly scramble by biotechnology firms to find solutions.

The San Francisco Bay Area has more than 30 companies, out of about 300 worldwide, developing brain-related products for everything from sleep and anxiety disorders to multiple sclerosis and stroke. Much of the focus of "the brain industry," as it is dubbed, is on finding treatments for ailments likely to hit aging baby boomers.
[ ... Read the full article ... ]

The article discusses some successes and challenges to success in this field, including vignettes about Saegis Pharmaceuticals (Alzheimer disease and cognitive loss), Micrus Endovascular (surgical interventions), BioCentral Systems, and Pain Therapeutics.
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Anthony H. Risser | | |

Recognition at the Mirror

From The New York Times:
Who's That Strange Monkey in the Mirror?
By NICHOLAS WADE
The New York Times
Published: July 26, 2005

Humans, the great apes and, probably, dolphins share an intellectual skill unusual in the animal world: they recognize their own reflections in a mirror.

Capuchin monkeys, a new study says, understand that the image in the mirror is not a stranger, but they don't know it's their own.

That ability seems to mark a bright line between these species and monkeys, who, scientists have long assumed, look into mirrors and see only strangers. But a monkey's reaction to its reflection is more complex than is generally assumed, said Frans de Waal of the Yerkes National Primate Research Center in Atlanta.

Dr. de Waal and his colleagues were able to test the widely held belief that monkeys see strangers in the mirror using two troops of tufted capuchin monkeys at the Yerkes Center that had never met each other.

The capuchins, the Yerkes team is reporting today, understood at once that the mirror image was not a stranger, even though they failed to recognize themselves in the image. The findings appeared last week in The Proceedings of the National Academy of Sciences.
[ ... Read the full article ... ]

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Anthony H. Risser | | |

Monday, July 25, 2005

Abstract of the Day: Frontal Lobe Functioning

Ardesheer Talati and Joy Hirsch. Functional Specialization within the Medial Frontal Gyrus for Perceptual Go/No-Go Decisions Based on "What," "When," and "Where" Related Information: An fMRI Study. Journal of Cognitive Neuroscience. 2005; 17: 981-993.

fMRI Research Center, Department of Radiology, Center for Neurobiology and Behavior, Columbia University, Neurological Institute, Box B-41, 710 West 168th Street, New York, NY 10032.

Cortical systems engaged during executive and volitional functions receive and integrate input from multiple systems. However, these integration processes are not well understood. In particular, it is not known whether these input pathways converge or remain segregated at the executive levels of cortical information processing. If unilateral information streams are conserved within structures that serve high-level executive functions, then the functional organization within these structures would predictably be similarly organized. If, however, unilateral input information streams are integrated within executive-related structures, then activity patterns will not necessarily reflect lower organizations. In this study, subjects were imaged during the performance of a "perceptual go/no-go" task for which instructions were based on spatial ("where"), temporal ("when"), or object ("what") stimulus features known to engage unilateral processing streams, and the expected hemispheric biases were observed for early processing areas. For example, activity within the inferior and middle occipital gyri, and the middle temporal gyrus, during the what and when tasks, was biased toward the left hemisphere, and toward the right hemisphere during the "where" task. We discover a similar lateralization within the medial frontal gyrus, a region associated with high-level executive functions and decision-related processes. This lateralization was observed regardless of whether the response was executed or imagined, and was demonstrated in multiple sensory modalities. Although active during the go/no-go task, the cingulate gyrus did not show a similar lateralization. These findings further differentiate the organizations and functions of the medial frontal and cingulate executive regions, and suggest that the executive mechanisms operative within the medial frontal gyrus preserve fundamental aspects of input processing streams.

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Anthony H. Risser | | |

Sunday, July 24, 2005

Business World: Takeda's Ramelteon (Rozerem, TAK-375)

From the company's press release:
Takeda Receives Approval from the Food and Drug Administration for ROZEREM™ (ramelteon)

Osaka, Japan, July 23, 2005 - Takeda Pharmaceutical Company Limited (“Takeda”) today announced that its US based global research and development organization, Takeda Global Research & Development Center Inc. has received an approval from the U.S. Food and Drug Administration (FDA) for ROZEREM (ramelteon), 8 mg tablets for the treatment of insomnia. ROZEREM is the first and only prescription sleep medication not designated as a controlled substance by the U.S. Drug Enforcement Administration (DEA). Takeda Pharmaceuticals North America, Inc. will market ROZEREM in the US market.

ROZEREM has a unique therapeutic mechanism of action as compared to existing insomnia treatments because it selectively targets two receptors in the brain's suprachiasmatic nucleus (SCN). The SCN is known as the body's "master clock" because it regulates 24-hour or "circadian" rhythms, including the sleep-wake cycle.

Takeda discovered ramelteon in 1996, and the ROZEREM New Drug Application (NDA), submitted in September 2004, was based on data collected from Takeda’s extensive clinical research program, including recently completed clinical studies with more than 4,200 patients.
[ ... Read the full press release ... ]
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Anthony H. Risser | | |

Thursday, July 21, 2005

Abstract of the Day: Response Shift

Visser MR, Oort FJ, & Sprangers MA. Methods to detect response shift in quality of life data: A convergent validity study. Quality of Life Research. 2005 Apr; 14(3): 629-639.

