Thursday, June 30, 2005

Functional Magentic Resonance Imaging (fMRI) Online Educational Resources

For individuals wishing to learn about functional magnetic resonance imaging (fMRI), two great online resources come to mind.

The first is an excellent collection of PowerPoint lectures by Dr. Jody Culham of the University of Western Ontario, available on her website fMRI For Dummies. These lectures are extraordinarily well organized.

The second is another excellent collection - of multimedia streams (for Windows and Mac): Dr. Geoffrey Aguirre's fMRI Course, November 2004 from the University of Pennsylvania.
Anthony H. Risser | | |

Abstract of the Day: Aphasia

Hengst JA, Frame SR, Neuman-Stritzel T, & Gannaway R. Using others' words: Conversational use of reported speech by individuals with aphasia and their communication partners. Journal of Speech, Language, and Hearing Research. 2005 Feb; 48(1): 137-156.

Department of Speech and Hearing Science, University of Illinois at Urbana-Champaign, 61820, USA.

Reported speech, wherein one quotes or paraphrases the speech of another, has been studied extensively as a set of linguistic and discourse practices. Researchers agree that reported speech is pervasive, found across languages, and used in diverse contexts. However, to date, there have been no studies of the use of reported speech among individuals with aphasia. Grounded in an interactional sociolinguistic perspective, the study presented here documents and analyzes the use of reported speech by 7 adults with mild to moderately severe aphasia and their routine communication partners. Each of the 7 pairs was videotaped in 4 everyday activities at home or around the community, yielding over 27 hr of conversational interaction for analysis. A coding scheme was developed that identified 5 types of explicitly marked reported speech: direct, indirect, projected, indexed, and undecided. Analysis of the data documented reported speech as a common discourse practice used successfully by the individuals with aphasia and their communication partners. All participants produced reported speech at least once, and across all observations the target pairs produced 400 reported speech episodes (RSEs), 149 by individuals with aphasia and 251 by their communication partners. For all participants, direct and indirect forms were the most prevalent (70% of RSEs). Situated discourse analysis of specific episodes of reported speech used by 3 of the pairs provides detailed portraits of the diverse interactional, referential, social, and discourse functions of reported speech and explores ways that the pairs used reported speech to successfully frame talk despite their ongoing management of aphasia.

PMID: 15934449 [PubMed - in process]
Anthony H. Risser
| | |

Tuesday, June 28, 2005

Shelby Foote, Deceased

To celebrate the career of Shelby Foote, 88-year-old novelist and Civil War historian, who died last night, here's an abstract about head injuries during the Civil War:

Kaufman HH. Treatment of head injuries in the American Civil War. Journal of Neurosurgery. 1993 May; 78(5): 838-845.

Department of Neurosurgery, West Virginia University School of Medicine, Morgantown.

At the time of the American Civil War (1861-1865), a great deal was known about closed head injury and gunshot wounds to the head. Compression was differentiated from concussion, but localization of lesions was not precise. Ether and especially chloroform were used to provide anesthesia. Failure to understand how to prevent infection discouraged physicians from aggressive surgery. Manuals written to educate inexperienced doctors at the onset of the war provide an overview of the advice given by senior surgeons. The Union experiences in the treatment of head injury in the Civil War were discussed in the three surgical volumes of The Medical and Surgical History of the War of the Rebellion. Wounds were divided into incised and puncture wounds, blunt injuries, and gunshot wounds, which were analyzed separately. Because the patients were not stratified by severity of injury and because there was no neuroimaging, it is difficult to understand the clinical problems and the effectiveness of surgery. Almost immediately after the war, increased knowledge about cerebral localization and the development of antisepsis (and then asepsis) permitted the development of modern neurosurgery.

Publication Types: Historical Article

PMID: 8468618 [PubMed - indexed for MEDLINE]
Anthony H. Risser | | |

Sunday, June 26, 2005

Business World: Acadia Pharm, ACP-103, & Parkinson Disease

From an AP report posted at Yahoo!:

Acadia Pharma Says Drug Study Encouraging
Wednesday June 22, 7:44 pm ET

Acadia Pharmaceuticals Says Lead Drug Helped Psychosis in Parkinson's Patients; Shares Fall

SAN DIEGO (AP) -- Acadia Pharmaceuticals Inc. on Wednesday said an ongoing mid-stage trial showed that its experimental drug did a better job than a placebo in reducing hallucinations and delusions in Parkinson's disease patients who suffer treatment-induced psychosis.


Acadia said patients taking ACP-103 -- its lead drug candidate -- showed a greater reduction in psychotic symptoms than those taking a placebo, particularly lower hallucinations and delusions. The study involves 60 patients and the interim data came from an analysis of the first 30 patients to complete the trial. Acadia said no serious side effects were reported from ACP-103.

