Saturday, October 30, 2004

In The Weeklies

Here are some relevant highlights from this week’s major scientific and medical weeklies:

New England Journal of Medicine
28 October 2004

This week’s issue includes several papers of interest, two on the topic on bacterial meningitis and the third is a case study of a patient with a frontal lobe lesion: Bacterial Meningitis — A View of the Past 90 Years by M. N. Swartz; Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis by D. van de Beek and colleagues; and Case 33-2004 — A 34-Year-Old Man with a Seizure and a Frontal-Lobe Brain Lesion by E. N. Eskandar and colleagues.

Science
29 October 2004

This week’s issue includes a research study that has been reported in quite a few public media outlets over the past few days in terms of the relation between stress and forgetfulness. Here is the abstract:
Birnbaum SG, Yuan PX, Wang M, Vijayraghavan S, Bloom AK, Davis DJ, Gobeske KT, Sweatt JD, Manji HK, Arnsten AF. Protein kinase C overactivity impairs prefrontal cortical regulation of working memory. Science. 2004 Oct 29; 306(5697): 882-4.

Department of Neurobiology, Yale Medical School, 333 Cedar Street, New Haven, CT 06520-8001, USA.

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

PMID: 15514161 [PubMed - in process]

Friday, October 29, 2004

Laser-Based Neural Stimulation

A press release from Vanderbilt University discusses research seeking to develop more precise ways to stimulate individual neurons through the use of laser light:

Stimulating Nerve Cells with Laser Precision

Newswise — Biomedical engineers and physicians at Vanderbilt University have brought the day when artificial limbs will be controlled directly by the brain considerably closer by discovering a method that uses laser light, rather than electricity, to stimulate and control nerve cells.

The researchers have discovered that low-intensity infrared laser light can spark specific nerves to life, exciting a leg or even individual toes without actually touching the nerve cells.

“This technique brings nerve stimulation out of the Dark Ages,” said Vanderbilt Assistant Professor of Biomedical Engineering and Neurological Surgery Anita Mahadevan-Jansen. “Much work is going on around the world trying to make electric nerve stimulation better, but the technique is inherently limited. Using lasers instead, we can simultaneously excite and record the responses of nerve fibers with much greater precision, accuracy and effectiveness.”

The method was developed by Mahadevan-Jansen; her husband Duco Jansen, associate professor of biomedical engineering and neurological surgery; Dr. Peter Konrad and Dr. Chris Kao of Vanderbilt Neurological Surgery, both assistant professors of neurological surgery; and biomedical engineering doctoral student Jonathon Wells.

In an experiment with rats, the scientists used a laser to stimulate the sciatic nerve and to control muscles in the animal’s hind leg and individual toes, demonstrating accuracy beyond the limitations of electrical stimulation. Immediately following the experiment, the rats regained full use of their legs with no signs of weakness or damage.

Konrad, who is also director of the Vanderbilt Functional Neurosurgery program, points out that neurostimulation is ideally done cell by cell. “The problem with the conventional electrical method is that we have a large zone around our target neuron that also is affected simply because of the way electricity travels throughout the tissue. Using light to stimulate neurons, we can pick off a single neuron without affecting the other neurons around it.”

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

Thursday, October 28, 2004

Abstract of the Day: Lobar Neurodegeneration

Gorno-Tempini ML, Rankin KP, Woolley JD, Rosen HJ, Phengrasamy L, Miller BL. Cognitive and behavioral profile in a case of right anterior temporal lobe neurodegeneration. Cortex. 2004 Sep-Dec; 40(4-5): 631-44.

University of California San Francisco Department of Neurology, San Francisco, CA, USA.

Semantic dementia (SD) is a clinical variant of frontotemporal lobar degeneration (FTLD) characterized by progressive deterioration of semantic memory with relative sparing of other cognitive functions. It is associated with mainly left anterior temporal atrophy, and is also referred to as "left-temporal lobe variant" of FTLD. Recently, patients with mainly right-sided atrophy, or "right-temporal lobe variant"(RTLV), have been described. While some authors have reported that the initial and most significant deficit in these right-sided cases is a difficulty in recognizing famous people, others have observed that major behavioral abnormalities are the presenting symptoms. Here we report a detailed neuropsychological, language, behavioral and neuroimaging assessment of JT, a case of right temporal lobe variant of FTLD. JT showed early and prominent behavioral changes accompanied by a severe impairment in recognizing foods by their look, flavor or name. Later she also developed a difficulty in recognizing familiar people and objects. Standardized caregiver questionnaires of JT's pre- and post-morbid personality and interpersonal functioning showed that she went from being a flexible, dominant, extraverted, person to showing rigid, submissive and introverted behaviors. Her levels of neuroticism significantly increased, while her scores on agreeableness and cognitive and emotional empathy dropped. Voxel-based morphometry (VBM) showed most significant atrophy in the right amygdala/anterior hippocampal complex and collateral sulcus, extending to the right insula. We discuss the atypical cognitive and behavioral features of this case of RTLV of FTLD and stress the importance of behavioral changes and atypical semantic deficits for early diagnosis.

PMID: 15505973 [PubMed - in process]

Business World: EMD 281014 and Insomnia

From the New York Times website:

Lilly to Buy Insomnia Compound
By THE ASSOCIATED PRESS
Published: October 28, 2004
Filed at 11:21 a.m. ET

INDIANAPOLIS (AP) -- Eli Lilly and Co. will pay a German pharmaceutical company $29 million for the rights to an experimental compound the Indianapolis-based drug maker hopes can become its first product to treat insomnia.

The compound, discovered by Merck KGaA, has the potential to be a new way to treat sleep disorder, without being addictive or causing unwelcome side effects, said Darryle D. Schoepp, vice president of neuroscience discovery research at Lilly.

"This could be really a very important medical advance in the treatment of sleep disorders,'" he said Wednesday.

In addition to purchasing the compound, Lilly will make milestone payments to Merck as the drug moves through testing, plus pay royalties on any sales. Merck keeps rights to co-promote the compound in certain countries.

Called EMD 281014, the molecule has undergone the first stage of human testing -- tests that showed it is safe in humans, Schoepp said.

[ ... Read the full article ... ]. (free registration required)

Parkinson's Disease

The CBS show "60 Minutes Wednesday" aired a piece last evening, A Hole in His Head, which accounts the story of one person's pallidotomy in 1995 and visits with him again in 2004. From CBS:
Parkinson's disease is a heartbreaking illness that causes frozen, stone-faced stillness in those afflicted. Correspondent Morley Safer reports on the story of one man, Fred Amphlett of Bristol, England, who had been a prisoner of Parkinson's for years.

When Safer first met him in 1995, he was about to undergo an operation called a pallidotomy, once used by doctors to ease the agonies of Parkinson's. It was not a cure, nor was it for everyone. But for Amphlett, it was his last hope.
[ ... Read the full transcript ... ]

Wednesday, October 27, 2004

Monkey "Closed Loop" Manipulation

From Wired News, another presentation from Neuroscience 2004:
Advent of the Robotic Monkeys
By David Cohn
01:00 PM Oct. 26, 2004 PT Wired News

If a monkey is hungry but has his arms pinned, there's not much he can do about it. Unless that monkey can control a nearby robotic arm with his brain.

And that's exactly what the monkey in Andrew Schwartz 's neurobiology lab at the University of Pittsburgh can do, feeding himself using a prosthetic arm controlled solely by his thoughts.

If mastered, the technology could be used to help spinal cord injuries, amputees or stroke victims. "I still think prosthetics is at an early stage ... but this is a big step in the right direction," said Chance Spalding, a bioengineering graduate student who worked on the project.

[snip]

The unique aspect of Schwartz's research is that he conducted what is known as "closed loop" brain experiments. In a "closed loop" experiment, the monkey is conscious of the robotic arm and is making an effort to control it. Monkeys in previous experiments did not understand that they were having an effect on the world at all. Duke University performed such prosthetic arm experiments as far back as 2000. In one case they even sent the electrode signals over the internet , allowing the monkey to move an arm 600 miles away at MIT.

"The open loop experiment was really very crude," said Schwartz. "The closed loop introduces us into a whole new field because the animal actually sees the arm and the consequence of what it is doing." For Schwartz's monkey the robotic arm is incorporated into its mental body representation, making it an extra limb.

[ ... Read the full report ... ]

Tuesday, October 26, 2004

Business World: Vasogen and Parkinson's Disease

A company press release concerning a presentation at Neuroscience 2004:
Vasogen's VP025 Provides a Neuroprotective Effect in Preclinical Model of Parkinson's Disease

TORONTO, Oct. 26 /PRNewswire-FirstCall/ - Vasogen Inc. (NASDAQ:VSGN; TSX:VAS), a researcher and developer of immune modulation therapies targeting chronic inflammation, today announced the presentation of preclinical research demonstrating the ability of VP025 to provide a significant neuroprotective effect in a model of Parkinson's disease. The research, carried out by the Department of Anatomy/Neuroscience, Biosciences Institute, University College Cork, Ireland, was presented at Neuroscience 2004, the Society for Neuroscience's 34th Annual Meeting in San Diego.