Department of Medical Psychology, Academic Medical Centre, University of Amsterdam, The Netherlands.

When measuring changes in quality of life (QL) with a pretest-posttest design, response shift can affect results. We investigated the convergent validity of three approaches to detect response shift. (1) In the thentest approach, response shift is measured using a retrospective judgment of pretest QL-levels (thentest). (2) In the anchor-recalibration approach response shift is measured, assessing shifts in patients' individual definitions of the scale-anchors (worst and best imaginable QL) over time. (3) In the Structural Equation Modeling (SEM) approach response shift is indicated by mathematically defined changes in factor solutions and variance-covariance matrices over time. Prior to and three months after invasive surgery, 170 cancer patients completed the SF-36, the Multidimensional Fatigue Inventory (as pre-, post-, and thentest), and the anchor-recalibration task (as pre-, and posttest). Results showed agreement between the thentest and SEM approach on the absence (6 scales) and presence (2 scales) of response shift in 8 of the 9 scales. For the ninth scale both methods detected response shift, but in opposite directions. Possible explanations for this discrepancy are discussed. The anchor-recalibration task agreed with the other approaches on only the absence of response shift in 4 of the 7 scales. The convergent results of thentest and SEM support their validity, especially because they use statistically independent operationalizations of response shift. In this study, recall bias did not invalidate thentest results.

PMID: 16022057 [PubMed - in process]
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Anthony H. Risser | | |

Business World: New Insomnia Meds, Including Takeda's Ramelteon (Rozerem, TAK-375) (cont.)

Forbes.com offers a take on what's happening in the insomnia market:

The Next Ambien?
Matthew Herper
Forbes.com
07.21.05, 6:00 AM ET
Read the article.
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Anthony H. Risser | | |

Wednesday, July 20, 2005

Extremely Low Birth Weight

From The New York Times:
Very Premature Babies Are Still at Risk, Researchers Find
By DENISE GRADY
The New York Times
Published: July 20, 2005

Children born prematurely at weights of 2.2 pounds or less during the 1990's have high rates of mental and physical disability, despite advances in treatment that doctors had hoped would improve their conditions, researchers are reporting today.

Although such infants were much more likely to survive than those born in previous decades - the survival rate was 70 percent in the 1990's, compared with 50 percent in the 1970's and 80's - they were just as likely to suffer from significant disabilities.

Asthma, cerebral palsy, vision and hearing disorders, low I.Q., poor school performance and social difficulties are among the problems described in The Journal of the American Medical Association by doctors at Rainbow Babies and Children's Hospital in Cleveland. Such disabilities were far more common in the children born prematurely than in normal-weight children from similar backgrounds. For example, 38 percent of those born prematurely had I.Q.'s below 85, as opposed to 14 percent of the normal-weight children. Among the premature, 21 percent had asthma, compared with 9 percent of those with normal weight.

"We were astonished by the high number who had at least one of those things," said Dr. Deanne Wilson-Costello, an author of the article in the journal. "The majority had some kind of special need."
[ ... Read the full article ... ]
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Here is the abstract from the JAMA paper:
 
Maureen Hack, MB, ChB; H. Gerry Taylor, PhD; Dennis Drotar, PhD; Mark Schluchter, PhD; Lydia Cartar, MA; Laura Andreias, MD; Deanne Wilson-Costello, MD; & Nancy Klein, PhD. Chronic conditions, functional limitations, and special health care needs of school-aged children born with Extremely Low-Birth-Weight in the 1990s. Journal of the American Medical Association. 2005; 294: 318-325.

Context.  Information on the school-age functioning and special health care needs of extremely low-birth-weight (ELBW, <1000 g) children is necessary to plan for medical and educational services.

Objective.  To examine neurosensory, developmental, and medical conditions together with the associated functional limitations and special health care needs of ELBW children compared with normal-birth-weight (NBW) term-born children (controls).

Design, Setting, and Participants.  A follow-up study at age 8 years of a cohort of 219 ELBW children born 1992 to 1995 (92% of survivors) and 176 NBW controls of similar sociodemographic status conducted in Cleveland, Ohio.

Main Outcome Measures.  Parent Questionnaire for Identifying Children with Chronic Conditions of 12 months or more and categorization of specific medical diagnoses and developmental disabilities based on examination of the children.

Results.  In logistic regression analyses adjusting for sociodemographic status and sex, ELBW children had significantly more chronic conditions than NBW controls, including functional limitations (64% vs 20%, respectively; odds ratio [OR], 8.1; 95% confidence interval [CI], 5.0-13.1; P<.001), compensatory dependency needs (48% vs 23%, respectively; OR, 3.0; 95% CI, 1.9-4.7; P<.001), and services above those routinely required by children (65% vs 27%, respectively; OR, 5.4; 95% CI, 3.4-8.5; P<.001). These differences remained significant when the 36 ELBW children with neurosensory impairments were excluded. Specific diagnoses and disabilities for ELBW vs NBW children included cerebral palsy (14% vs 0%, respectively; P<.001), asthma (21% vs 9%; OR, 3.0; 95% CI, 1.6-5.6; P = .001), vision of less than 20/200 (10% vs 3%; OR, 3.1; 95% CI, 1.2-7.8; P = .02), low IQ of less than 85 (38% vs 14%; OR, 4.5; 95% CI, 2.7-7.7; P<.001), limited academic skills (37% vs 15%; OR, 4.2; 95% CI, 2.5-7.3; P<.001), poor motor skills (47% vs 10%; OR, 7.8; 95% CI, 4.5-13.6; P<.001), and poor adaptive functioning (69% vs 34%; OR, 6.5; 95% CI, 4.0-10.6; P<.001).