[ ... Read the full article ... ]
From the Acadia website:
" ACP-103, a proprietary small molecule discovered by ACADIA, is in development for treatment of the psychiatric and motoric dysfunction that frequently results from current Parkinson's disease therapies. ACP-103 is given orally and blocks the activity of the 5-HT2A receptor, a drug target that plays an important role in the treatment of various neuropsychiatric disorders."
Anthony H. Risser | | |

Saturday, June 25, 2005

Upcoming Event: Princeton, 15 October 2005

On the 15th of October 2005, a meeting will be held on the campus of Princeton University: Cognitive Neuroscience at Penn and Princeton: Graduate Student Symposium. Refer to the meeting webpage [click here] for additional information.
Anthony H. Risser | | |

Sensory Modelling

From The Los Angeles Times:
Cricket 'Hearing' Sense Copied in Lab
By Alex Raksin
The Los Angeles Times
25 June 2005

Crickets are famous for making a racket disproportionate to their size. What has drawn many biologists to them, however, is their "hearing" — or more precisely, how they use cerci, super-sensitive hairs on their back, to pinpoint minute shifts in air currents, such as the waft of an attacking wasp or spider.

Now, a team of physicists has recreated an admittedly crude facsimile of the insects' efficient sensory system in the lab.

Attaching a few hundred thin plastic wires to sockets on silicon wafer sheets, the researchers developed "a prototype for technologies, such as hearing aids and sensors, that could help aerospace engineers visualize how air currents move across wings," said Gijs Krijnen, a physicist who led the project with colleague Remco Wiegerink at the University of Twente in the Netherlands.

They describe their work in the current issue of the Journal of Micromechanics and Microengineering.

Like the crickets' cerci, the wires are up to 1 millimeter long and are capable of rotating in response to air currents. That movement creates a tiny electrical impulse that is fed through the socket to a central computer.

Krijnen concedes that his team has yet to figure out how cricket neural networks are able to correlate data from cerci in time to help the insects hop safely away from predators. Thus, the physicists cannot mimic that process in their artificial system.

Still, Krijnen said, his device is already a viable prototype. "It can measure air pressure and particle velocity with much more precision and sensitivity" than existing technologies, he said.

Krijnen's team created the artificial cricket hairs as part of CICADA, a European Union project aimed developing a life-like perception system.

Anthony H. Risser | | |

Transient Ischemic Attack (TIA)

From the BBC:
Test 'identifies new stroke risk'

Doctors have developed a simple checklist to show if patients who have had a mini-stroke are at immediate risk of a more serious attack.

The Oxford University team, writing in the Lancet, said it could help identify those needing emergency treatment.

It looks at age, blood pressure, symptoms and how long the mini-stroke, or transient ischemic attack, lasted.

UK guidelines say all such patients should be checked within seven days, but many wait at least two weeks.

The researchers say their guide could be used to help identify the 10% of patients who are at risk of having a major stroke within seven days of a mini-stroke.

Giving this group blood-thinning drugs or other treatments to reduce their blood pressure or cholesterol can cut their risk of further attacks.
[ ... Read the full article ... ]
The study was headed by Dr. Peter Rothwell.
Anthony H. Risser | | |

Friday, June 24, 2005

ADHD Treatment

The full-text contents of the following article is available on the Pediatrics website at this link [Click here]:

Ronald T. Brown, Robert W. Amler, Wendy S. Freeman, James M. Perrin, Martin T. Stein, Heidi M. Feldman, Karen Pierce, Mark L. Wolraich and the Committee on Quality Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder. Treatment of Attention-Deficit/Hyperactivity Disorder: Overview of the evidence. Pediatrics 2005; 115: e749-e757.

Snipped from the Abstract:
"The evidence strongly supports the use of stimulant medications for treating the core symptoms of children with ADHD and, to a lesser degree, for improving functioning. Behavior therapy alone has only limited effect on symptoms or functioning of children with ADHD, although combining behavior therapy with medication seems to improve functioning and may decrease the amount of (stimulant) medication needed. Comparison among stimulants (mainly methylphenidate and amphetamines) did not indicate that 1 class outperformed the other."

Anthony H. Risser | | |

Abstract of the Day: Alzheimer Disease

Pignatti R, Rabuffetti M, Imbornone E, Mantovani F, Alberoni M, Farina E, & Canal N. Specific impairments of selective attention in mild Alzheimer's disease. Journal of Clinical and Experimental Neuropsychology. 2005 May; 27(4): 436-448.

Neurorehabilitation Unit, Universita di Milano, Fondazione Don Carlo Gnocchi IRCCS, Milan, Italy.

The aim of the present study was to evaluate selective visual attention in subjects affected by Alzheimer's Disease (AD), by means of a computerized spatial exploration test that adopts a Touch Screen (TS) interface, which has already proved able to characterize alternative strategies in performing search tasks. We assessed a group of 16 patients affected by mild to moderate AD, comparing them with 16 control subjects matched for age and education. In the experimental tasks the performance of the AD patients was worse than that of the normal elderly, both quantitatively (slower speeds) and qualitatively (poorer planning and higher number of omissions and perseverations). In the visual attention tasks there appeared to be no close connection between AD patients' performance and increased Reaction Times (RT); this evidenced a specific role of non-elementary cognitive structures enclosed in a higher attentional domain, rather than a general decrease in the speed of basic cognitive processes. Our results are in line with specific AD literature: while psychomotor speed and lower attention levels (sensorimotor) are preferentially impaired in subcortical forms of dementia, the higher levels of selective and divided attention could be the first to deteriorate and appear more markedly disrupted in the Alzheimer type of dementia.