"The ability of VP025 to offer a protective effect in the brain and reduce neuron death in this preclinical model suggests that this drug may have potential in the treatment of Parkinson's disease," said Dr. Aideen Sullivan, principal investigator for this study at University College Cork. "It is also encouraging to note that these data are consistent with other research being presented at this conference this week, which highlight the positive anti-inflammatory effects of VP025 in other preclinical models."

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

Sunday, October 24, 2004

Olfactory Bulb Stem Cell Transplants and ALS

A number of news reports are beginning to be published from presentations at Neuroscience 2004, the ongoing conference of the Society for Neuroscience. Here is one press release from Johns Hopkins Medical Institutions concerning a presentation about amyotrophic lateral sclerosis (ALS):
Olfactory Bulb Stem Cells and Lou Gehrig's Disease
Johns Hopkins researchers have found that transplants of mouse stem cells taken from the adult brain's olfactory bulb can delay symptoms and death in a mouse model of amyotrophic lateral sclerosis, or Lou Gehrig's disease.
Read the abstract for Transplantation of Adult Olfactory Bulb Neural Stem Cells Delays Disease Onset and Prolongs Survival in a Mouse ALS Model by L.J. Martin and Z. Liu.

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

Friday, October 22, 2004

In The Weeklies

Here are some relevant highlights from this week’s major scientific and medical weeklies:

Journal of the American Medical Association
20 October 2004
This week’s JAMA has a number of contributions on the subject of the diagnosis and treatment of strokes.

New England Journal of Medicine
21 October 2004
This week’s issue contains a research paper and an editorial on the topic of Tuberculous meningitis: Abstract for Dexamethasone for the Treatment of Tuberculous Meningitis in Adolescents and Adults by Thwaites and colleagues and an extract of the editorial, Adjunctive Steroids for Tuberculous Meningitis - More Evidence, More Questions by Quagliarello.

Lancet
23 October 2004
The current issue includes the paper, Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: A randomised, double-blind, placebo-controlled trial by Filippi and colleagues.

Science
22 October 2004
This week’s issue has a special topical theme, gene expression.

It includes the report, A Chromosome 21 Critical Region Does Not Cause Specific Down Syndrome Phenotypes, by L. E. Olson, J. T. Richtsmeier, J. Leszl, and R. H. Reeves (pp. 687-690) and a perspective, The Critical Region in Trisomy 21, by D. L. Nelson and R. A. Gibbs (pp. 619-621).

Nature
21 October 2004
This week’s Nature includes the letter, Neural correlates of mental rehearsal in dorsal premotor cortex, by P. Cisek and J. F. Kalaska, excerpted below:

"Behavioural and imaging studies suggest that when humans mentally rehearse a familiar action they execute some of the same neural operations used during overt motor performance. Similarly, neural activation is present during action observation in many of the same brain regions normally used for performance, including premotor cortex. Here we present behavioural evidence that monkeys also engage in mental rehearsal during the observation of sensory events associated with a well-learned motor task. Furthermore, most task-related neurons in dorsal premotor cortex exhibit the same activity patterns during observation as during performance, even during an instructed-delay period before any actual observed motion. This activity might be a single-neuron correlate of covert mental rehearsal."

Neuroscience 2004 Conference Begins Tomorrow

Neuroscience 2004, the Society For Neuroscience's 34th Annual Meeting, begins in San Diego tomorrow and continues until Wednesday, the 27th. To read more about the conference and the Society, click here.

Wednesday, October 20, 2004

Imaging in the Initial Evaluation of Acute Stroke Symptoms

This week's free access full-text paper in the new issue of the Journal of the American Medical Association addresses the relative value of CT vs. MRI imaging in the initial evaluation of acute CVA symptoms. Click here for the full paper; the abstract follows:

Chelsea S. Kidwell, MD; Julio A. Chalela, MD; Jeffrey L. Saver, MD; Sidney Starkman, MD; Michael D. Hill, MD; et al. Comparison of MRI and CT for Detection of Acute Intracerebral Hemorrhage. JAMA. 2004; 292: 1823-1830.

ABSTRACT

Context.  Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated.

Objective.  To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms.

Design, Setting, and Patients.  A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT.

Main Outcome Measures.  Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers.

Results.  The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P less than .001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT—each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT.

Conclusion.  MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

Tuesday, October 19, 2004

When is it Good to Forget?

Anyone who's seen the movie, Eternal Sunshine of the Spotless Mind, has thought about the question. Many may be surprised that a number of neuroscientists and drug developers have been asking the same question. The issue comes up when thinking of the topic of so-called "cosmetic neurology," but also arises when considering very serious acute mental trauma. Today's Washington Post includes an article exploring this question:
Is Every Memory Worth Keeping?
Controversy Over Pills to Reduce Mental Trauma

By Rob Stein
Washington Post Staff Writer
Tuesday, October 19, 2004; Page A01

[snip]

Proponents say it could lead to pills that prevent or treat PTSD in soldiers coping with the horrors of battle, torture victims recovering from brutalization, survivors who fled the World Trade Center on Sept. 11, 2001, and other victims of severe, psychologically devastating experiences.

"Some memories can be very disruptive. They come back to you when you don't want to have them -- in a daydream or nightmare or flashbacks -- and are usually accompanied by very painful emotions," said Roger K. Pitman, a professor of psychiatry at Harvard Medical School who is studying the approach. "This could relieve a lot of that suffering."

Skeptics, however, argue that tinkering with memories treads into dangerous territory because memories are part of the very essence of a person's identity, as well as crucial threads in the fabric of society that help humanity avoid the mistakes of the past.

"All of us can think of traumatic events in our lives that were horrible at the time but made us who we are. I'm not sure we'd want to wipe those memories out," said Rebecca S. Dresser, a medical ethicist at Washington University in St. Louis who serves on the President's Council on Bioethics, which condemned the research last year. "We don't have an omniscient view of what's best for the world."

Some fear anything designed for those severely disabled by psychic damage will eventually end up being used far more casually -- to, perhaps, forget a bad date or a lousy day at work.

"You can easily imagine a scenario of 'I was embarrassed at my boss's party last night, and I want to take something to forget it so I can have more confidence when I go into the office tomorrow,' " said David Magnus, co-director of Stanford University's Center for Biomedical Ethics. "It's not hard to imagine that it will end up being used much more broadly."

[snip]

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

Neuromarketing: Brand Loyalty and the Brain

Last week's news had several reports about a new functional MRI study looking at taste preferences and brand loyalty. Here is the abstract of that study:
McClure SM, Li J, Tomlin D, Cypert KS, Montague LM, Montague PR. Neural correlates of behavioral preference for culturally familiar drinks. Neuron. 2004 Oct 14; 44(2): 379-87.

Department of Neuroscience, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030 USA.

Coca-Cola((R)) (Coke((R))) and Pepsi((R)) are nearly identical in chemical composition, yet humans routinely display strong subjective preferences for one or the other. This simple observation raises the important question of how cultural messages combine with content to shape our perceptions; even to the point of modifying behavioral preferences for a primary reward like a sugared drink. We delivered Coke and Pepsi to human subjects in behavioral taste tests and also in passive experiments carried out during functional magnetic resonance imaging (fMRI). Two conditions were examined: (1) anonymous delivery of Coke and Pepsi and (2) brand-cued delivery of Coke and Pepsi. For the anonymous task, we report a consistent neural response in the ventromedial prefrontal cortex that correlated with subjects' behavioral preferences for these beverages. In the brand-cued experiment, brand knowledge for one of the drinks had a dramatic influence on expressed behavioral preferences and on the measured brain responses.

PMID: 15473974 [PubMed - in process]


Today's New York Times Science section includes a look at this study and what so-called "neuromarketing" applications might develop.
If Your Brain Has a 'Buy Button,' What Pushes It?
By SANDRA BLAKESLEE
New York Times
19 October 2004

Knowing what brand you are buying can influence your preferences by commandeering brain circuits involved with memory, decision making and self-image, researchers have found.

When researchers monitored brain scans of 67 people who were given a blind taste test of Coca-Cola and Pepsi, each soft drink lit up the brain's reward system, and the participants were evenly split as to which drink they preferred. But when the same people were told what they were drinking, activity in a different set of brain regions linked to brand loyalty overrode their original preferences. Three out of four said that they preferred Coca-Cola.