Conclusion.  The ELBW survivors in school at age 8 years who were born in the 1990s have considerable long-term health and educational needs.
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Anthony H. Risser | | |

Tuesday, July 19, 2005

Business World: New Insomnia Meds, Including Takeda's Ramelteon (Rozerem, TAK-375)

A brief overview to some of the anticipated insomnia medications trending from this year to next, this is from a recent Reuters report, as published on the International Herald Tribune website:
New entries shake insomnia market's slumber
Reuters
FRIDAY, JULY 15, 2005

LONDON The sleeping pill market, long dominated by Sanofi-Aventis's Ambien, is waking up to a rush of new competition.
 
Improved treatments could double the insomnia market by the end of the decade, but the French company's share of business is set to shrink dramatically, according to industry analysts.
 
The latest challenger is Takeda Pharmaceutical's Rozerem, or ramelteon, which industry sources say could win approval in the crucial U.S. market as early as next week. The expected approval comes hard on the heels of the successful U.S. debut of Sepracor's Lunesta in April.
 
Another two competitors - from two U.S. pharmaceutical companies, Pfizer and Merck - are expected in 2006 and 2008, respectively.
[ ... Read the full report ... ]
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Anthony H. Risser | | |

Abstract of the Day: Neuropsychological Assessment

O'Sullivan M, Morris RG, & Markus HS. Brief cognitive assessment for patients with cerebral small vessel disease. Journal of Neurology, Neurosurgery, and Psychiatry. 2005 Aug; 76(8): 1140-1145.

Division of Clinical Neuroscience, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.

BACKGROUND: Cerebral small vessel disease is a common cause of cognitive impairment and vascular dementia. The cognitive deficit differs from that in Alzheimer's disease, with greater executive/attentional dysfunction and relatively intact episodic memory. OBJECTIVE: To develop brief assessment tools that are better adapted to the neuropsychological profile of cerebral small vessel disease. METHODS: 32 subjects with ischaemic leukoaraiosis (history of lacunar stroke and leukoaraiosis on MRI), aged 50 to 84 years, and 17 age and education matched controls had a brief executive assessment, which took 20 minutes to administer, and a wide range of additional tests. The ability of the brief executive assessment to discriminate between groups-both individually and in combination-was evaluated and compared with that of the whole battery. RESULTS: The brief executive assessment provided good sensitivity and specificity for identifying subjects with ischaemic leukoaraiosis (sensitivity 88%, specificity 88%, using the optimal combination of scores). The best individual tests were trail making and digit symbol, which were both far more sensitive than the mini-mental state examination (MMSE). The ability to discriminate between groups was maintained in subjects with MMSE >27 and across the whole age range. The brief executive assessment performed well compared with the whole battery, with additional tests accounting for only a further 12% of between-group variance. CONCLUSIONS: The brief executive assessment was sensitive to deficits found in ischaemic leukoaraiosis and discriminated them from the cognitive effects of healthy aging. The assessment has potential for bedside use and as a cognitive end point for clinical trials.

PMID: 16024894 [PubMed - as supplied by publisher]
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Anthony H. Risser | | |

Business World: BrainCells, Inc.

A post at Brain Waves (Zack Lynch) outlining news from BrainCells, Inc.
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Anthony H. Risser | | |

Business World: Biogen Idec, Elan, & Tysabri (Natalizumab) and Avonex (Interferon beta-1a)

From: RTE Ireland:
Elan releases Tysabri trial figures

July 19, 2005 11:09

Pharmaceutical  company Elan has released figures showing that its suspended Tysabri drug improved the effectiveness of Biogen's Avonex in the treatment of multiple sclerosis.

'The addition of Tysabri to Avonex resulted in a 24% reduction in the risk of disability progression compared to the effect provided by Avonex alone,' the two companies said. There was also a 56% relative reduction in the rate of clinical relapses.

The companies halted sales of and trials of Tysabri in late February after it was discovered that some patients taking the drug in combination with another treatment had contracted a rare brain disease called PML.

The two firms are currently conducting a safety review before a decision can be made on a possible return of Tysabri to the market. Elan reports its second quarter results on July 28, and may give an update on the progress of the review then.

Shares in Elan were up 28 cent at €6.29 in Dublin by mid-morning.
[ ... Read the full article ... ]
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Read the company press release by clicking here.
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Anthony H. Risser | | |

Saturday, July 16, 2005

Business World: Cyberonics, Neurostimulator (Vagus Nerve Stimulator [VNS]), and Depression

News about this controversial issue (See the list at the bottom of this posting for earlier BrainBlog posts.)