PMID: 15962690 [PubMed - in process]
Anthony H. Risser
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Thursday, June 23, 2005

Abstract of the Day: Text-Comprehension Deficits

Ferstl EC, Walther K, Guthke T, & von Cramon DY. Assessment of story comprehension deficits after brain damage. Journal of Clinical and Experimental Neuropsychology. 2005 Apr; 27(3): 367-384.

Day Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany.

A story comprehension task was specifically developed for the clinical diagnosis of text comprehension deficits. The performance of 49 healthy control participants on qualitatively different Yes/No questions confirmed that both salience and explicitness of information had an impact on question difficulty. An unselected group of brain damaged patients (n = 96) made more errors, particularly on questions about implicit information. The subgroup of patients with left-hemispheric vascular aetiology (n = 18) had particular difficulties with stated details, patients with right-hemispheric vascular aetiology (n = 12) with implicit main ideas, and patients with traumatic brain injury (n = 34) were most impaired on implicit information. Correlations with neuropsychological test scores also confirmed that the questions successfully tapped different subprocesses of comprehension. Performance on implicit main ideas was correlated with tests of executive functions, whereas the performance on the other three question types was correlated with long-term memory and verbal learning. These results suggest that the story comprehension test is a useful diagnostic tool for neuropsychological assessment.

PMID: 15969358 [PubMed - in process]
Anthony H. Risser | | |

Upcoming Event: Boston, 20-21 September 2005

A conference on ion channels in disease biology and ion channel targets in drug discovery will be held in Waltham (Boston region), Massachusetts on the 20th and 21st of September 2005. Further information about the meeting can be found at the following webpage: Click here.
Anthony H. Risser | | |

Tuesday, June 21, 2005

Antipsychotic Medications

The new issue of the Canadian Medical Association Journal includes a review article of modern and older antipsychotic medications. The article is available in free, full-content format.

David M. Gardner, Ross J. Baldessarini, and Paul Waraich. Modern antipsychotic drugs: A critical overview. Canadian Medical Association Journal 2005; 72(13): 1703.


CONVENTIONAL ANTIPSYCHOTIC DRUGS, used for a half century to treat a range of major psychiatric disorders, are being replaced in clinical practice by modern "atypical" antipsychotics, including aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone among others. As a class, the newer drugs have been promoted as being broadly clinically superior, but the evidence for this is problematic. In this brief critical overview, we consider the pharmacology, therapeutic effectiveness, tolerability, adverse effects and costs of individual modern agents versus older antipsychotic drugs. Because of typically minor differences between agents in clinical effectiveness and tolerability, and because of growing concerns about potential adverse long-term health consequences of some modern agents, it is reasonable to consider both older and newer drugs for clinical use, and it is important to inform patients of relative benefits, risks and costs of specific choices.
Anthony H. Risser | | |

Sunday, June 19, 2005

Upcoming Event: Dublin, 06-09 July 2005

The International Neuropsychological Society (INS) Summer Meeting will take place in Dublin, from the 6th of July through the 9th of July 2005. This year's meeting is a joint meeting with the British Neuropsychological Society (BNS) and the Division of Neuropsychology of the British Psychological Society. The location is the Burlington Hotel. Information about the conference can be found at the meeting webpage.

This year's INS Presidential Address is by Dr. Robert Heaton and is entitled Ecological Validity of Neuropsychological Tests versus Analog Measures of Everyday Functioning.
Anthony H. Risser | | |

Thursday, June 16, 2005

Art: The Nervous System as Art Exhibit

Neuroscapes 2006 has put out a call for submissions for what will become an art exhibition. Details are provided at the project's website.

From the website:
"This exhibition will be the first public display of the world best images captured within the brain by neuroscientists using a spectrum of state-of-the-art technologies.

The exhibition is in honor of 100 years since Santiago Ramón y Cajal was jointly awarded the Nobel Prize with Camillo Golgi for their work on revealing the structure of the Brain.

The exhibition is part of the continuing effort by the CosmoCaixa, Barcelona Science Museum of La Caixa Foundation, International Brain Research Organization (IBRO, and Spanish Council for Scientific Research (CSIC, to provide quality artistic and educational resources related to Neurosciences.

The exhibition will contain 50 of the world's most artistic images that capture landmark concepts of how the brain works. In addition, virtual reality, computer presentations and animations are also considered to accompany the exhibition. The exhibition will open at the Barcelona Science Museum in the spring of 2006."
According to the website, the deadline for submissions is 30 November 2005.

There are three topic areas: scientific images of the nervous system, interpreted images of the nervous system (i.e., "images modified ... in order to expound an idea"), and "the cyberbrain" (i.e., virtual reality computer presentations).
Anthony H. Risser | | | |

Abstract of the Day: Executive Task Performance and Functional Status in Elderly Persons

Rapp MA, Schnaider Beeri M, Schmeidler J, Sano M, Silverman JM, Haroutunian V. Relationship of neuropsychological performance to functional status in nursing home residents and community-dwelling older adults. American Journal of Geriatric Psychiatry. 2005 Jun; 13(6): 450-9.

Correspondence and reprint requests to Michael A. Rapp, Dept. of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Pl., Box 1240, New York, NY 10029-6574.