The study, published in the Oct. 14 issue of the journal Neuron, is the first to explore how cultural messages penetrate the human brain and shape personal preferences.

Circulating in draft form over the last year, the study has been widely discussed by neuroscientists and advertisers, as well as people who worry about the power of commercials in determining consumer behavior.

At issue is whether marketers can exploit advances in brain science to make more effective commercials. Is there a "buy button" in the brain?
[ ... Read the full article ... ] (free registration required)

Monday, October 18, 2004

Imaging Alzheimer Disease - Part 2

Today's Yale Daily News includes an article about last week's announcement about the initiative to examine imaging technologies in the diagnosis of Alzheimer disease. The article is interesting to read of itself, but also because it touches briefly upon the concern of the neuropsychological community about the important role of neuropsychological assessment in the assessment of the cognitive changes that are diagnostically relevant:
Scientists seek earlier Alzheimer's diagnoses
BY ALBERTO MASLIAH
Contributing Reporter
Yale Daily News
Published Monday, October 18, 2004

[snip]

Currently, neuropsychological assessment is the most widely used instrument for neurocognitive ability and its deterioration. The introduction of imaging analysis used to differentiate which patients with mild cognitive impairment will progress to Alzheimer's and how far an Alzheimer's patient has progressed is relatively new.

Within the field of neuropsychology, there is controversy about whether this initiative's focus on imaging rather than currently used assessments will be effective.

"The way I see it, is that this is not meant to substitute [for] neuropsychological testing, but it should only be additive in terms of identifying who will progress to [Alzheimer's] and will only be beneficial to the patient," said Effie Mitsis, a neuropsychologist working with van Dyck.

[snip]

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

Saturday, October 16, 2004

Anosmia

Tomorrow's New York Times Sunday Magazine has a short piece written by someone who lost her sense of smell and her effort to try to find it once again:
Something's Off
By ROBIN MARANTZ HENIG
17 October 2004
The New York Times

[Snip]

Smell is the stepchild of the senses, the one that many think they could do without. But when I couldn't smell things, I couldn't fully inhabit the world, and my movements in it were somehow, almost imperceptibly, more clumsy. This month, when the Nobel Prize was awarded to two researchers for investigating the science of smell, it brought back my mixed feelings about my own sense of smell's protracted disappearance.

It vanished in 2002, a result of a bad fall. As my neurosurgeon explained, when my head hit the ground, my brain sloshed around, which smashed delicate nerve endings in my olfactory system. Maybe they'll repair themselves, she said (in what struck me as much too casual a tone), and maybe they won't. If I had to lose something, it might as well have been smell; at least nothing about my personality or my memory had changed, as can happen with head trauma. So it seemed almost churlish to feel, as the months went on, so devastated by this particular loss.

But I was heartbroken. My sense of smell was always something I took pleasure in. I could tell, by smelling him, if Jeff was troubled, excited or sad. I could fall in love with him all over again -- or with a passing stranger -- with one good whiff. And one of my favorite parts of mothering has been smelling my daughters, those deep sweet smells in the crooks of their necks and at the shaggy tops of their heads. Without scent, I felt as if I were walking around the city without my contact lenses, dealing with people while wearing earplugs, moving through something sticky and thick. The sharpness of things, their specificity, diminished.
[ ... Read the full article ...] (free registration required).

Friday, October 15, 2004

What's New In ...... Prosopagnosia?

Host G. [Prosopagnosia--incapacity to recognize faces] Lakartidningen. 2004 Aug 26;101(35):2661-2. Swedish. No abstract available. PMID: 15458222 [PubMed - indexed for MEDLINE]

Duchaine BC, Dingle K, Butterworth E, Nakayama K. Normal greeble learning in a severe case of developmental prosopagnosia. Neuron. 2004 Aug 19;43(4):469-73. PMID: 15312646 [PubMed - indexed for MEDLINE]

Hadjikhani N, Joseph RM, Snyder J, Chabris CF, Clark J, Steele S, McGrath L, Vangel M, Aharon I, Feczko E, Harris GJ, Tager-Flusberg H. Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces. Neuroimage. 2004 Jul;22(3):1141-50. PMID: 15219586 [PubMed - indexed for MEDLINE]

Larner AJ. Lewis Carroll's Humpty Dumpty: an early report of prosopagnosia? J Neurol Neurosurg Psychiatry. 2004 Jul;75(7):1063. No abstract available. PMID: 15201376 [PubMed - indexed for MEDLINE]

Yamasaki T, Taniwaki T, Tobimatsu S, Arakawa K, Kuba H, Maeda Y, Kuwabara Y, Shida K, Ohyagi Y, Yamada T, Kira J.
Electrophysiological correlates of associative visual agnosia lesioned in the ventral pathway. J Neurol Sci. 2004 Jun 15;221(1-2):53-60. PMID: 15178214 [PubMed - indexed for MEDLINE]

Garcia Garcia R, Cacho Gutierrez LJ. [Prosopagnosia: is it a single or a multiple entity?] Rev Neurol. 2004 Apr 1-15;38(7):682-6. Review. Spanish. PMID: 15098192 [PubMed - indexed for MEDLINE]

Duchaine BC, Nakayama K. Developmental prosopagnosia and the Benton Facial Recognition Test. Neurology. 2004 Apr 13;62(7):1219-20. PMID: 15079032 [PubMed - indexed for MEDLINE]

Kilgour AR, de Gelder B, Lederman SJ. Haptic face recognition and prosopagnosia. Neuropsychologia. 2004;42(6):707-12. PMID: 15037050 [PubMed - indexed for MEDLINE]

Kobayashi K. [Progressive prosopagnosia associated with selective right temporal lobe atrophy] Nippon Rinsho. 2004 Jan;62 Suppl:171-4. Review. Japanese. No abstract available. PMID: 15011343 [PubMed - indexed for MEDLINE]

Snowden JS, Thompson JC, Neary D. Knowledge of famous faces and names in semantic dementia. Brain. 2004 Apr;127(Pt 4):860-72. Epub 2004 Feb 25. PMID: 14985259 [PubMed - indexed for MEDLINE]

Thursday, October 14, 2004

Imaging Alzheimer Disease

From a press release by the National Institute on Aging:
National Institute on Aging, Industry Launch Partnership, 60 Million Dollar Alzheimer’s Disease Neuroimaging Initiative
  
Wednesday, October 13, 2004, 10 a.m. ET

Contact:   Vicky Cahan
               Doug Dollemore
               (301) 496-1752

The National Institute on Aging (NIA) in conjunction with other Federal agencies, private companies and organizations today launched a $60 million, 5-year public-private partnership—the Alzheimer’s Disease Neuroimaging Initiative—to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s disease (AD).

The study could help researchers and clinicians develop new treatments and monitor their effectiveness as well as lessen the time and cost of clinical trials. The project is the most comprehensive effort to date to find neuroimaging and other biomarkers for the cognitive changes associated with MCI and AD.
[snip]

“This is an extraordinary pooling of talent and resources toward a common goal—delaying or preventing Alzheimer’s disease,” says Richard J. Hodes, M.D., Director of the NIA. “The initiative should become a landmark study in the development of neuroimaging and other biomarkers, helping us to find biological changes early so that we can identify the people at highest risk of the disease and test the effectiveness of new therapies more quickly and efficiently.”

The study will take place at approximately 50 sites across the U.S. and Canada.  In April 2005, investigators will begin recruiting about 800 adults, ages 55 to 90, to participate in the research—approximately 200 cognitively normal older individuals to be followed for 3 years, 400 people with MCI to be followed for 3 years, and 200 people with early AD to be followed for 2 years.

The study will compare neuroimaging, biological, and clinical information from these participants, seeking correlations among the data that will track the progression of memory loss from its earliest stages. Neuroimaging research has suggested that PET or MRI may serve as a more sensitive and consistent measure of disease progression than the neuropsychological and cognitive assessments now typically used in research and clinical practice. As MCI and AD progress, for example, areas of the brain involved with memory, such as the hippocampus (a part of the brain heavily involved in memory), shrink.

Using the high resolution images produced by MRI, researchers will evaluate the best ways of measuring this volume loss in the hippocampus and other brain structures. PET scans assess brain function by measuring the rate of metabolism of glucose, the brain’s fuel. PET scans of people with AD show that glucose in certain parts of the brain is metabolized at lower levels than in healthy people, and previous studies have shown that low glucose metabolism can be seen in some people even before noticeable symptoms of memory loss occur. The Initiative will seek to identify additional biological factors from blood, cerebrospinal fluid (CSF), and urine samples.
[ ... Read the full press release ... ]

Wednesday, October 13, 2004

MS Individuals Using Segways

The New York Times provides an interesting feature piece in its Circuits section tomorrow about the use of the Segway Human Transporter by individuals with various disabilities. It should also be noted that the creator of the Segway has developed a less-well-known wheelchair that can raise a person closer to eye level than a standard wheelchair and that can climb stairs.
Oft-Scorned Segway Finds Friends Among the Disabled
By RACHEL METZ
Published: October 14, 2004

WHIRRING quietly down the sidewalk on East 42nd Street and into a Starbucks one recent afternoon, Chandler Hovey drew looks and comments from passers-by.