From the company's press release:
FDA APPROVES CYBERONICS’ VNS THERAPY™ SYSTEM FOR TREATMENT-RESISTANT DEPRESSION (TRD)
First FDA-Approved Treatment Specifically for TRD First Implantable Device-Based Treatment for Depression

Conference Call Scheduled for Monday, July 18 at 8:00 AM EDT Investor/Analyst Day at Cyberonics Scheduled for July 25-26


HOUSTON, Texas, July 15, 2005 -- Cyberonics, Inc. (NASDAQ:CYBX) today announced that the United States Food and Drug Administration (FDA) approved the Vagus Nerve Stimulation (VNS) Therapy System “for the adjunctive long-term treatment of chronic or recurrent depression for patients 18 years of age or older who are experiencing a major depressive episode and have not had an adequate response to four or more adequate antidepressant treatments.” VNS Therapy is delivered from a small pacemaker-like generator implanted in the chest that sends preprogrammed, intermittent, mild electrical pulses through the vagus nerve in the neck to the brain. The VNS Therapy System is the first FDA-approved implantable device-based treatment for depression and the first treatment developed, studied, approved and labeled specifically for patients with treatment-resistant depression (TRD). The VNS Therapy System was approved as a treatment for medically refractory epilepsy in Europe in 1994 and in the United States and Canada in 1997 and as a treatment for TRD in Europe and Canada in 2001.
{ ... Read the Full Press Release ... ]
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Previous BrainBlog postings on this topic:

20 May 2005
19 May 2005
07 April 2005
04 February 2005
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Anthony H. Risser | | |

Thursday, July 14, 2005

Abstract of the Day: Dementia

Godbolt AK, Josephs KA, Revesz T, Warrington EK, Lantos P, King A, Fox NC, Al Sarraj S, Holton J, Cipolotti L, Khan MN, & Rossor MN. Sporadic and familial dementia with ubiquitin-positive tau-negative inclusions: Clinical features of one histopathological abnormality underlying frontotemporal lobar degeneration. Archives of Neurology. 2005 Jul; 62(7): 1097-1101.

Author Affiliations: Dementia Research Centre.

BACKGROUND: Frontotemporal lobar degeneration comprises a group of diseases with clinical presentations and underlying histopathologies that overlap. Familial disease occurs in up to 50% of frontotemporal lobar degeneration cases. One of several underlying histopathological abnormalities is of ubiquitin-positive tau-negative inclusions, similar to those in motor neuron disease. OBJECTIVE: To compare clinical features of familial and sporadic cases in this pathological subgroup.Design and Patients Case note review of dementia patients with ubiquitin-positive tau-negative inclusion pathological abnormalities proven by autopsy. SETTING: United Kingdom tertiary referral center. MAIN OUTCOME MEASURES: Analysis of clinical features. RESULTS: Eleven familial cases (autosomal dominant) and 18 sporadic cases were identified. Most familial case patients presented with behavioral disturbances similar to those seen in sporadic behavioral cases. Semantic dementia was only seen in sporadic cases. Atypical features occurred in a minority. Sporadic and familial behavioral cases showed no differences in age at onset or disease duration. Neuropsychological test results revealed frontal or temporal deficits in most, but unexpected early parietal deficits in 1. CONCLUSIONS: Behavioral features in familial and sporadic cases were similar, but semantic dementia only occurred in sporadic cases. Diagnostic confusion with Alzheimer disease and corticobasal degeneration occurred in some cases.

PMID: 16009765 [PubMed - in process]
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Anthony H. Risser | | |

Upcoming Event: Athens, 17-20 September 2005

The 9th Congress of the European Federation of Neurological Societies (EFNS) will be held in Athens, Greece, from the 17th through the 20th of September, 2005.

The conference includes a special session on the topics of Neurology and Art and Sequels of cerebral lesions in artists: Reflections on the neurology of creativity, organized by Drs. Julien Bogousslavsky of Lausanne, Switzerland and François Boller of Paris, France.

Information about the conference can be found at the EFNS 2005 webpage.
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Anthony H. Risser | | |

Wednesday, July 13, 2005

Upcoming Event: Bethesda, 19 September 2005

Dr. Lizabeth Romanski presents Encoding and integration of communication signals by the primate prefrontal cortex as part of the 2005-2006 NIH Neuroscience Seminar Series. 12 Noon, Building 10's Lipsett Amphitheater on the campus of the National Institutes of Health (NIH) in Bethesda, MD.
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Anthony H. Risser | | |

Cognition-Enhancer Pharmaceuticals: Foresight Report

Here is the Executive Summary of the newly released Foresight report on cognition enhancers:
Executive Summary

"The search for treatments for dementia, alongside other scientific and societal changes, has prompted the development of symptomatic treatments and disease-modifying drugs for people with degenerative brain diseases, mild cognitive impairment, and psychiatric diseases that involve cognition impairment. The enhancement of aspects of cognition, such as learning and memory, now seems possible for people with normal age-related decline and in healthy people, although so far the effects of these cognition enhancers are modest. The next two decades are likely to bring deeper knowledge of the mechanisms of learning, memory, and forgetting, together with an understanding of the relationship between changes in molecules, cells and brain circuits, and changes in cognition. Already, research efforts by the pharmaceutical industry are poised to deliver many more disease modifiers and putative cognition enhancers, though limitations exist in translating laboratory findings into effective interventions for human use.

