Tuesday, December 27, 2011

Neuropsychology Abstract of the Day: Aging and Cognition

Subjective Cognitive Complaints of Older Adults at the Population Level: An Item Response Theory Analysis
Alzheimers Disease and Associated Disorders. 2011 Dec 20;
Snitz BE, Yu L, Crane PK, Chang CC, Hughes TF, Ganguli M


Subjective cognitive complaints (SCCs) are increasingly a focus in studies on prodromal Alzheimer disease (AD) and risk for dementia. Little is known about the optimal approach to measure SCCs. We used item response theory (IRT) to examine the characteristics of 24 SCC items in a sample of 3495 older adults pooled from 4 community-based studies. We investigated the potential advantages of IRT scoring over conventional scoring on the basis of participants' item response patterns. Items most likely endorsed by individuals low in SCC severity relate to word retrieval and general subjective memory decline. Items likely endorsed only by individuals high in SCC severity relate to nonepisodic memory changes, such as decline in comprehension, judgment and executive functions, praxis and procedural memory, and social behavior changes. Above and beyond conventional total score, IRT scoring of SCCs was associated with performance on objective cognitive tests, and was associated with cognitive test performance among participants endorsing only 1 SCC item. Thus, IRT scoring captures additional information beyond a simple sum of SCC symptoms. Modern psychometric approaches including IRT may be useful in developing: (1) brief community screening questionnaires; and (2) more sensitive measures of very subtle subjective decline for use in prodromal Alzheimer disease research.

PMID: 22193355 [PubMed - as supplied by publisher]

Friday, December 23, 2011

Clinical Trials in England

The BBC's "Newspod" podcast from the 22nd of December includes an item looking at contemporary issues in performing pharma clinical trials in England. Comparison is made to what is considered to be the more-successful Scotland model.

Approx 7 minutes into the podcast; lasting several minutes.

University of Iowa College of Law to Hold Colloquium on Aging Population

UI College of Law to hold colloquium on aging population
5:23 PM, Dec. 21, 2011


"The 13 weekly sessions start Jan. 12 and will be available online to the public through live-streaming and podcasts, law professor and organizer Josephine Gittler said. Nationally-recognized experts in the field of public policy and aging, including Charles Sabatino, director of the American Bar Association’s Commission on Law and Aging; Robert Egge, vice president of public policy and advocacy for the Alzheimer’s Association, and Daniel Marson, director of the Alzheimer’s Disease Center at the University of Alabama at Birmingham, will attend some of the sessions."


Read the full article

Thursday, December 22, 2011

It's a Free Download!

Executive deficits are related to the inferior frontal junction in early dementia
Brain. 2011 Dec 19;
Schroeter ML, Vogt B, Frisch S, Becker G, Barthel H, Mueller K, Villringer A, Sabri O

Access article here

Tuesday, December 20, 2011

Neuropsychology Abstract of the Day: Alzheimer's Disease Progression

Measuring Alzheimer disease progression with transition probabilities: Estimates from NACC-UDS
Curr Alzheimer Res. 2011 Nov 28;
Spackman DE, Kadiyala S, Neumann PJ, Veenstra DL, Sullivan SD


Objectives: Estimate the probabilities, for Alzheimer's disease (AD) patients, of transitioning between stages of disease severity (mild, moderate, severe, dead) and care settings (community, institutional). Methods: Data were compiled by the National Alzheimer Coordinating Center. The main analyses were limited to 3,852 patients who were >50 years old, diagnosed with possible/probable AD and had at least two center visits. A multinomial logistic model accounting for patient and center level correlation was used to calculate transition probabilities between stages of the Clinical Dementia Rating (CDR). Separately we calculated the probabilities of being institutionalized based on CDR stage. Both analyses controlled for baseline age, time between visits, sex, marital status, whether white, whether Hispanic and number of years of education. Results: The annual probabilities of dying for patients in mild, moderate and severe health states were 5.5%, 21.5% and 48.0%, respectively, while the annual probabilities for institutionalization were 1.2%, 3.4% and 6.6%, respectively. The majority of mild and moderate patients remain in the same health state after one year, 77.4% and 50.1% respectively. Progressing patients are most likely to transition one stage, but 1.3% of mild patients become severe in one year. Some patients revert to lower severity stages, 7% from moderate to mild. Conclusions: Transition probabilities to higher CDR stages and to institutionalization are lower than those published previously, but the probability of death is higher. These results are useful for understanding AD progression and can be used in simulation models to evaluate costs and compare new treatments or policies.