What was most eye-catching was his means of transport: the Segway Human Transporter, a two-wheeled, gyroscopically balanced electric scooter. What was less evident, except to those close enough to spot the blue handicapped symbol on his scooter, was that he is disabled.

Mr. Hovey, 63, a money manager, has multiple sclerosis. For almost 18 months, his Segway has regularly transported him the roughly 30 blocks from his home to his office. When he is not using the Segway to dart around Manhattan, Mr. Hovey uses a cane, which he hangs on the scooter's handlebars, to help him maneuver around daily obstacles. But on the Segway, he appears as able-bodied as those he is passing by.

"Instead of being at fire hydrant height, you're at human being height," he said of many users. Several hundred people nationwide are using Segways to cope with disabilities like scoliosis and arthritis and even missing limbs, according to a group called Disability Rights Advocates for Technology, or Draft, which is promoting such use. Like Mr. Hovey, many have disabilities serious enough to require assistance with walking, but not a wheelchair.

The Segway, which has been generally available since early last year, is not approved (or marketed) for use as a medical device. And it has drawn opposition and even legislation in some cities over concern that its use on sidewalks endangers pedestrians. But that has not deterred disabled riders willing to pay $3,000 or more - a cost not usually covered by medical insurance.

Leonard Timm, an above-the-knees double amputee and a co-founder of Draft, said his group estimated the ranks of disabled Segway users nationwide at 400 to 600. Often, he said, they are using the Segway along with another device, like a cane, wheelchair or a sit-down power scooter.

Mr. Timm modified his Segway to incorporate a wooden seat he built that enables him to sit while riding. He is working on a new aluminum seat.

Disabled Segway riders cite health benefits like improved digestion and circulation. While their overall energy might not improve, some say they can now concentrate their efforts on things other than struggling to walk.
[ ... Read the full article ... ]

Rehabilitation Trends: Decreased Length of Stay and Mortality

Usually, the weekly online issue of the Journal of the American Medical Association includes the full text of one of its articles available on a free-access basis. Today's new issue has as its "free access" choice a report on trends in rehabilitation care: [access the article here]. A .pdf version is also available at the access page.

Here is the paper's abstract:
Kenneth J. Ottenbacher, PhD, OTR; Pam M. Smith, DNS, RN; Sandra B. Illig, MS, RN; Richard T. Linn, PhD; Glenn V. Ostir, PhD; Carl V. Granger, MD. Trends in Length of Stay, Living Setting, Functional Outcome, and Mortality Following Medical Rehabilitation. JAMA. 2004; 292: 1687-1695.

Context.  Changes in reimbursement have reduced length of stay (LOS) for patients receiving inpatient medical rehabilitation. The impact of decreased LOS on functional status, living setting, and mortality is not known.

Objective.  To examine changes in LOS, functional status, living setting, and mortality in patients completing inpatient rehabilitation.

Design.  Retrospective cohort study from 1994 through 2001 using information submitted to the Uniform Data System for Medical Rehabilitation.

Setting and Participants.  Data were analyzed from 744 inpatient medical rehabilitation hospitals and centers located in 48 US states. A total of 148 807 patient records from 5 impairment groups (stroke, brain dysfunction, spinal cord dysfunction, other neurologic conditions, and orthopedic conditions) were examined. Patients’ mean age was 67.8 (SD, 15.8) years; the sample was 59% female and 81% non-Hispanic white.

Main Outcome Measures.  Discharge setting, follow-up living setting, change in functional status, and mortality.

Results.  Median LOS decreased from 20 to 12 days (P less than .001) from 1994 to 2001. The proportional decrease in median LOS was greatest (42%) for patients with orthopedic conditions. Mean days to follow-up remained constant from 89 in 1994 to 90 in 2001. Functional status was clinically stable, while efficiency (functional status change divided by LOS) increased significantly (P less than .001). Rates of discharge to home and living at home at follow-up remained stable, ranging from 81% to 93%. However, mortality at 80- to 180-day follow-up increased from less than 1% in 1994 to 4.7% in 2001.

Conclusions.  Length of stay for inpatient rehabilitation decreased substantially from 1994 to 2001. Effectiveness as measured by change in functional status did not change clinically, and living setting did not change. Efficiency for functional outcomes improved but mortality at follow-up increased.

Medical Informatics: Implantable RF Microchips

The Washington Post reports on the approval by the FDA of the use of implantable radio-frequency microchips for medical information applications. As the article suggests, some neurological patients may fall within the targeted applications of this product.
FDA Approves Implantable Chip for Medical Records
By Diedtra Henderson
AP Science Writer
Wednesday, October 13, 2004; 2:05 PM

WASHINGTON (AP) -- The Food and Drug Administration on Wednesday approved an implantable computer chip that can pass a patient's medical details to doctors, speeding care.

VeriChips, radio frequency microchips the size of a grain of rice, have already been used to identify wayward pets and livestock. And nearly 200 people working in Mexico's attorney general's office have been implanted with chips to access secure areas containing sensitive documents.

Delray Beach, Fla.-based Applied Digital Solutions said it would give away $650 scanners to roughly 200 trauma centers around the nation to help speed its entry into the health care market.

A company spokesman would not say how much implanting chips would cost for humans, even though chips have been implanted in some, including Scott R. Silverman, the company's chief executive officer.

The company is targeting patients with diabetes, chronic cardiac conditions, Alzheimer's disease and those who undergo complex treatments like chemotherapy, said Dr. Richard Seelig, Applied Digital Solutions' vice president of medical applications.
[snip]
With the pinch of a syringe, the microchip is inserted under the skin in a procedure that takes less than 20 minutes and leaves no stitches.

Silently and invisibly, the dormant chip stores a code -- similar to the identifying UPC code on products sold in retail stores -- that releases patient-specific information when a scanner passes over the chip.

At the doctor's office those codes stamped onto chips, once scanned, would reveal such information as a patient's allergies and prior treatments.
[ ... Read the full article ... ] (free registration required)

Bilingualism and the Brain

A new study about the relation between the brain and bilinualism, as presented in a Reuters news report:
Learning 2nd Language Changes Brain Anatomy - Study
Wed 13 October, 2004 19:18
By Patricia Reaney
LONDON (Reuters) - Being bilingual produces changes in the anatomy of the brain, scientists said on Wednesday in finding that could explain why children are so much better than adults at mastering a second language.

They found that people who speak two languages have more gray matter in the language region of the brain. The earlier they learned the language, the larger the gray area.

"The gray matter in this region increases in bilinguals relative to monolinguals -- this is particularly true in early bilinguals who learned a second language early in life," said Andrea Mechelli, a neuroscientist at University College London.

"The degree is correlated with the proficiency achieved."

Learning another language after 35 years old also alters the brain but the change is not as pronounced as in early learners.

"It reinforces the idea that it is better to learn early rather than late because the brain is more capable of adjusting or accommodating new languages by changing structurally," Mechelli said.

"This ability of the brain decreases with time."

Mechelli and his team used structural brain imaging to compare the size of the gray matter in the brains of 25 monolinguals, 25 early bilinguals who learned a second language before the age of five and 33 late bilinguals.

All the volunteers in the study, which is described in the science journal Nature, were native English speakers of comparable age and education.

In the bilinguals, the gray matter in the left inferior parietal cortex was larger than in the monolinguals or the bilinguals who picked up the second language between the ages of 10-15.

"By looking at the size of the change (in the brain) I can tell whether someone is very proficient or not because the bigger the change the better the proficiency," said Mechelli.

Grey matter in the brain is made up of neurons, or brain cells. The scientists do not know whether the change in bilinguals means there is an increase in the size of the cells, the number of cells or the connections between them.

"The next step would be to understand the change better at a small-scale level," according to Mechelli.

He and his colleagues are planning further studies with people who have difficulty learning languages to see whether their brain behaves differently.