"If effective interventions become available, their general use will bring health, social, ethical and regulatory issues. The widespread use of cognition enhancers for healthy people could have substantial impact and potentially become problematic – a minority may have abuse liability. Mechanisms do not exist currently to regulate cognition enhancers for non-medical purposes, though social changes together with commercial pressures mean that their use for enhancement is likely to be increasingly required, desired and accepted. Their use for disease-related impairments seems unlikely to cause concerns if cost-effective treatments are used to enhance function and quality of life. New challenges will include the development of biomarkers to allow early intervention and the targeting of therapies for the best effect on the individual."
The full report can be accessed at Cognition Enhancers.
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Anthony H. Risser | | |

Cognition-Enhancer Pharmaceuticals

A new report, from Britain, on trends and future possibilities for cognitive-enhancing medications (sometimes referred to as "cosmetic neurology, " "nootropics," and "smart drugs") has been released.

From the BBC:
Brain-boost drugs 'to be common'

Healthy people, including children, might one day take drugs to boost their intelligence, scientists predict.

The think-tank Foresight, outlined the scenario in an independent report looking at potential developments over the next 20 years.

Such "cognitive enhancers" could become as "common as coffee", they suggest.

Scientists did not rule out children taking exams facing drug tests, as sportsmen do, to see if any have taken 'performance enhancing substances'.

The report was compiled by 50 experts, who set out their predictions for the next two decades.
[ ... Read the full article ... ]
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You can download the 44-page Foresights report by accessing this link: Cognition enhancers by Roy Jones, Kelly Morris, and David Nutt.
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Anthony H. Risser | | |

Upcoming Event: Philadelphia, 11 November 2005

A conference on the topic of frontotemporal dementia (FTD), directed toward caregivers, will be held on the campus of the University of Pennsylvania on the 11th of November, 2005.

From the conference's webpage:
"In this day-long Caregiver Conference, experts in the field of FTD will review medical causes and treatments; individual management of patient needs from nursing, social work, and physical/occupational therapy perspectives; family counseling; and disease management.  Dr. Daniel Gottlieb ... will be the keynote speaker. Break-out groups following each session will provide opportunity for discussion. 

There is no charge to attend this event, but space is limited so you must register before October 15, 2005".

For more information, please visit the meeting's webpage.
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Anthony H. Risser | | |

Boundary Extension at Cognitive Daily

Dr. David Munger posts an interesting presentation about Boundary Extension and Emotion at his and Dr. Greta Munger's Cognitive Daily blog.

In addition to providing an example of this phenomenon of memory functioning, he discusses a recent study by Drs. Andrew Mathews and Bundy Mackintosh of the MRC Cognition and Brain Sciences Unit of Cambridge University.
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Here's the abstract of a Mathews and Mackintosh study:

Mathews A, Mackintosh B. Take a closer look: Emotion modifies the boundary extension effect. Emotion. 2004 Mar; 4(1): 36-45.

MRC Cognition and Brain Sciences Unit, Cambridge, England.

Evidence has accumulated showing that central aspects of negative emotional scenes are remembered better than equivalent aspects of nonemotional scenes. Previous work, and an attentional account of these findings, led the authors to predict that anxiety-prone individuals would remember extremely negative emotional pictures as if seen from a closer perspective (i.e., with a less extended background) than other pictures. Findings showed that boundary extension was indeed reduced in high-trait-anxious individuals for very negative scenes, and this was more generally true for arousing scenes, with the exception of those with positive content. These findings are taken to be support for the view that attending to central aspects of emotionally arousing scenes can restrict the usual extended impression of surrounding space.

PMID: 15053725 [PubMed - indexed for MEDLINE]
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Anthony H. Risser | | |

Monday, July 11, 2005

Musical Hallucinations

From tomorrow's New York Times:
Neuron Network Goes Awry, and Brain Becomes an IPod
By CARL ZIMMER
The New York Times
Published: July 12, 2005

[snip]

Only a handful of brain scans have been made of people with musical hallucinations. Dr. Tim Griffiths, a neurologist at the University of Newcastle Upon Tyne in England, performed one of these studies on six elderly patients who developed musical hallucinations after becoming partly deaf.

Dr. Griffiths used a scanning technique known as PET, which involves injecting radioactive markers into the bloodstream. Each time he scanned his subjects' brains, he asked them whether they had experienced musical hallucinations. If they had, he asked them to rate the intensity on a scale from one to seven.

Dr. Griffiths discovered a network of regions in the brain that became more active as the hallucinations became more intense. "What strikes me is that you see a very similar pattern in normal people who are listening to music," he said.

The main difference is that musical hallucinations don't activate the primary auditory cortex, the first stop for sound in the brain. When Dr. Griffith's subjects hallucinated, they used only the parts of the brain that are responsible for turning simple sounds into complex music.

These music-processing regions may be continually looking for signals in the brain that they can interpret, Dr. Griffiths suggested. When no sound is coming from the ears, the brain may still generate occasional, random impulses that the music-processing regions interpret as sound. They then try to match these impulses to memories of music, turning a few notes into a familiar melody.