PMID: 22175655 [PubMed - as supplied by publisher]

Monday, December 19, 2011

Neuropsychology Abstract of the Day: Epilepsy

The cognitive impact of antiepileptic drugs
Ther Adv Neurol Disord. 2011 Nov; 4(6): 385-407
Eddy CM, Rickards HE, Cavanna AE


Effective treatment of epilepsy depends on medication compliance across a lifetime, and studies indicate that drug tolerability is a significant limiting factor in medication maintenance. Available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. On the other hand, some agents may serve to enhance cognitive function. In this review paper, we highlight the range of effects on cognition linked to a variety of newer and older AEDs, encompassing key alterations in both specific executive abilities and broader neuropsychological functions. Importantly, the data reviewed suggest that the effects exerted by an AED could vary depending on both patient characteristics and drug-related variables. However, there are considerable difficulties in evaluating the available evidence. Many studies have failed to investigate the influence of patient and treatment variables on cognitive functioning. Other difficulties include variation across studies in relation to design, treatment group and assessment tools, poor reporting of methodology and poor specification of the cognitive abilities assessed. Focused and rigorous experimental designs including a range of cognitive measures assessing more precisely defined abilities are needed to fill the gaps in our knowledge and follow up reported patterns in the literature. Longitudinal studies are needed to improve our understanding of the influence of factors such as age, tolerance and the stability of cognitive effects. Future trials comparing the effects of commonly prescribed agents across patient subgroups will offer critical insight into the role of patient characteristics in determining the cognitive impact of particular AEDs.

PMID: 22164192 [PubMed - in process]

Sunday, December 18, 2011

Neuropsychology Abstract of the Day: Sports-Related Concussion

Role of Neuropsychologists in the Evaluation and Management of Sport-related Concussion: An Inter-Organization Position Statement
Clin Neuropsychol. 2011 Nov; 25(8): 1289-1294
Echemendia RJ, Iverson GL, McCrea M, Broshek DK, Gioia GA, Sautter SW, Macciocchi SN, Barr WB


Over the past 20 years, clinical neuropsychologists have been at the forefront of both scientific and clinical initiatives aimed at developing evidence-based approaches to the evaluation and management of sport-related concussion. These efforts have directly impacted current policy on strategies for injury assessment and return-to-play by athletes after concussion. Many states are considering legislation requiring (a) education of athletes, parents, coaches, and school/organization officials on the recognition, evaluation, and management of sport-related concussions; (b) removal from play of any youth athlete that is suspected of having sustained a concussion; and (c) not allowing the student to return to participation until the student is evaluated and cleared for return to participation in writing by an appropriate healthcare professional. It is the official position of the American Academy of Clinical Neuropsychology (AACN), American Board of Neuropsychology (ABN), Division 40 (Neuropsychology) of the American Psychological Association (APA), and the National Academy of Neuropsychology (NAN) that neuropsychologists should be included among the licensed health care professionals authorized to evaluate, clinically manage, and provide return to play clearance for athletes who sustain a sport-related concussion.

PMID: 22171535 [PubMed - in process]

From MindHacks: The Pavement Dance!

From the MindHacks blog, with a link to the piece in The Economist:

The crowd dynamics of the city safari
18 December 2011
Read the blog post

Tuesday, December 13, 2011

From Pharmalot: Informed Consent Form Readibility

An interesting read. I always aimed for 6th-grade reading level myself, so it surprised me to read of this finding:

Informed Consent Forms Target 11th Grade Readers
By Ed Silverman
December 12th, 2011 // 9:29 am
Read the full blog post

Friday, December 09, 2011

Vegetative States

From last Sunday's New York Times Sunday Magazine:

A Drug That Wakes the Near Dead
04 December 2011

"A surprising drug has brought a kind of consciousness to patients once considered vegetative — and changed the debate over pulling the plug."

Read the article

Thursday, December 08, 2011

Neuropsychology Abstract of the Day: Orbitofrontal Cortex

Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values
Annals of the New York Academy of Science. 2011 Dec; 1239(1): 1-13
Rudebeck PH, Murray EA


The primate orbitofrontal cortex (OFC) is often treated as a single entity, but architectonic and connectional neuroanatomy indicate that it has distinguishable parts. Nevertheless, few studies have attempted to dissociate the functions of its subregions. Here we review findings from recent neuropsychological and neurophysiological studies that do so. The lateral OFC seems to be important for learning, representing, and updating specific object-reward associations. The medial OFC seems to be important for value comparisons and choosing among objects on that basis. Rather than viewing this dissociation of function in terms of learning versus choosing, however, we suggest that it reflects the distinction between contrasts and comparisons: differences versus similarities. Making use of high-dimensional representations that arise from the convergence of several sensory modalities, the lateral OFC encodes contrasts among outcomes. The medial OFC reduces these contrasting representations of value to a single dimension, a common currency, in order to compare alternative choices.