They also plan to study speakers of several languages to determine whether the increase in gray matter is proportional to the number of languages they have mastered.
[ ... Read the full report ... ]

Tuesday, October 12, 2004

Deep Brain Stimulation and Tourette's Syndrome

Over the past few months, there have been a number of stories in the media about the topic of deep brain stimulation and its possible applications in the near future. The following article comes from Canada’s Globe and Mail:
Surgery helps short-circuit Tourette's syndrome
By PAUL TAYLOR
From Tuesday's Globe and Mail

Jeff Matovic used to eat with a plastic spoon to prevent himself from accidentally gouging out one of his eyes.The 31-year-old has Tourette's syndrome, a neurological disorder characterized by involuntary muscle movements. Mr. Matovic, who developed symptoms at age 3, could not sit, walk or even sleep without his body exploding in an endless series of jerking motions and verbal outbursts. He has broken glasses in his bare hands and dented walls with his head because of sudden muscle contractions.

Things got so bad, Mr. Matovic sought out doctors who would implant electrodes in his brain to quiet his restless body, after hearing about another patient who had the treatment. The operation took place six months ago at the University Hospitals of Cleveland, and his body has been calm ever since.

"It's just amazing. It is truly phenomenal," Mr. Matovic said in a telephone interview from his home in a Cleveland suburb. Before the operation, he could barely talk on a phone because of an irrepressible urge to clear his throat, grunt and hiss -- not to mention the difficulty of holding the receiver.

Mr. Matovic underwent a treatment known as deep-brain stimulation, increasingly used to treat a wide range of brain disorders. Much like a heart pacemaker, the treatment provides a stream of electrical current to counteract a part of the brain that is misbehaving.

During surgery, electrodes are inserted into specific spots in the brain. They are then connected through wires under the skin (beneath the scalp, neck and upper chest) to a replaceable battery unit implanted beneath the collarbone.

Only a handful of people (none in Canada) has received the treatment for Tourette's. But deep-brain stimulation has been used for more than a decade to treat other movement disorders, such as Parkinson's disease, tremors and dystonia, which distorts posture. About 30,000 people around the world now have such brain implants.

As neurosurgeons refine their skills, medical experts speculate that deep-brain stimulation could be used to treat everything from drug addictions to depression. Studies are under way at various medical institutions to expand its use. The technique is proving effective partly because the brain itself operates like an electrical circuit. When even just a few brain cells are misfiring, they can cause widespread problems resulting in either a physical or mental disorder.

A little electrical current, applied in the right place, seems to restore harmony to the discordant symphony of the disordered brain, said Dr. Robert Maciunas, the neurosurgeon who operated on Mr. Matovic.
[ ... Read the full article ...]

ACE Inhibitors and Alzheimer Disease

A press release from the American Academy of Neurology about a research paper published in the new issue of Neurology:
Blood Pressure Drugs May Slow Deterioration of Alzheimer’s
11 October 2004
Newswise — Certain blood pressure drugs may slow the deterioration of Alzheimer’s disease, according to a study published in the October 12 issue of Neurology, the scientific journal of the American Academy of Neurology.

Called angiotensin-converting enzyme inhibitors, or ACE inhibitors, the drugs are used to treat high blood pressure. Only ACE inhibitors that can penetrate the blood-brain barrier were shown to have the effect on Alzheimer’s. The blood-brain barrier is a natural protective mechanism that shields the brain from foreign substances.

The study involved 162 people in Japan living in long-term care facilities with mild to moderate Alzheimer’s disease and high blood pressure. The participants were divided into three groups. For one year, each group received either a brain-penetrating ACE inhibitor, a non-brain-penetrating ACE inhibitor, or another type of blood pressure drug, called a calcium channel blocker. Those in the brain-penetrating ACE inhibitor groups received one of two drugs – perindopril or captopril.

The participants’ thinking and memory skills were tested at the beginning of the study and again at the end. The thinking and memory skills of those who took the brain-penetrating ACE inhibitors declined only slightly over the year. The skills of those who took the other drugs declined significantly.

At the beginning of the study, the participants had an average score of about 20 on the exam. The scores of those on brain-penetrating ACE inhibitors declined by an average of .6 points. The scores of those on non-brain-penetrating ACE inhibitors declined by an average of 4.6 points. The average decline was 4.9 points for those on calcium channel blockers.

“These brain-penetrating ACE inhibitors might have benefits not only for the prevention but also for the treatment of mild to moderate Alzheimer’s,” said study author Takashi Ohrui, MD, of Tohoku University School of Medicine in Sendai, Japan.

“These findings are provocative and exciting, but the results must be replicated in carefully controlled, randomized, blinded studies,” said neurologist David Knopman, MD, of the Mayo Clinic in Rochester, Minn., who wrote a commentary on the study.

Knopman noted that the study has several limitations. The participants knew which drug they received, and the researchers were not blinded to which participants received which drug. Blind studies are considered more scientifically accurate, because bias cannot be introduced. Another weakness is that there is no way to tell whether one of the brain-penetrating ACE inhibitors was more effective than the other in slowing the effects of Alzheimer’s disease, Knopman said.
[ ... Read the full press release ... ]

Monday, October 11, 2004

Upcoming Event: Philadelphia, November 2004

A symposium in the field of study for which two researchers (Drs. Richard Axel and Linda Buck) were awarded the Nobel Prize for Medicine last week will be held on the 8th of November in Philadelphia. The symposium is sponsored by the University of Pennsylvania Smell and Taste Center, which was the first specialty academic center established for the study of clinical smell and taste disorders, directed by Richard Doty, Ph.D.

THE UNIVERSITY OF PENNSYLVANIA
ANOSMIA SYMPOSIUM
 
Sponsored by the University of Pennsylvania Smell and Taste Center
& Department of Otorhinolaryngology: Head and Neck Surgery*  

Monday, November 8, 2004 

Surgical Seminar Room, White Building 1 (near front entrance of hospital), Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 

*Supported by an unrestricted educational grant from Matrixx Initiatives, Inc., Phoenix, AZ 

ABOUT THE SYMPOSIUM 

Anosmia is not inconsequential, dramatically altering the flavor of foods and beverages and exposing patients to danger from spoiled foods, leaking natural gas, fire, and other environmental hazards. This symposium, the first ever devoted solely to this topic, brings together a collection of the world’s experts for a day-long event to better understand anosmia and its consequences. 

SCHEDULE AND SPEAKERS 

8:30-9:15 -- INTRODUCTION: ANOSMIA AND ITS CAUSES -- Richard L. Doty, Ph.D., Director, Smell and Taste Center, and Professor, Department of Otolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia  

9:15-9:45 -- ANATOMY OF OLFACTION & THE HUMAN NASAL PASSAGES -- James Palmer, M.D., Assistant Professor, Department of Otolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia 

9:45-10:30 -- NASAL PATENCY AND THE DYNAMICS OF NASAL AIRFLOW -- Richard E. Frye, M.D., Ph.D., Clinical Fellow, Department of Neurology, Children’s Hospital, Boston 

10:30-10:45 – Coffee Break 

10:45-11:30 -- REGENERATION IN THE OLFACTORY PATHWAYS -- James Schwob, M.D., Ph.D., Professor & Chair, Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston 

11:30-12:15 -- STRUCTURAL AND FUNCTIONAL IMAGING OF THE DYSFUNCTIONAL OLFACTORY SYSTEM -- David M. Yousem, M.D., Professor, Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore 

12:15 – 1:30 – Lunch at the University of Pennsyl-vania Museum of Archaeology and Anthropology 

1:30-2:15 -- EPIDEMIOLOGY OF ANOSMIA -- Judith Jones, M.D., Ph.D., The Degge Group, Ltd., Arlington, VA  

2:15-3:00 -- EXPERIMENTAL MODELS OF ANOSMIA IN RODENTS -- Burt Slotnick, Ph.D., Professor, University of South Florida, Tampa, FL 

3:00-3:15 -- CLOSING REMARKS -- Bert W. O’Malley, Jr., M.D., Gabriel Tucker Professor and Chair, Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania 

REGISTRATION 

All attendees must register in advance. Please RSVP by October 28th whether you will be attending. Since space is limited to 100 persons, early registration is critical to ensure acceptance. Please indicate your preference for meat or fish at the museum luncheon. 

RSVP information -- Attn: Ms. Bonnie Rosen, Events Coordinator, Department of Otorhinolaryngology: Head and Neck Surgery, 5 Ravdin Pavilion, 3400 Spruce Street, Philadelphia, PA 19104. 

Phone: 215-662-2137; FAX: 215-662-4515; bonnie.rosen@uphs.upenn.edu

Information supplied by Dr. Richard Doty of the University of Pennsylvania

Friday, October 08, 2004

Upcoming Event: New Orleans, December 2004

The Annual Tulane University Health Sciences Center (TUHSC) Brain & Behavior Symposium will be held in New Orleans, LA on the 10th and 11th of December 2004. The topic of this year's event is "Traumatic Brain Injury Revisited." The symposium will be held at the Hotel Intercontinental.