Objectives: The authors examined the association between neuropsychological tests of executive functioning and episodic memory and functional disability in nursing home residents versus community-dwelling older adults. METHODS: The neuropsychological performance of 96 residents from the Jewish Home and Hospital, Bronx, NY and 192 gender- and age-matched older adults from residential communities in the New York metropolitan area was assessed in eight tasks (Word List Recall, Delayed Recall, Recognition, Boston Naming, Verbal Fluency, Trailmaking A and B, and Digit Symbol Substitution). Functional status was derived from the Clinical Dementia Rating scale (CDR) extended activities of daily living scores. Regression analyses were performed to test for differences in cross-sectional age-gradients for cognitive and functional status between nursing home residents and community-dwellers. Furthermore, regression analyses, controlling for age, gender, dementia status, and education, were performed to determine the association between neuropsychological performance and functional status, comparing domains of executive functioning and memory. RESULTS: Community-dwelling older adults showed age-related deficits both in overall cognitive status and functional disability, which were larger in nursing home residents. Executive functioning was associated with functional disability beyond the effects of age, gender, education, dementia status, residential status, overall cognitive status, memory, and cognitive speed. CONCLUSION: Executive functioning is associated with functional deficits in both community-dwelling older adults and nursing home residents. Measures of executive functioning may prove useful in intervention studies aimed at delaying institutionalization.

PMID: 15956264 [PubMed - in process]
Anthony H. Risser | | |

Wednesday, June 15, 2005

Abstract of the Day: Neuropsychological Tests Accurately Predict Conversion to Alzheimer Disease

Mary C. Tierney, PhD, Christie Yao, Alex Kiss, PhD and Ian McDowell, PhD. Neuropsychological tests accurately predict incident Alzheimer disease after 5 and 10 years. Neurology 2005; 64: 1853-1859.

From the Geriatric Research Unit (Dr. Tierney and C. Yao) and Research Design and Biostatistics (Dr. Kiss), Sunnybrook & Women’s College Health Sciences Centre, Toronto; Department of Family and Community Medicine (Dr. Tierney), University of Toronto; and Department of Epidemiology & Community Medicine (Dr. McDowell), University of Ottawa, Ontario, Canada.

Address correspondence and reprint requests to Dr. Mary C. Tierney, Director, Geriatric Research Unit, A145, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, Canada, M4N 3M5;

Objective: To determine whether neuropsychological tests accurately predict incident Alzheimer disease (AD) after 5 and 10 years in participants of the Canadian Study of Health and Aging (CSHA) who were initially nondemented.

Methods: The CSHA was conducted in three waves: CSHA-1 (1991 to 1992), CSHA-2 (1996 to 1997), and CSHA-3 (2001 to 2002). The 10-year prediction study included those who completed neuropsychological testing at CSHA-1 and received a diagnostic assessment at CSHA-3 (n = 263). The 5-year prediction study included those who completed neuropsychological testing at CSHA-2 and received a diagnostic assessment at CSHA-3 (n = 551). The diagnostic workup for dementia at CSHA-3 was formulated without knowledge of neuropsychological test performance at CSHA-1 or CSHA-2. The authors excluded cases with a baseline diagnosis of dementia or a prior history of any condition likely to affect the brain. Age and education were included in all analyses as covariates.

Results: In the 10-year follow-up study, only one test (short delayed verbal recall) emerged from the forward regression analyses. The model with this test and two covariates was significant, 2 (3) = 31.61, p < 0.0001 (sensitivity = 73%, specificity = 70%). In the 5-year follow-up study, three tests (short delayed verbal recall, animal fluency, and information) emerged from the forward logistic regression analyses. The model was significant, 2 (5) = 91.34, p < 0.0001 (sensitivity = 74%, specificity = 83%). Both models were supported with bootstrapping estimates.

Conclusions: In a large epidemiologic sample of nondemented participants, neuropsychological tests accurately predicted conversion to Alzheimer disease after 5 and 10 years.

Anthony H. Risser
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Tuesday, June 14, 2005

Growing Neurons From Stem Cells in the Lab

A Reuters report, published in a number of different sources, including Wired News:
Stem Cells Get Brainy 
By Reuters
04:04 PM Jun. 13, 2005 PT

WASHINGTON -- Scientists working in mice said they had found a way to identify master cells in the brain and grow them in large batches -- a potential way of helping patients grow their own brain tissue transplants.


"We've isolated for the first time what appears to be the true candidate stem cell," said Dennis Steindler of the University of Florida, who worked on the study.

"There have been other candidates but in this case we used a special microscope that allows us to watch living cells over long periods of time through a method called live-cell microscopy, so we've actually witnessed the stem cell give rise to new neurons. Possibly a different method may come up to identify the mother of all stem cells, but we're confident this is it."

Writing in the Proceedings of the National Academy of Sciences, the researchers said they also found an efficient way to make the cells multiply.

"It's like an assembly line to manufacture and increase the number of brain cells," said Dr. Bjorn Scheffler, a neuroscientist at the University of Florida who led the study.

"We can basically take these cells and freeze them until we need them. Then we thaw them, begin a cell-generating process, and produce a ton of new neurons."

[ ... Read the rull report ... ]
Anthony H. Risser | | |

Sunday, June 12, 2005

Neuroanatomy in the News!