[snip]
[ ... Read the full article ...]
~
Visit Carl Zimmer’s blog: The Loom
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Anthony H. Risser | | |

Business World: Takeda's Ramelteon (TAK-375)

A Reuters report:
Takeda may extend sleeping pill's use for Alzheimer's
Mon Jul 11, 2005 05:41 AM ET
TOKYO, July 11 (Reuters) - Japan's biggest drug maker, Takeda Pharmaceutical Co. Ltd ... said on Monday it is on track to release a sleeping pill as early as September in the United States and may extend its use to treat Alzheimer's disease and other illnesses.

The Osaka-based drug maker plans to launch its insomnia drug Ramelteon in the U.S. market in September or October, marking its entry into the central nervous system disease segment, Takeda President Yasuchika Hasegawa told an analysts' meeting.
[ ... Read the full report ...]
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Anthony H. Risser | | |

Neuroscience-of-Orgasm Studies and The Secret Life of the Brain; Dementia, too

The Mind Hacks blog crew posted two posts today that provide links to an Australian radio show’s detailed look at recent neuroscientific studies of orgasm and to content and visual segments from the PBS series The Secret Life of the Brain which aired several years back, but remains available online. I recall that the PBS show's website had pretty decent rotatable 3-D brain graphics which my undergraduate course at that time reported enjoying:

Mind Hacks on All in the Mind on the 'orgasmic brain'.

Mind Hacks on The Secret Life of the Brain on PBS.

Thanks, Mind Hacks!

(Note: Looking the All in the Mind webpage on the Australian Broadcasting Corporation (ABC) website indicates that the two prior shows by that radio host were on the topic of dementia. As with the neuroscience-of-orgasm show, these dementia shows have available media streams and transcripts.)
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Anthony H. Risser | | |

Sunday, July 10, 2005

Williams Syndrome: fMRI Study of Social Cognition

From the BBC
‘Over-friendly' brain clues found

Scientists have uncovered clues about what happens in the brain to make some people "over-friendly".

US National Institute of Mental Health experts looked at differences in the brains of people with an abnormality which makes them highly sociable.

Researchers used scans to identify areas which failed to work properly when they saw frightening faces.

In Nature Neuroscience, they say this could give clues for understanding social disorders in others.

Scary faces

People with the genetic condition Williams Syndrome lack around 21 genes on chromosome seven.

Their lack of fear means they will impulsively engage in social situations, even with strangers.

But they often have heightened anxiety about non-human fears, such as spiders or heights.
[ ... Read the full report ... ]
~
Here is the study's abstract:

Andreas Meyer-Lindenberg, Ahmad R Hariri, Karen E Munoz, Carolyn B Mervis, Venkata S Mattay, Colleen A Morris, & Karen Faith Berman. Neural correlates of genetically abnormal social cognition in Williams syndrome. Nature Neuroscience Published online: 10 July 2005; [ doi:10.1038/nn1494 ].

Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

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Anthony H. Risser | | |

Saturday, July 09, 2005

Dr. Michael Gazzaniga on C-SPAN's BookTV

A mid-June interview of Dr. Michael Gazzaniga by novelist Tom Wolfe is airing this weekend on C-SPAN's BookTV. Topics include neuroethics and Gazzaniga's newest book, The Ethical Brain. The interview was held at the New York Academy of Sciences.

See the C-SPAN website for air times.
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Anthony H. Risser | |

Upcoming Event: Montreal, 14-17 July 2005

The annual meeting of the Canadian Society for Brain, Behaviour and Cognitive Science (CSBBCS)/La Société canadienne des sciences du cerveau, du comportement et de la cognition (SCSCCC) will be held at Université de Montréal.

From the website:
"The Canadian Society for Brain, Behaviour and Cognitive Science (CSBBCS) is a non-profit organization whose primary function is to advance Canadian research in experimental psychology and behavioral neuroscience. Each year the society holds an annual meeting that includes paper sessions, symposia, posters, a distinguished lecture, business meeting and lots of high quality scientific interaction.

"La Société canadienne des sciences du cerveau, du comportement et de la cognition (SCSCCC) est une organisation à but non lucratif, dont la principale raison d'être est de faire avancer la recherche canadienne sur la psychologie expérimentale et la neuroscience comportementale. Chaque année la société organise une réunion annuelle qui inclut des sessions avec présentations orales et par affiches, des symposiums, une conférence par une personne éminente, une réunion d'affaires et beaucoup d'interactions scientifiques de haut niveau.

One highlight of the conference is a talk by Dr. Doreen Kimura, recipient of the society's Hebb Award. The title of Dr. Kimura's talk is "Recollections of an accidental contrarian."

Details about the meeting can be found on the conference website
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Anthony H. Risser | | |

Essential Tremor: Treatment Practice Parameters

The American Academy of Neurology (AAN) has produced a practice parameter about therapies for essential tremor. The full-text of the paper in available online at the academy's Neurology journal website:

T. A. Zesiewicz, MD, R. Elble, MD, PhD, FAAN, E. D. Louis, MD, MS, FAAN, R. A. Hauser, MD, MBA, FAAN, K. L. Sullivan, MSPH, R. B. Dewey, Jr, MD, FAAN, W. G. Ondo, MD, G. S. Gronseth, MD, and W. J. Weiner, MD, FAAN. Practice parameter: Therapies for essential tremor; Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2005; 64: 2008-2020.