The Symposium will include both presentations and small group workshops relating to the above topics. CE credits for psychologists, physicians, and allied health professionals will be provided. For further information, contact the Center for Continuing Education at TUHSC (cme@tulane.edu).

Information supplied by Dr. F. William Black of TUHSC

In The Weeklies

Here are some relevant highlights from this week’s major scientific and medical weeklies:

New England Journal of Medicine
07 October 2004

This week’s issue includes the research report, Protected Carotid-Artery Stenting versus Endarterectomy in High-Risk Patients by Yadav and colleagues. Here is the abstract:
Background. Carotid endarterectomy is more effective than medical management in the prevention of stroke in patients with severe symptomatic or asymptomatic atherosclerotic carotid-artery stenosis. Stenting with the use of an emboli-protection device is a less invasive revascularization strategy than endarterectomy in carotid-artery disease.

Methods. We conducted a randomized trial comparing carotid-artery stenting with the use of an emboli-protection device to endarterectomy in 334 patients with coexisting conditions that potentially increased the risk posed by endarterectomy and who had either a symptomatic carotid-artery stenosis of at least 50 percent of the luminal diameter or an asymptomatic stenosis of at least 80 percent. The primary end point of the study was the cumulative incidence of a major cardiovascular event at 1 year — a composite of death, stroke, or myocardial infarction within 30 days after the intervention or death or ipsilateral stroke between 31 days and 1 year. The study was designed to test the hypothesis that the less invasive strategy, stenting, was not inferior to endarterectomy.

Results. The primary end point occurred in 20 patients randomly assigned to undergo carotid-artery stenting with an emboli-protection device (cumulative incidence, 12.2 percent) and in 32 patients randomly assigned to undergo endarterectomy (cumulative incidence, 20.1 percent; absolute difference, –7.9 percentage points; 95 percent confidence interval, –16.4 to 0.7 percentage points; P=0.004 for noninferiority, and P=0.053 for superiority). At one year, carotid revascularization was repeated in fewer patients who had received stents than in those who had undergone endarterectomy (cumulative incidence, 0.6 percent vs. 4.3 percent; P=0.04).

Conclusions. Among patients with severe carotid-artery stenosis and coexisting conditions, carotid stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy.

Lancet
09 October 2004

This week’s issue include the primary research paper mentioned in an earlier posting about the use of steroids in the acute medical management of traumatic brain injury: Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial by the CRASH trial collaborators. The issue also includes commentary and talking points about the research study.

Nature
07 October 2004

This issue includes the letter, Role for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory by Miguel Remondes and Erin M. Schuman, the first paragraph of which reads:

A dialogue between the hippocampus and the neocortex is thought to underlie the formation, consolidation and retrieval of episodic memories, although the nature of this cortico-hippocampal communication is poorly understood. Using selective electrolytic lesions in rats, here we examined the role of the direct entorhinal projection (temporoammonic, TA) to the hippocampal area CA1 in short-term (24 hours) and long-term (four weeks) spatial memory in the Morris water maze. When short-term memory was examined, both sham- and TA-lesioned animals showed a significant preference for the target quadrant. When re-tested four weeks later, sham-lesioned animals exhibited long-term memory; in contrast, the TA-lesioned animals no longer showed target quadrant preference. Many long-lasting memories require a process called consolidation, which involves the exchange of information between the cortex and hippocampus. The disruption of long-term memory by the TA lesion could reflect a requirement for TA input during either the acquisition or consolidation of long-term memory. To distinguish between these possibilities, we trained animals, verified their spatial memory 24 hours later, and then subjected trained animals to TA lesions. TA-lesioned animals still exhibited a deficit in long-term memory, indicating a disruption of consolidation. Animals in which the TA lesion was delayed by three weeks, however, showed a significant preference for the target quadrant, indicating that the memory had already been adequately consolidated at the time of the delayed lesion. These results indicate that, after learning, ongoing cortical input conveyed by the TA path is required to consolidate long-term spatial memory.

Thursday, October 07, 2004

Brain Injury: Acute Management With Steroids

Research reported in the new issue of Lancet about steroid treatment in the acute management of brain injury is being reported in a number of newspapers. Here is the report in Newsday:
Study: Steroids Useless for Head Trauma
By EMMA ROSS
AP Medical Writer
October 7, 2004, 8:51 PM EDT
LONDON -- Doctors have been giving steroids to head trauma patients for more than 30 years, but the first major study of the practice has shown they are useless and may even have killed thousands of people.

Experts said the findings, published this week in The Lancet medical journal, are "a complete and alarming surprise for all."

Head trauma, usually from car crashes, violence or falls, is the leading cause of death and disability in children and young adults in the developed world, and globally second only to HIV in causing the death of people under 40. About 3 million people die each year from head trauma.

Steroids had been used for decades in head trauma patients because it was believed their anti-inflammatory effects could help bring down swelling in the brain.

However, there was never reliable evidence steroids helped in cases of severe head injury, and their use has been controversial.

In the mid-1990s, existing evidence indicated they were probably not effective. Many doctors stopped using them, but not all.

The latest study, involving hundreds of doctors in 49 countries treating more than 10,000 patients, was stopped halfway through recruitment as it became clear steroids did not help and could be harmful.

"Most clinicians expected the trial to confirm the benefits of steroids, while others suspected that the effectiveness of steroids would turn out to be small or nonexistent," said Dr. Stefan Sauerland and Dr. Marc Maegele, experts from the University of Witten-Herdecke and the University of Cologne in Germany.

"Instead of a treatment benefit or at least equality, there were actually 159 excess deaths in the steroid group," the experts wrote in an independent critique of the study. "When extrapolating the results ... to the annual incidence of severe head injuries worldwide, it is frightening to calculate how many patients might have been harmed by steroids."

Sauerland, who was not connected with the research, estimated doctors killed about 10,000 head trauma patients with steroids in the 1980s and earlier.

The study, coordinated at the London School of Hygiene and Tropical Medicine, involved 10,008 adults with severe head injuries who were randomly allocated either a steroid drip or a fake drip for 48 hours after being admitted to the emergency room.

Within two weeks, 21 percent of the patients given steroids had died, compared with 18 percent of those given the fake drug. The results were the same regardless of how quickly the treatment was administered and regardless of the type or severity of the head injury.

Dr. Philip Stieg, chair of neurological surgery at Weill Cornell Medical Center in New York, said he was not sure the study settles the question.

"They picked one dose of steroids. Would a different dose be more effective?" asked Stieg, who was not connected with the research.

It also remains to be seen whether patients getting steroids fare better in the long term from the disabling effects of the trauma, he noted.

"If the long-term one-year follow up data suggest that steroids improve morbidity, that the patient has a better neurological outcome, then physicians would reevaluate their use of steroids," he said.

However, Sauerland said it was unlikely any long-term benefit in disability reduction could outweigh the concern about the higher death rate early in treatment.

"This is a tombstone trial," Sauerland said by telephone. "It will close the issue for ever."

Dr. Ian Roberts, coordinator of the trial, said many other treatments commonly used in trauma patients also were open to question. Approaches such as hyperventilation, barbiturates and fluid resuscitation have not been proven to help, he said.

"Trauma care has really been the poor relation of medical research," he said. "Maybe there are other surprising and alarming results out there. We don't know."

Abstract of the Day: Pediatric Epilepsy

Fastenau PS, Shen J, Dunn DW, Perkins SM, Hermann BP, Austin JK. Neuropsychological predictors of academic underachievement in pediatric epilepsy: Moderating roles of demographic, seizure, and psychosocial variables. Epilepsia. 2004 Oct; 45(10): 1261-72.

Department of Psychology, Purdue School of Science, Indiana University Purdue University Indianapolis (IUPUI), Indianapolis, Indiana, U.S.A.

Summary: Purpose: Academic underachievement is common in pediatric epilepsy. Attempts to identify seizure and psychosocial risk factors for underachievement have yielded inconsistent findings, raising the possibility that seizure and psychosocial variables play a complex role in combination with other variables such as neuropsychological functioning. This study cross-validated a neuropsychological measurement model for childhood epilepsy, examined the relation between neuropsychological functioning and academic achievement, and tested the degree to which demographic, seizure, and psychosocial variables moderate that relation. Methods: Children with chronic epilepsy (N = 173; ages 8 to 15 years; 49% girls; 91% white/non-Hispanic; 79% one seizure type; 79% taking one medication; 69% with active seizures) completed a comprehensive neuropsychological battery. Children diagnosed with mental retardation were excluded. Results: Structural equation modeling identified a three-factor measurement model of neuropsychological function: Verbal/Memory/Executive (VME), Rapid Naming/Working Memory (RN/WM), and Psychomotor (PM). VME and RN/WM were strongly related to reading, math, and writing; PM predicted writing only. Family environment moderated the impact of neuropsychological deficits on writing (p lt or = 0.01) and possibly for reading (p = 0.05); neuropsychological deficits had a smaller impact on achievement for children in supportive/organized homes compared with children in unsupportive/disorganized homes. Conclusions: These findings lend partial support for our theoretical model showing direct effects of neuropsychological function on achievement and the moderating role of family factors. This study suggests that a subgroup of children with epilepsy (those who have not only neuropsychological deficits but also disorganized/unsupportive home environments) are particularly at risk for adverse academic outcomes. Implications for intervention are discussed.