From tomorrow's Washington Post, an article about the relevance of the architecture of crossed motor and sensory pathways (cool!):
What Crosses Our Minds When Danger's Afoot
By David Brown
Washington Post Staff Writer
Monday, June 13, 2005; Page A08

One of the more mysterious and less-explored observations about human anatomy is also one of the oldest, going all the way back to the Father of Medicine.

"If the wound be situated on the left side [of the head], the convulsion attacks the right side of the body," Hippocrates noted in the 4th century B.C. The Greek physician recognized that trauma on one side of the head could cause a seizure limited to or, more likely, starting in the limbs on the opposite side of the body.

About A.D. 150, a physician named Aretaeus the Cappadocian extended this observation in a truly remarkable way.

He noticed that if the right side of the head was severely damaged, the left side of the body would be paralyzed. However, if the damage was in the right side of the spinal cord instead, the paralysis would be on the same side. He then came up with an explanation.

"The cause of this is the interchange in the origins of the nerves, for they do not pass along on the same side . . . until their terminations," he wrote, according to an account in the 1994 book "Origins of Neuroscience" by medical historian Stanley Finger. Each nerve "passes over to the other side from that of its origin, [separating from] each other in the form of the letter X."
[ ... Read the full article ... ]
Anthony H. Risser | | |

Abstract of the Day: Web-Based Intervention in Traumatic Brain Injury

Wade SL, Wolfe C, Brown TM, & Pestian JP. Putting the Pieces Together: Preliminary Efficacy of a Web-Based Family Intervention for Children with Traumatic Brain Injury. Journal of Pediatric Psychology. 2005 Jul; 30(5): 437-442.

Division of Pediatric Physical Medicine and Rehabilitation, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.

OBJECTIVE: To report preliminary efficacy data from a Web-based family problem-solving intervention to improve parent and child adaptation. METHOD: Eight parents and six children with moderate to severe traumatic brain injury (TBI) who were injured more than 15 months earlier (M = 16 months) participated in the intervention. Families were given computers, Web cameras, and high-speed Internet access. Weekly videoconferences with the therapist were conducted after they completed self-guided Web exercises on problem-solving, communication, and antecedent behavior management strategies. RESULTS: Paired t tests comparing pre- and post-intervention scores revealed significant improvements in injury-related burden, parental psychiatric symptoms, depression, and parenting stress. There were also significant reductions in antisocial behaviors in the injured child, but not in self-reported depressive symptoms. CONCLUSIONS: These findings suggest that a computer-based intervention may successfully be used to improve both parent and child outcomes following TBI in children.

PMID: 15944171 [PubMed - as supplied by publisher]
Anthony H. Risser | | |

Friday, June 10, 2005

Business World: Biogen Idec, Elan, & Tysabri (Natalizumab)

From today's Boston Globe:
Biogen MS drug gets lift from reports
Medical journal suggests Tysabri may make a return
By Jeffrey Krasner
The Boston Globe
10 June 2005

Biogen Idec Inc.'s drug Tysabri might be safely given to multiple sclerosis patients if they are carefully monitored for an often fatal brain disease, according to articles in The New England Journal of Medicine.

Three patients taking the medication have contracted the disease, known as PML, and a fourth case is suspected. But some doctors writing in the journal speculated that monitoring might make it possible to discontinue treatment with Tysabri -- known generically as natalizumab -- and treat patients in time to prevent PML from developing into a life-threatening illness.
[ ... Read the full article ... ]

(Reminder: "PML" is the abbreviation for "progressive multifocal leukoencephalopathy.")

Note: The NEJM material is accessible, online "early release" material, found on the journal's content homepage, includes the PML case studies, two editorials, and correspondence. The set will appear in the printed version of the journal on the 28th of July.

BRIEF REPORT:  G. Van Assche et al. Progressive Multifocal Leukoencephalopathy after Natalizumab Therapy for Crohn's Disease

BRIEF REPORT:  B.K. Kleinschmidt-DeMasters & K.L. Tyler. Progressive Multifocal Leukoencephalopathy Complicating Treatment with Natalizumab and Interferon Beta-1a for Multiple Sclerosis

BRIEF REPORT:  A. Langer-Gould et al. Progressive Multifocal Leukoencephalopathy in a Patient Treated with Natalizumab

EDITORIAL:  J.R. Berger & I.J. Koralnik. Progressive Multifocal Leukoencephalopathy and Natalizumab — Unforeseen Consequences

EDITORIAL:  J.M. Drazen. Patients at Risk

CORRESPONDENCE:  Natalizumab and Progressive Multifocal Leukoencephalopathy

Anthony H. Risser | | |

Wednesday, June 08, 2005

HAL-5 (Hybrid Assistive Limb): Possibilities to Mine for Apps for Older or Disabled Persons?

From the Australian news network, ABC:
Robot suit to help create 'supermen'
Tuesday, June 7, 2005. 3:18pm (AEST)
Full report

Japan has taken a step into the world of science fiction with the release of a robot suit that can help workers lift heavy loads or assist people with disabilities climb stairs.

"Humans may be able to mutate into supermen in the near future," said Yoshiyuki Sankai, a professor and engineer at Tsukuba University who led the project.

The 15-kilogram battery-powered suit, code-named HAL-5, detects muscle movements through electrical-signal flows on the skin surface and then amplifies them.

It can also move on its own accord, enabling it to help elderly or handicapped people walk, its developers say.