PMID: 22145870 [PubMed - in process]

Wednesday, December 07, 2011

From the In The Pipeline Blog: Novartis and Neuroscience

Read the In The Pipeline blog entry (06 December 2011).

Clinical Trials: Solanezumab in Alzheimer's Disease

From Bloomberg:

Eli Lilly Shares Rise on Alzheimer’s Drug Hopes
By Drew Armstrong and Robert Langreth
Dec 6, 2011


"Solanezumab is an antibody designed to clear protein fragments called beta amyloid that clutter the brains of patients with Alzheimer’s disease. Pfizer Inc. (PFE), Johnson & Johnson and Elan are testing bapineuzumab, a similar drug."


Read the article

Tuesday, December 06, 2011

Clinical Trials: EVP-6124 Phase 2b Clinical Trial in Schizophrenia

From Drug Discovery & Development:

Positive Study Results for Schizophrenia Drug
Drug Discovery & Development
December 05, 2011

"EnVivo Pharmaceuticals announced the analysis of a completed Phase 2b clinical trial of EVP-6124, a novel, orally bioavailable nicotinic alpha-7 agonist, in schizophrenia."

Read the full report

Neuropsychology Abstract of the Week: First-Person Narrative

Narrative accounts like this are not common, but still excellent reading for students of neuropsychology:

A Mind "Surrounded by a Moat": A First-person Account of Cognitive Impairment in Multiple Sclerosis
Cogn Behav Neurol. 2011 Nov 29;
Anonymous , Stern EB


This is a first-person account of the cognitive impairments-in speaking, writing, and thinking-caused by multiple sclerosis in a professional writer. The patient explains how she has worked around her deficits in rebuilding her life over the 18 years since her diagnosis. Her personal account is woven together with her clinical history, including her neuropsychological testing and magnetic resonance imaging results. A companion article giving perspectives on the case was written by a cognitive neuroscientist who has been studying some of the types of deficits reported by the patient.

PMID: 22134193 [PubMed - as supplied by publisher]

Friday, December 02, 2011

Congratulations Dr. Patricia Kuhl!

The 20th Jean-Louis Signoret Neuropsychology Prize of the Fondation Ipsen is Awarded to Prof. Patricia K. Kuhl (University of Washington, Seattle, USA)

PARIS--(BUSINESS WIRE)--Dec 2, 2011 - The international jury under the presidency of Prof. Albert Galaburda (Harvard Medical School, Boston, USA) awarded on November 29th, 2011 the 20th Jean-Louis Signoret Neuropsychology Prize of the Fondation Ipsen (Paris:IPN) (20.000€) to Prof. Prof. Patricia K. Kuhl (University of Washington, Seattle, USA) for her work that played a major role in the understanding of language acquisition and the neural bases of language.

Infants are born with innate abilities to easily identify every sound of every language, however, by the end of the first year of life, infants show a perceptual narrowing of their language skills. Their ability to discern differences in the sounds that make up words in the world’s languages shrinks. Nonnative sounds are no longer differentiated. This developmental transition is caused by two interacting factors: the child’s computational skills and their social brains. Computational skills allow rapid statistical learning and social interaction is necessary for this computational learning process to occur. Neuroimaging using Magnetoencephalography (MEG) may help explain the neuroplasticity of the child’s mind versus the more expert (but less open) mind of the adult, and account for the “critical period” for language. She also studied the early development of the brain of bilingual children. By 10 to 12 months bilingual infants do not show the perceptual narrowing of the monolingual children. This is another piece of evidence that experiences shape the brain.

Patricia Kuhl is a Professor of Speech and Hearing Sciences at the Institute for Brain and Learning Sciences at the University of Washington since 1977 and co-director of the Institute. Prof. Kuhl is a member of the National Academy of Science USA, the American Academy of Arts and Sciences and has been elected a fellow in the American Association for the Advancement of Science, the American Psychological Association, and the Association for Psychological Science. Prof. Kuhl was awarded the Silver Medal of the Acoustical Society of America in 1997, the Kenneth Craik Research Award from Cambridge University in 2005, and the Gold Medal from the acoustics branch of the American Institute of Physics in 2008.