PMID: 15461681 [PubMed - in process]

Brain Injuries in Warfare

Last night, ABC's Nightline presented a report about head wounds in warfare: Transcript of report.

Wednesday, October 06, 2004

Memory Circuitry

This press release from the Howard Hughes Medical Institute discusses a newly published paper on memory formation in the brain:
Brain Circuit May Permit Scientists to Eavesdrop on Memory Formation
07 Oct 2004   

Howard Hughes Medical Institute researchers have identified a circuit in the brain that appears crucial in converting short-term memories into long-term memories. The circuit links the major learning-related area of the brain to another region that governs the brain's higher functions.

The studies open the way for eavesdropping on one of the central processes in learning and memory, says HHMI investigator Erin M. Schuman. She and graduate student Miguel Remondes of the California Institute of Technology published their findings in the October 7, 2004, issue of the journal Nature.

According to Schuman, the finding sheds light on a central question in learning and memory research that concerns the roles of two brain structures, the hippocampus, which is involved in memory formation, and the neocortex, which is associated with higher brain functions.

“There are two key findings required to understand the present work,” said Schuman. “First, lesions of the hippocampus prior to training can prevent the formation of some kinds of short-term memory. Second, if one delays the hippocampal lesion to days after training, one can observe that as the delay increases, the memory deficit decreases. These data suggest that the importance of the neocortex as a memory storage site increases with the lifetime of the memory. In addition, there is a clear need for the hippocampus and cortex to talk to one another.”

One candidate for the communication conduit is the temporoammonic (TA) projection, “a pathway that we have been chipping away at understanding for years,” said Schuman. “We and others had studied the physiology of this very direct connection between the two areas, but no one had directly studied this pathway's importance in learning.”

For the experiments, Remondes perfected a technique to make precise electrical lesions of the TA projection in the brains of rats. In the first set of experiments, he created the lesions in animals and then tested their ability to learn to navigate a tank full of opaque water to find a submerged platform. When the researchers tested the rats the day after the electrical lesions were made, they still recalled the platform's location. But they lost that memory four weeks after training.

“There were two possible explanations for this result,” said Schuman. “Either we had selectively impaired the process of converting short-term memories into long-term memories. Or, short-term and long-term memories are on parallel pathways, and the lesion had selectively affected the long-term memory pathway.”

So, in a second set of experiments, the researchers created the TA lesions in animals 24 hours after they had learned the position of the platform. These animals still retained short-term memory; but four weeks later they lost that memory as well. Since the lesion was made after learning, this experiment suggested that the animals had problems converting their short-term memory into a long-term memory - a process also called consolidation.”

“If this really was a process of memory consolidation, it implies that there's a window of vulnerability that will close,” said Schuman. “Thus, in the last experiment, we waited three weeks for the memory to consolidate and then made the lesion. When tested a week later, a majority of the animals remembered the platform location even though they had just received the lesion; that is, it appeared that they had already adequately consolidated the memory in the three weeks post-training prior to the lesion.

“These experiments tell us that the TA projection is an important part of the dialog between the hippocampus and the cortex that occurs after learning,” said Schuman. “Now, what is needed is an exploration of the specific firing patterns of neurons that make up the TA projection during learning and the consolidation period. It's interesting that a lot of the important activity likely takes place off-line, when the animal is removed from the direct behavioral experience.”
[ ... Read the full press release ... ]

Brain Surgery Circa The Year 960

This article from The Guardian is representative of several published today about an historical discovery being reported in the U.K:
Skull found at Anglo-Saxon site shows evidence of surgery
Martin Wainwright
Wednesday October 6, 2004
The Guardian

The history of brain surgery is being rewritten after the discovery of a skull which shows that complex operations were performed in Anglo-Saxon England.

A century before the Norman invasion of 1066, a doctor or itinerant healer was delicately removing scraps of skull from a 40-year-old Yorkshire peasant who had been whacked on the head.

It was such a skilful operation that a large depression on the man's brain was relieved and fractures in the bone healed. According to English Heritage archaeologists, the patient lived for many years after the operation, finally dying of unrelated causes.

His treatment, which also involved lifting a large patch of scalp measuring 10cm by 9cm (4in by 3.5in), was known to Greek physicians as trepanning, but had been assumed lost in the west after the fall of Rome and the loss of Alexandria's famous library. Nothing like the skull, part of a hoard of 700 skeletons unearthed at the deserted medieval village of Wharram Percy in Yorkshire, has previously been found.

Simon Mays, skeletal biologist at English Heritage's centre for archaeology, said: "This skull predates medieval written accounts of such surgery by at least 100 years. It is a world away from notions that Anglo-Saxon healers were all about spells and potions."

The patient had been savagely hit with a blunt instrument, probably a farming tool, which inflicted a severe fracture on the left side of his skull. The unknown surgeon, working around the year 960, remodelled healthy bone as well as removing broken splinters. The remaining gap in the skull later closed over with scar tissue.
[snip]
Work on the village's bones has been going on since 1990, when one of the longest and most thorough excavations in British archaeological history ended after 40 years. Many revisions of conventional history have followed earlier discoveries and analysis of remains.

The English Heritage team hopes that further evidence will explain why such a complex operation was performed on a peasant, whose status was identified by nutritional evidence and burial site. Mr Mays said: "Medical skills were largely reserved for the elite, and physicians attracted widespread cynicism because of their fees.

"The treatment handed out to Wharram's peasant doesn't square at all with our knowledge of the period. It seems most probable that the operation was performed by an itinerant healer of unusual skill, whose medical acumen was handed down through oral tradition."
[ ... Read the full article ... ]

Tuesday, October 05, 2004

Bilingual Ease or Difficulty: Brain Role

The following article appeared in the The Straits Times of Signapore today:
Bilingual skill 'linked to brain activity'
By Chang Ai-Lien

NOT all bilinguals are created equal.

New research here has uncovered differences in brain activity which separate people who have a knack for picking up a second language and others who have more of a struggle doing so.

'It's as though one group can engage their brain to help them do so more efficiently, while the other group cannot,' said Dr Michael Chee, the main researcher in the study.

'There appears to be some biological underpinning in being able to pick up a second language.'

The work - which has been published in the world-renowned Proceedings of the National Academy of Sciences - could also help point the way towards how best to teach the language laggards.

Dr Chee and colleagues from SingHealth's cognitive neuroscience laboratory collaborated with a scientist from the Institut National de la Sante et de la Recherche Medicale in France, which is comparable to the National Institutes of Health in the United States.

They tested 30 adults - high achievers who had done well throughout school. Among them, one group had also excelled in Chinese (equal bilinguals), while the other had done poorly (unequal bilinguals).

They were given a number of unfamiliar French words to remember briefly, while their brains were scanned using magnetic resonance imaging (MRI) to map the brain activity engaged in the work of short-term memory.

While both groups appeared to perform the task equally well, the MRI scans painted a different picture.

They found that as the memory demands increased, the equal bilinguals activated more prominently a region on the left lower frontal lobe of their brains called the left insula - an area believed to be involved in speech rehearsal and the temporary storage of verbal contents.

Interestingly, those in the group who achieved the highest Chinese scores were also the ones in whom this brain area worked the hardest, an indication of its impor- tance.

'It appears that the equal bilinguals process unfamiliar words in a way which helps them to incorporate the words into their long-term memory,' said Dr Chee.
[ ... Read the full article ... ]

Monday, October 04, 2004

The Nobel Nose

This year's Nobel Prize for Medicine has been announced: Press release and Nobel website page. Richard Axel and Linda Buck have been awarded the prize "for their discoveries of odorant receptors and the organization of the olfactory system."

Here is a snip from the Associated Press report, as published on the New York Times website:
Two Americans Win Nobel Prize in Medicine
By THE ASSOCIATED PRESS
STOCKHOLM, Sweden -- American researchers Richard Axel and Linda B. Buck shared the 2004 Nobel Prize in physiology or medicine on Monday for their work on the sense of smell -- showing how, for example, a person can smell a lilac in the spring and recall it in the winter.

They discovered genes that give rise to a huge variety of "receptor" proteins that sense particular odors. These proteins are found in cells in the nose, which communicate with the brain.