[ ... Read the full article ... ]
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Anthony H. Risser | | |

Friday, July 08, 2005

Genetics and Aggressive Behavior in a Mouse Model

From The Globe and Mail:
Rampaging mice made more human
By CAROLYN ABRAHAM
Wednesday, July 6, 2005 Updated at 8:57 AM EDT
From Wednesday's Globe and Mail

A breakthrough experiment has used a human gene to turn vicious mice into very gentle creatures -- holding out the prospect of doing similarly sweet things to violent people.

Scientists at the University of British Columbia's Centre for Molecular Medicine and Therapeutics created a strain of extremely vicious lab mice three years ago after accidentally deleting a gene that affects brain development.

The mutant mice were so aggressive they killed their mates, chewed their siblings' tails and even attacked their lab handlers.

The unanswered question was whether the human form of the gene also plays a role in aggression in people. The new research now suggests that it does.

By giving mutant mice embryos the human version of the gene they were missing, the UBC team found the nasty rodents grew into a rather nice strain instead.

As such, the experiment raises the possibility of designing a gene therapy to counter aggression -- as well as the eerie spectre of enhancing it.

More immediately, it means mice can act as models to study human genes involved in abnormal behaviour and psychiatric disorders.
[ ... Read the full article ... ]
~

From the UBC press release:
Human Gene Corrects Pathological Aggression in Mice
Mouse model opens new door to testing genetic causes of mental illnesses

VANCOUVER, BC – July 6th, 2005: Dr. Elizabeth M. Simpson, a CMMT investigator at the BC Research Institute, provides the first example of a human gene correcting aggressive mouse behaviour and suggests that genetic mechanisms underlying the ‘fierce’ mouse may be similar to those found in humans.

Published today in the Journal for Neuroscience, Dr. Elizabeth M. Simpson demonstrated that a human brain gene (NR2E1) can prevent abnormal brain development and aggressive behaviour in mice. This work establishes a system to functionally evaluate the role of human genes in psychiatric disease.

“We now have developed a powerful paradigm that scientists can use to test, in an animal model, human genes that may be implicated in abnormal behaviour and psychiatric diseases,” says Dr. Simpson, a Canada Research Chair in Genetics and Behaviour.

Dr. Simpson uses mouse models to understand the genetic components of mental illness. In 2002, Dr. Simpson and others demonstrated that mice lacking both copies of the critical Nr2e1 gene had abnormal brain development and extreme aggressive behaviour. These mice were dubbed the ‘fierce’ mice. This earlier discovery was significant because it showed that a single gene deletion in mice could produce an extreme behaviour, regardless of environment, and in a predictable inheritance pattern.

“Our results now show that the human NR2E1 gene can replace the mouse gene resulting in a mouse with normal brain development and non aggressive behaviour. This work provides further support for the use of mouse as a model for human disease, especially in the challenging field of human brain disorders and psychiatric illness”, said Dr. Simpson. “As already seen with diabetes and cystic fibrosis, such mouse models could have significant implications for the development of new therapeutic targets for human brain disorders.“

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Anthony H. Risser | | |

Upcoming Event: Los Angeles, 31 July - 03 August 2005

From the University of Southern California website:

US-Japan Conference on Drug Development and Rational Drug Design - Pathways of Innovative Drug Targeting: From a Molecular to Clinical Perspective

This conference represents the 3rd Conference on Drug Development and Rational Drug Design to be held between the USC School of Pharmacy and its affiliated schools of pharmacy in Japan.
Location: Hilton Los Angeles/ Universal City
Contact Info: (323) 442-2403 or pharmce@usc.edu

Sponsored by USC School of Pharmacy, Kyoto University, Meijo University, Nagoya City University. Tokyo University of Pharmaceutical and Life Science, Toyama Medical and Pharmaceutical University, The University of Tokyo.
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Anthony H. Risser | | |

Thursday, July 07, 2005

Falls in the Elderly

Cognitive factors may increase the probability of falls in the elderly. As well, falls are a preventable cause of head and brain trauma. Therefore, the topic is always of concern to clinical neuroscientists who work with older individuals.

Available in full-text format, including a fact sheet for patients:

Shobha S. Rao. Prevention of Falls in Older Patients. American Family Physician 2005; 72: 81-8 & 93-4.

University of Texas Southwestern, Dallas, Texas

Abstract:

Falls are one of the most common geriatric syndromes threatening the independence of older persons. Between 30 and 40 percent of community-dwelling adults older than 65 years fall each year, and the rates are higher for nursing home residents. Falls are associated with increased morbidity, mortality, and nursing home placement. Most falls have multiple causes. Risk factors for falls include muscle weakness, a history of falls, use of four or more prescription medications, use of an assistive device, arthritis, depression, age older than 80 years, and impairments in gait, balance, cognition, vision, and activities of daily living. Physicians caring for older patients should ask about any falls that have occurred in the past year. Assessment should include evaluating the circumstances of the fall and a complete history and physical examination, looking for potential risk factors. The most effective fall prevention strategies are multifactorial interventions targeting identified risk factors, exercises for muscle strengthening combined with balance training, and withdrawal of psychotropic medication. Home hazard assessment and modification by a health professional also is helpful.