The prototype suit will be displayed at the World Exposition that is under way in Aichi prefecture, central Japan.
Additionally, here is a Japan Times article from 2004 about Dr. Yoshiyuki Sankai.

Finally, from a January 2005 interview with International Herald Tributne/, available in full by clicking here:
"There is still much we Japanese researchers can do for those who are in need, particularly with the aging society,'' he says.

Rather, Sankai has faith in the idea that Japanese hold a unique sense of appreciation for robots, which could direct the future course of robotics.

"Japanese tend to view robots as heroes, while in many other countries, such as the United States, robots are often portrayed as villains,'' Sankai says.

Sankai became attached to robots and cyborgs as an elementary school student thanks to Ishinomori's "Cyborg 009," a cartoon whose protagonist is half-human, half-machine.

"I knew right away that I wanted to become a researcher working on robotics, and I started right away to experiment,'' he says.

His curiosity led him to catch frogs in a nearby castle moat in his native Okayama. He hooked up the frogs' legs to a generator he had assembled and administered electric shocks at different levels to see when the muscles contracted.

That knowledge helped him later in life when he studied the effects of electric pulses on the muscles of paralyzed people.

"Thanks to the experience I had as a child, I can say I am the person I am today,'' Sankai says.

Sankai's latest creation, which includes a new robot suit for the upper body, will be among several automatons highlighted at the World Exposition 2005 in Aichi Prefecture that kicks off in March.

But he says his work is far from complete; it will be a little while before a machine is able to perfectly assist people with disabilities.

"We're finding a new challenge every day,'' Sankai says.
Anthony H. Risser | | |

Legal World: Amgen, GDNF Clinical Trial, and Parkinson Disease

From The New York Times, concerning glial cell line-derived neurotrophic factor (GDNF):
Judge Rejects Patients' Suit to Get Test Drug
The New York Times
Published: June 8, 2005

A federal judge has denied a request by two people with Parkinson's disease that he order Amgen to continue giving them a drug they used in a clinical trial that the company discontinued.

The lawsuit raised questions about the rights of patients in clinical trials. The patients accused Amgen, the world's largest biotechnology company, of treating them as "mere guinea pigs" and argued that the company had a legal and moral obligation to continue the treatment, which they said had eased their symptoms.

But Judge P. Kevin Castel of United States District Court in Manhattan ruled Monday that Amgen was under no contractual obligation to continue supplying the drug. He said that the informed consent forms signed by the patients before participating in the trial explicitly acknowledged Amgen's right to terminate it.
[ ... Read the full article ... ]
Anthony H. Risser
| | |

Tuesday, June 07, 2005

Business World: Everest Biomedical

From the company's press release:
Everest Biomedical Forms Research Alliance With NYU
ST. LOUIS, June 7 /PRNewswire/ -- Everest Biomedical Instruments Company, based in St. Louis, announced today its alliance with New York University School of Medicine's Brain Research Laboratory (BRL). The agreement provides Everest with exclusive rights to a number of patents and patent applications from the laboratory. BRL's patented information covers the fields of electroencephalography (EEG), neurodiagnostics, neurotherapy, brain function scanning and anesthesia, analgesia and amnesia monitoring. Terms of the agreement were not disclosed.

Access to BRL's intellectual property will accelerate Everest's commercialization of novel brain-state neurological assessment devices. Designed to assist physicians in screening and evaluating patients with an altered mental status, Everest's new product plans include creation of a handheld device, the BrainScope(TM), that produces automatic, functional brain-state assessments. The technology could lead to improved results and more efficient care for patients suffering from traumatic brain injuries, strokes, seizures, Alzheimer's disease and various psychiatric disorders.
[ ... Read the full press release ... ]
Anthony H. Risser | | |

Monday, June 06, 2005

Business World: Neuren Pharm and Glypromate

From The New Zealand Herald
NZ brain drug gets fast-track testing
By Peter Nowak and Monique Devereux
The New Zealand Herald
 07 June 2005
A New Zealand-developed drug that reduces the number of brain cells dying after injury has been fast-tracked through trials, meaning it could be on the market two years earlier than planned.

The drug, which is being developed in Auckland by Neuren Pharmaceuticals, could help hundreds of thousands of people who have suffered brain damage through road accidents, strokes and heart attacks.

The United States Food and Drug Administration (FDA) yesterday told Neuren it could proceed to phase III testing - the final stage before releasing the drug glypromate to the market - by 2006.

The move saves Neuren the $6.5 million cost of setting up and running phase II trials.

Reaction to the announcement pushed the company's shares up 25 per cent on the Australian Stock Exchange yesterday.

Neuren chief executive David Clarke said it was the first time an Australasian pharmaceutical company had been given FDA permission to skip phase II testing.
[ ... Read the full article ... ]

From the Neuren website, about glypromate:
Glypromate® (or Glycine-Proline-Glutamate) is a naturally occurring small molecule neuroprotectant, derived from IGF-1 (Insulin-like Growth Factor), that is produced in the brain but does not bind to IGF-1 receptors."
Anthony H. Risser | | |

The Blue Brain Project (BBP)

A collaboration between IBM and Dr. Henry Markram , founder of the Brain/Mind Institute at the Ecole Polytechnique Fédérale de Lausanne (EPFL) (Switzerland), has been announced that will lead to the creation of computer-simulated neocortical columns.