About the Jean-Louis Signoret Neuropsychology Prize

Launched in 1992, this prize has been awarded by the Fondation Ipsen to many renowned specialists: Eric Kandel (1992), Jacques Paillard (1993), Rodolfo Llinas (1994), Stephen Kosslyn (1995), Alfonso Caramazza (1996), Jean-Pierre Changeux (1997), Edoardo Bisiach (1998), Joseph LeDoux (1999), Joaquin Fuster (2000), Stanislas Dehaene (2001), Deepak Pandya (2002), Uta Frith (2003), Hanna and Antonio Damasio (2004), Marc Jeannerod (2005), Faraneh Vargha-Khadem (2006), Alvaro Pascual Leone (2007), Elizabeth Warrington (2008), Pierre Maquet (2009) and Giacomo Rizzolati (2010).

The jury members are: Albert Galaburda (Harvard Medical School, Boston, USA), President, Jocelyne Bachevalier (Emory University, Atlanta, USA), Laurent Cohen (Hôpital de la Salpétrière, Paris, France), Branch Coslett (University of Pennsylvania, Philadelphia, USA), Richard Frackowiak (CHUV, Lausanne, Switzerland), Didier Hannequin (Hôpital Charles Nicolle, Rouen, France), Kenneth Heilman (University of Florida, Gainesville, USA), Bernard Laurent (Hôpital Bellevue, Saint-Etienne, France), Kimford Meador (Emory University, Atlanta, USA), Michel Poncet (C.H.U. Hôpital Timone, Marseille, France), Donald Stuss (The Rotman Research Institute, Toronto, Canada).

La Fondation Ipsen

Established in 1983 under the aegis of the Fondation de France, the mission of the Fondation Ipsen is to contribute to the development and dissemination of scientific knowledge. The long-standing action of the Fondation Ipsen aims at fostering the interaction between researchers and clinical practitioners, which is indispensable due to the extreme specialisation of these professions. The ambition of the Fondation Ipsen is to initiate a reflection about the major scientific issues of the forthcoming years. It has developed an important international network of scientific experts who meet regularly at meetings known as Colloques Médecine et Recherche, dedicated to six main themes: Alzheimer's disease, neurosciences, longevity, endocrinology, the vascular system and cancer science. Moreover, in 2007, the Fondation Ipsen started three new series of meetings. The first series is an annual meeting organized in partnership with the Salk Institute and Nature and focuses on Biological Complexity; the second series is the “Emergence and Convergence” series with Nature, and the third with Cell and the Massachusetts General Hospital entitled “Exciting Biologies”. Since its beginning, the Fondation Ipsen as organised more than 100 international conferences, published 72 volumes with renowned publishers and 219 issues of a widely distributed bimonthly newsletter Alzheimer Actualités. It has also awarded more than 100 prizes and grants.

Neuropsychology Abstract of the Day: Hippocampal Function and Alzheimer's Disease

Hippocampal hyperactivation associated with cortical thinning in Alzheimer's disease signature regions in non-demented elderly adults
Journal of Neuroscience. 2011 Nov 30; 31(48): 17680-17688
Putcha D, Brickhouse M, O'Keefe K, Sullivan C, Rentz D, Marshall G, Dickerson B, Sperling R


Alzheimer's disease (AD) is associated with functional and structural alterations in a distributed network of brain regions supporting memory and other cognitive domains. Functional abnormalities are present in mild cognitive impairment (MCI) with evidence of early hyperactivity in medial temporal lobe regions, followed by failure of hippocampal activation as dementia develops. Atrophy in a consistent set of cortical regions, the "cortical signature of AD," has been reported at the stage of dementia, MCI, and even in clinically normal (CN) older individuals predicted to develop AD. Despite multiple lines of evidence for each of these findings, the relationship between this structural marker of AD-related neurodegeneration and this functional marker of the integrity of the episodic memory system has not yet been elucidated. We investigated this relationship in 34 nondemented older humans (CN, N = 18; MCI, N = 16). Consistent with previous studies, we found evidence of hippocampal hyperactivation in MCI compared with CN. Additionally, within this MCI group, increased hippocampal activation correlated with cortical thinning in AD-signature regions. Even within the CN group, increased hippocampal activity was negatively correlated with cortical thinning in a subset of regions, including the superior parietal lobule (r = -0.66; p < 0.01). These findings, across a continuum of nondemented and mildly impaired older adults, support the hypothesis that paradoxically increased hippocampal activity may be an early indicator of AD-related neurodegeneration in a distributed network.