[ ... Read the full article ... ]
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Anthony H. Risser | | |

Wednesday, July 06, 2005

Business World: Neurochem's Alzhemed and Alzheimer Disease

Neurochem completes patient recruitment for North American Phase III clinical trial for Alzhemed(TM)
Milestone on Schedule
Tuesday July 5, 8:31 am ET

LAVAL, QC, July 5 /PRNewswire-FirstCall/ - Neurochem Inc. ... announced today the completion of recruitment of the 950 patients with mild-to- moderate Alzheimer's Disease (AD) for its North American Phase III clinical trial for Alzhemed(TM), the Company's investigational product candidate for the treatment of AD. The trial is being conducted in 51 U.S. and 17 Canadian clinical centers across North America. The Company has completed the selection of sites for a similarly sized Phase III clinical trial in Europe and expects to begin patient recruitment in the fall of 2005.

[ ... Read the full press release ... ]

From the Neurochem website:
"About Alzhemed™
Alzhemed™ is an orally administered, small organic molecule that has been specifically designed to modify the course of AD through its anti-amyloid activity. As part of a "disease modifying" novel class of product candidates, Alzhemed™ is expected to act at two levels: in preventing and stopping the formation and the deposition of amyloid fibrils in the brain and in binding to soluble A[beta] protein to reduce the amyloid-induced toxicity on neuronal and brain inflammatory cells associated with amyloid build-up in AD."

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Anthony H. Risser
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Tuesday, July 05, 2005

Coma Dissipation

From The Boston Globe:

After a coma
Comebacks are slow and patchy, and almost never miraculous
By Carey Goldberg
The Boston Globe
July 5, 2005

[ ... Read the article ... ]
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Anthony H. Risser | | |

Specialized Neurons of the Medial Temporal Lobe

This study has been reported in the media in a number of different locations. Today, The New York Times includes a small report about it:
A Neuron With Halle Berry's Name on It
By SANDRA BLAKESLEE
The New York Times
Published: July 5, 2005

Scientists have long wondered whether the brain contains "grandmother" cells - one or a few neurons that fire in response to the familiar face of your grandmother. A new study suggests that the answer may be yes.

And it is not just Grandma.

If you are a Halle Berry fan, you have a Halle Berry cell or two in your brain. Not a region, but a single cell or a small handful that fire in response to her face in various angles and poses, her body in a cat suit, the string of letters in her name and other distinct features of the actress who plays Cat Woman.

Dr. Christof Koch, a neuroscientist at the California Institute of Technology who helped conduct the study, said some neuroscientists had long argued for specialized neurons.

Others have said the brain does not have enough neurons to be that specialized, Dr. Koch said.

[ ... Read the full article ... ]

Here is the abstract of the study, published in the journal Nature:

Quiroga RQ, Reddy L, Kreiman G, Koch C, &Fried I. Invariant visual representation by single neurons in the human brain. Nature. 2005 Jun 23; 435(7045): 1102-1107.

Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA.

It takes a fraction of a second to recognize a person or an object even when seen under strikingly different conditions. How such a robust, high-level representation is achieved by neurons in the human brain is still unclear. In monkeys, neurons in the upper stages of the ventral visual pathway respond to complex images such as faces and objects and show some degree of invariance to metric properties such as the stimulus size, position and viewing angle. We have previously shown that neurons in the human medial temporal lobe (MTL) fire selectively to images of faces, animals, objects or scenes. Here we report on a remarkable subset of MTL neurons that are selectively activated by strikingly different pictures of given individuals, landmarks or objects and in some cases even by letter strings with their names. These results suggest an invariant, sparse and explicit code, which might be important in the transformation of complex visual percepts into long-term and more abstract memories.

PMID: 15973409 [PubMed - in process]
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Anthony H. Risser | | |

Friday, July 01, 2005

Amgen's GDNF and Parkinson Disease

From the AP, via The WashingtonPost.com website, concerning glial cell line-derived neurotrophic factor (GDNF):
Autopsy Shows Parkinson's Drug's Progress
By RANDOLPH E. SCHMID
The Associated Press
Friday, July 1, 2005; 3:57 PM

WASHINGTON -- A drug withdrawn from clinical trials because of safety concerns was helping regrow nerve fibers in the brain of a man with Parkinson's disease, scientists report.

The finding probably will renew debate over the drug, GDNF. It had offered encouragement to people with Parkinson's who reported improvement when using it in trials. But the drug was withdrawn by the manufacturer, Amgen, this year.

Some of those patients in the trial sued Amgen to get continued supplies of the drug. They were turned down by a federal judge in New York in June. A second suit is pending.

Seth Love, Steven S. Gill and colleagues at Frenchay Hospital in Bristol, England, report in Monday's issue of the journal Nature Medicine that an autopsy of the brain of one of the patients who received the drug in an early trial shows that nerve fibers that are lost in the disease were growing back.
[ ... Read the full article ... ]
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Anthony H. Risser
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