According to the EPFL website:
"The first phase of BBP will be to replicate in software, a column of the Neocortex (NCC) with 10,000 morphologically complex neurons with unprecedented detail for high-speed simulations.

The second and subsequent phases will be to simplify the NCC and expand the simulation to brain regions and eventually the whole brain.

An accurate replica of the neocortical column is the essential first step to simulating the whole brain and will also provide the link between genetic and molecular levels of brain function and high-level cognitive functions.

The neocortical column is considered to be the elementary network of neurons that can act as a unit exhibiting most of the complex functions of the brain."
Today's IBM press release reads in part:
"Yorktown Heights, NY and Lausanne, Switzerland, June 6, 2005 – IBM and The Ecole Polytechnique Fédérale de Lausanne (EPFL) are today announcing a major joint research initiative – nicknamed the Blue Brain Project – to take brain research to a new level.

Over the next two years scientists from both organizations will work together using the huge computational capacity of IBM’s eServer Blue Gene supercomputer to create a detailed model of the circuitry in the neocortex – the largest and most complex part of the human brain. By expanding the project to model other areas of the brain, scientists hope to eventually build an accurate, computer-based model of the entire brain.

Relatively little is actually known about how the brain works. Using the digital model scientists will run computer-based simulations of the brain at the molecular level, shedding light on internal processes such as thought, perception and memory. Scientists also hope to understand more about how and why certain microcircuits in the brain malfunction – thought to be the cause of psychiatric disorders such as autism, schizophrenia and depression.

“Modeling the brain at the cellular level is a massive undertaking because of the hundreds of thousands of parameters that need to be taken into account,” said Henry Markram, the EPFL professor heading up the project. “IBM has unparalleled experience in biological simulations and the most advanced supercomputing technology in the world. With our combined resources and expertise we are embarking on one of the most ambitious research initiatives ever undertaken in the field of neuroscience.”
[ ... Read the full press release ... }

The IBM webpage that outlines the BBP is linked here.
Anthony H. Risser | | |

Thursday, June 02, 2005

Numerical-Spatial Cognitive Interactions of the Parietal Lobe

The functions and dysfunctions of the parietal lobes are often the most difficult of the four cerebral lobes for a student to understand when learning about brain-behavior relations. This month's issue of Nature Reviews Neuroscience includes free full-text access to a review paper about some of these parietal functions; it is a reasonably good (albeit technical) read.

(By the way, this issue of the journal also includes a poster-sized .pdf graphic of aspects of post-synaptic functioning.)

Edward M. Hubbard, Manuela Piazza, Philippe Pinel, & Stanislas Dehaene. Interactions between number and space in parietal cortex. Nature Reviews Neuroscience. 2005; 6, 435-448 [doi:10.1038/nrn1684]

Inserm Unit 562 'Cognitive Neuroimaging' Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, F94101 Orsay, France.


Since the time of Pythagoras, numerical and spatial representations have been inextricably linked. We suggest that the relationship between the two is deeply rooted in the brain's organization for these capacities. Many behavioural and patient studies have shown that numerical–spatial interactions run far deeper than simply cultural constructions, and, instead, influence behaviour at several levels. By combining two previously independent lines of research, neuroimaging studies of numerical cognition in humans, and physiological studies of spatial cognition in monkeys, we propose that these numerical–spatial interactions arise from common parietal circuits for attention to external space and internal representations of numbers.

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

Business World: Biogen Idec, Elan, & Tysabri (Natalizumab) (cont.)

Additional information in follow-up to this morning's Boston Globe report, from Bloomberg:
Elan, Biogen Decline on Report of New Tysabri Illness

June 2 (Bloomberg) -- Shares of Elan Corp. and Biogen Idec Inc. tumbled after a fourth possible case of a rare and often fatal nerve disorder was reported in a patient taking the companies' withdrawn Tysabri multiple-sclerosis drug.

Biogen and Elan are investigating the newest report of a Tysabri patient with symptoms consistent with the disorder, Lenore Gelb, a U.S. Food and Drug Administration spokeswoman, said today. Elan shares fell 83 cents, or 13 percent, to 5.47 euros in Dublin. Biogen lost 4.3 percent on the Nasdaq Stock Market. The Boston Globe reported the case earlier today.

The report hasn't been confirmed to be the disease, called progressive multifocal leukoencephalopathy, as have three other cases, Gelb said. Biogen and Elan withdrew Tysabri Feb. 28 after the potential $1 billion drug was linked to the disorder. Two of three patients who developed the disease have died.
[ ... Read the full report ... ]
Anthony H. Risser | | |

Business World: Biogen Idec, Elan, & Tysabri (Natalizumab)

From today's Boston Globe:
A fourth death may be tied to Biogen's MS drug
Finding could be blow to marketplace hopes
By Jeffrey Krasner,
Boston Globe Staff
June 2, 2005

Biogen Idec Inc. has told the Food and Drug Administration that a fourth patient may have contracted a potentially deadly brain disease after being treated with the company's multiple sclerosis drug Tysabri.
[ ... Read the full article ... ]
Anthony H. Risser | | |