Axel, 58, of the Howard Hughes Medical Institute and Columbia University in New York, shared the prize with Buck, 57, of the Fred Hutchinson Cancer Research Center in Seattle.

They reported the gene discoveries jointly in 1991 and have since worked independently shedding further light on the olfactory system.

The Nobel assembly said the sense of smell "helps us detect the qualities we regard as positive. A good wine or a sun ripe wild strawberry activates a whole array of odorant receptors."

Told of his honor, Axel told Swedish public radio: "That's really marvelous, I'm so honored."

When asked if he had thought about becoming a Nobel laureate, he replied: "No, this is nothing I have been thinking about, I think about my science."

Asked what he would do first, he replied: "I'm going to have a cup of coffee."

Buck did not immediately return a call to the cancer center, but center spokeswoman Susan Edmonds said, "How wonderful! That's exciting."

Academy members tell The Associated Press that the decision to give the pair the award was not in light of any medical or commercial payoffs, but rather to honor their exploration of one of the humanity's most profound senses.

Axel and Buck clarified the intricate biological pathway from the nose to the brain that lets people sense smells. A whiff of an odor brings a mix of different molecules into the nose, where each molecule activates several odor receptors. This pattern of activation is interpreted by the brain, letting people recognize and form memories of about 10,000 different odors, the Nobel Assembly said.

Axel and Buck studied mice, which have about 1,000 odor receptor types. People have somewhat fewer. The two scientists showed that about 3 percent of human genes are devoted to producing the odor receptors.
[ ... Read the full report ... ]

Saturday, October 02, 2004

"Cosmetic Neurology" - Part 2

National Public Radio's All Things Considered aired a story yesterday on the topic of cognitive-enhancing medications which, along with the earlier Wall Street Journal report, was generated by a commentary in the current issue of Neurology.
Drug Sparks Memory-Enhancement Debate
All Things Considered, October 1, 2004
Drugs being developed to aid Alzheimer's disease sufferers promise improved memory function. But the drugs are also reported to aid the memory of healthy people. An article in the journal Neurology suggests that we may be entering an era of cosmetic neurology, when a "brain-lift" is possible. NPR's Jon Hamilton reports.
The NPR story is available in an online audio stream available here: audio stream page.

"Momemtary Autism"

Writer Malcolm Gladwell (author of The Tipping Point) gave a presentation today at The New Yorker Festival about his forthcoming release, Blink: The Power of Thinking Without Thinking, published by Little, Brown with a January 2005 release date.

The premise of his new book overlaps with neuroscience, psychology, and social psychology. What happens to our thinking and decision-making skills when an acute event locks us into an immediate choice? Using circumstances from notable police events (e.g., the 1999 shooting of Amadou Diallo or the beating of Rodney King), Gladwell describes how acute physiological reactivity (e.g., resulting in the senses of tunnel vision, reduced auditory processing, and subjective time slowing) and the immediacy of time demands (one second, two seconds) results in the acute loss of social context and in the ability to engage in so-called "mind reading" of the other person --- "...social blunders with guns..." and "instantaneous moments when things go wrong, leading to heartbreak..." is how he phrased it at times. Discussing some psychological research, he outlined the fragility of human cognitive skills in acute situations that take us from our sophisticated abilities to the momemtary autism of the moment.

His book also examines the flip side of this, which he calls "thin slicing," when intuition kicks in accurately despite the most minimum of information.

I don't know how in depth he gets with his neuroscientific source material, but it sounds like it could be a good read early in the new year.

Friday, October 01, 2004

"Cosmetic Neurology"

A Wall Street Journal writer's report, published online at sfgate.com, concerning the use of cognitively enhancing medications:
Memory drugs create new ethical minefield
SHARON BEGLEY, The Wall Street Journal
(10-01) 06:52 PDT (AP) --
Move over, botox. Although injections of the most potent natural toxin known to science are marketed as knife-free plastic surgery to reduce wrinkles, Botox treatment is actually a neurological intervention. The toxin blocks the release of a neurochemical, acetylcholine, from neurons. That makes it the opening act in what promises -- or threatens -- to be a significant new drama. Welcome to "cosmetic neurology."
[snip]
Compounds called cholinesterase inhibitors boost levels of the neurotransmitter acetylcholine, which lets neurons communicate with each other. One, donepezil (sold as Aricept), is approved for Alzheimer's disease. But that may be only one of its talents. In a 2002 study, scientists gave donepezil to one group of healthy, middle-age pilots and dummy pills to another. The donepezil group did markedly better learning maneuvers in a Cessna 172 simulator, particularly those used in flight emergencies.

Some drugs that affect memory work very selectively. So-called CREB inhibitors (CREB is a protein essential for incising memories in the brain) "seem to selectively erase only disturbing memories," says neurologist Anjan Chatterjee of the University of Pennsylvania, Philadelphia. And propanolol, a beta blocker, enhances the memory of events that are emotionally charged and that the brain otherwise suppresses. It also seems to erase the negative emotions associated with bad memories. Healthy people given the drug recall disturbing stories as if they were no more emotionally charged than a grocery list.

It's not that neuroscientists are deliberately looking for drugs that might be used for cosmetic neurology. Rather, these more frivolous uses are being discovered serendipitously, often in research on serious neurological diseases such as stroke. For instance, scientists find that small doses of amphetamines help stroke patients undergoing physical therapy relearn motor skills, such as tying shoes and using utensils, better and more quickly than with therapy alone. Taken half an hour before a therapy session, amphetamines seem to promote what's called neuroplasticity, the ability of the brain to form new connections or strengthen existing ones between its neurons. Those connections underlie both simple and complex sequences of movement.
[snip]
The day may be coming when perfectly healthy people will pop speed before a tennis lesson or piano instruction, knowing it may stimulate the brain rewiring that underlies a perfect backhand or a flawless "Fur Elise." Botox, after all, originally received government approval to treat two serious eye-muscle disorders, and now aging boomers regard a quick fix as no more momentous than a swipe of mascara. Cosmetic neurology could well follow the same arc, which means that the time for neurologists to weigh in on the ethical implications of all this is now.

Those implications are profound. If drugs can improve learning, make painful memories fade and sharpen attention, should physicians prescribe them? Must physicians prescribe them? Must patients -- perhaps pilots compelled by an employer -- take them? Might one airline distinguish itself from competitors by advertising its donepezil-taking crews?

Dr. Chatterjee captures the dilemma in a paper he wrote for the current issue of Neurology: "The distinction between therapy and enhancement can be vague, particularly when the notion of 'disease' lacks clear boundaries. ... If one purpose of medicine is to improve the quality of life of individuals who happen to be sick, then should medical knowledge be applied to those who happen to be healthy," lifting patients from normal functioning to enhanced functioning?
[ ... Read the full report ... ]

Memory Divided

The new October issue of the American Psychological Association's Monitor on Psychology includes several short articles of interest to neuroscience readers. One of these articles is about one researcher's career of researching memory systems. Here is a snip from the full article, "Memory Divided" by Deborah Smith Bailey:

Past research has shown that largely separate memory systems are involved in learning different kinds of tasks, Packard said. For example, the hippocampus is key to cognitive learning, such as spatial mapping--useful for rats remembering where to find food in a maze when they are released from a new starting point--while the caudate nucleus mediates stimulus-response or habit learning--such as simply learning to turn left in a maze to find food, regardless of the starting point.

Damaging one of these respective brain areas wipes out an animal's ability to learn specific tasks. For example, hippocampal system lesions impair spatial learning, while caudate nucleus lesions impair habit learning--findings replicated in humans and other primates.

Moreover, Packard's research has shown that injecting memory-enhancing drugs into the hippocampus can heighten performance on tasks that require cognitive memory, while boosts to the caudate nucleus improve rats' performance on habit-learning tasks.

However, said Packard, rats with hippocampal lesions actually perform better than undamaged rats on some habit-learning tasks that use the caudate nucleus. The findings suggest that the hippocampal memory system sometimes interferes with learning in the caudate nucleus.
[ ... Read the full article ... ]

In The Weeklies

Here are some relevant highlights from this week’s major scientific and medical weeklies:

New England Journal of Medicine
30 September 2004
The Images in Clinical Medicine section this week includes a piece about Communicating Hydrocephalus by Newman and Segal, which includes a free PowerPoint download of the image for teaching use.

Lancet
02 October 2004
This week’s issue includes a Talking Points piece about variant CJD and one about dementia-related clinical drug trials. It also includes the commentary, Testing for prions: A novel protocol for vCJD prevalence studies, by Glatzel.

Nature
30 September 2004
This week’s issue includes a letter on the topic of Small modulation of ongoing cortical dynamics by sensory input during natural vision by Fiser.