Upcoming Event: Gaithersburg, MD, 17 June 2005

From the FDA:

DATE AND TIME: June 17, 8:30 a.m.
LOCATION: Hilton Washington, DC North/Gaithersburg, Salons A, B and C, 620 Perry Pkwy., Gaithersburg, MD.
CONTACT: Janet L. Scudiero, Center for Devices and Radiological Health, 301-594-1184.
Event webpage

The committee will hear a presentation on the FDA Critical Path Initiative and a presentation by the Office of Surveillance and Biometrics in the Center for Devices and Radiological Health outlining their responsibility for the review of postmarket study design. The committee will also hear an update on the status of recent devices brought before the committee. Subsequently, the committee will discuss, make recommendations, and vote on a premarket approval application for a selective head cooling system intended for use in infants 36 weeks of gestation or older at risk for moderate to severe hypoxic-ischemic encephalopathy (HIE) to prevent or reduce the severity of HIE.

Background material and meeting information will become available no later than one business day before the meeting (Simply scroll down to the appropriate committee heading).

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to the contact person by June 3, 2005. Oral presentations from the public will be scheduled for approximately 30 minutes at the beginning of committee deliberations and for approximately 30 minutes near the end of the deliberations. Time allotted for each presentation may be limited. Those desiring to make formal oral presentations should notify the contact person before June 3, 2005, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation. Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.

FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact AnnMarie Williams at 240-276-0450, ext. 113, at least 7 days in advance of the meeting.

Contact Person:
Janet L. Scudiero, Center for Devices and Radiological Health (HFZ-410), Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD 20850, 301-594-1184

Advisory Committee Telephone Information Line:
Please call the Information Line for up-to-date information on this meeting, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512513.
Anthony H. Risser | | |

Wednesday, June 01, 2005

Cognitive Dysfunction in Individuals with Cancer

Advances in treatment and care have improved the survival rates of patients diagnosed with cancer. Survival raises issues of treatment-related morbidity, symptom experience, and concern over the incidence of cognitive dysfunction. Methodological concerns in understanding these issues include (a) making sure one knows baseline levels of symptoms and cognitive problems in order to best determine the impact of treatment, (b) accessing the ability to use follow-up assessments of test measures appropriate to the functions of concern and the temporal issues of concern, and (c) recognizing that survivorship from cancer places an individual back on a life-span developmental track that includes both age-relevant changes in normal function and abnormal changes consequent upon other medical disorders, such as stroke or neurodegenerative disease processes.

Today's new issue of The Journal of the National Cancer Institute includes a brief communication and an editorial in this realm of clinical research. Both are available in free full-content form:

Lara H. Heflin, Beth E. Meyerowitz, Per Hall, Paul Lichtenstein, Boo Johansson, Nancy L. Pedersen, & Margaret Gatz. Cancer as a risk factor for long-term cognitive deficits and dementia. Journal of the National Cancer Institute. 2005; 97: 854–856.
Read the full Brief Communication.

Jeffrey S. Wefel & Christina A. Meyers. Cancer as a risk factor for dementia: A house built on shifting sand. Journal of the National Cancer Institute, 2005. 97: 788-789.
Read the full Editorial
Anthony H. Risser | | |

Deep Throats, Hacked Minds, and Sleepy Heads

First, a non-neuro "thank you" to The Washington Post and Mark Felt for the roles they played all those years ago. Today's lead editorial in the Post (free registration required).

Second, a "thank you" to for their kind words earlier today about this blog.

Finally, an article from the new issue of The American Psychological Association Monitor about the brain during periods of fatigue:
Sleepy heads
A pilot Air Force study finds individual differences in how brains respond when tired.
The APA Monitor
June 2005
Print version: page 20


When on a long plane flight, do you ever wonder how fatigue affects your pilot? So does the U.S. Air Force. In the June issue of Behavioral Neuroscience (Vol. 119, No. 3), military psychologists report on a study that revealed different patterns of brain activity that corresponded with individual differences in how tired pilots performed mentally.

The study launches a new approach for research into ways to reverse the cognitive effects of sleep deprivation and to improve job safety among pilots and others who work long, demanding hours.

At the Air Force Research Laboratory at Brooks City-Base in San Antonio, a Fatigue Countermeasures Team led by John Caldwell, PhD, compared how well fighter pilots and nonpilots performed certain tasks when snooze-deprived, and related that performance to brain activity via functional magnetic resonance imaging (fMRI). The results are sufficiently intriguing to warrant further study with larger samples and more rigorous controls, say the researchers.

It seems that sleepy people had sleepy brains, or, more specifically, less activity in specific regions of the cortex. The Texas team also confirmed and extended previous findings that while on average, sleep deprivation hammers thinking skills, everybody's different--and no one knows why. This perplexing phenomenon prompted the Air Force psychologists to take the problem into the lab.

"As is often the case, this initial study is not perfect, but it will motivate bigger studies designed to more directly test the hypotheses," says Sean P.A. Drummond, PhD, a psychologist with the Laboratory for Sleep & Behavioral Neuroscience at the University of California, San Diego, and the VA San Diego Healthcare System. "One of the holy grails of sleep deprivation research right now is the quest to find biological markers of individual vulnerability to sleep deprivation."
[ ... Read the full article ... ]
Anthony H. Risser | | |