PMID: 22131428 [PubMed - in process]

Wednesday, November 30, 2011

Neuropsychology Abstract of the Day: Olfaction and Neurodegenerative Disease

Just noticeable difference in olfaction: A discriminative tool between healthy elderly and patients with cognitive disorders associated with dementia
Rhinology. 2011 15 1; 49(5): 513-518.
Chopard G, Galmiche J, Jacquot L, Brand G


Olfactory dysfunction appears to be one of the earliest signs of several age-related neurodegenerative disorders, including Alzheimer`s disease (AD) or Parkinson`s disease (PD). To rate performance and olfactory deficits in patients with cognitive disorders, various olfactory tasks have been used such as odor detection, discrimination, recognition memory, identification and naming but no study has been focused on just noticeable difference (JND), a sensitive tool of detection. The aim of this study was to investigate and compare variations in JNDs in healthy elderly and in patients with cognitive disorders associated with dementia. The results showed significantly higher olfactory JNDs in a population with cognitive disorders associated with dementia - i.e. a lower olfactory detection performance - compared to a control population paired in age, gender and education level. Additionally, the findings of the present study showed strong correlations between cognitive performances and JND scores in the control population contrary to the patient population. These findings are discussed in relation to the relevance of using olfactory JNDs in the diagnosis of dementias.

PMID: 22125780 [PubMed - as supplied by publisher]

Anthony Risser

WNYC: "Free Will and the Science of the Brain"

Today on WYNC's Leonard Lopate show, Dr. Michael Gazzaniga.

Listen and/or download here

Tuesday, November 29, 2011

Neuropsychology Abstract of the Day: Moyamoya

Intellectual ability and executive function in pediatric moyamoya vasculopathy
Developmental Medicine and Child Neurology. 2011 Nov 24;
Williams TS, Westmacott R, Dlamini N, Granite L, Dirks P, Askalan R, Macgregor D, Moharir M, Deveber G


Aim  Moyamoya vasculopathy is characterized by progressive stenosis of the major arteries of the Circle of Willis, resulting in compromised cerebral blood flow and increased risk of stroke. The objectives of the current study were to examine intellectual and executive functioning of children with moyamoya and to evaluate the impact of moyamoya type, stroke (clinical or silent), vasculopathy laterality, and disease duration on neurocognitive abilities. Method  Thirty pediatric participants (mean age 10y 10mo, SD 4y; 18 females, 12 males) completed age-appropriate Wechsler Intelligence Scales before any therapeutic revascularization procedures. Reports of executive function were obtained from parents and teachers using the Behavior Rating Index of Executive Function. Results  Children with moyamoya scored significantly lower than the test standardization samples on all indices of intelligence and ratings of executive functioning (p<0.001). Patients did not differ by type of moyamoya or history of stroke. Patients with bilateral disease and stroke scored significantly lower than those with unilateral disease on measures of overall intellectual function (p=0.035) and verbal comprehension (p=0.04). Deficits in metacognitive executive functions were also more pronounced in bilateral patients according to teacher ratings. Interpretation  Children with moyamoya are at risk for intellectual and executive problems, exacerbated by bilateral disease and clinical stroke history.

PMID: 22117564 [PubMed - as supplied by publisher]

Clinical Trials: Moscow Rules

An interesting posting on the Pharmalot blog today:

Russian Trial Rules Are A ‘Serious Blow’ To Pharma
By Ed Silverman
November 29th, 2011 // 9:56 am

Read the blog post

Monday, November 28, 2011

Controversy over US Military Traumatic Brain Injury Cognitive Assessment

Today, NPR's All Things Considered will be airing a report it prepared with ProPublica about problems with the US military's approach to testing the cognitive function of individuals.

Here is a link to a ProPublica article about the issue:

Testing Program Fails Soldiers

An audio link and a transcript of the report will likely be made available by NPR on the All Things Considered website after it airs.

The ProPublica report includes links to a number of documents about the issue, for those interested in looking deeper into the controversy.

ADDENDUM: The NPR story can be listened to and/or downloaded at this link: Listen here.

Alzheimer’s Disease and Dementia Leadership Council

Alzheimer’s Disease and Dementia Leadership Council Holds Inaugural Meeting
Council convenes at the New York Academy of Sciences to discuss strategies for tackling barriers to translation in dementia.
Posted 11/28/2011

"NEW YORK, November 23, 2011- The newly created Alzheimer's Disease and Dementia Leadership Council gathered for its inaugural meeting at the New York Academy of Sciences on Tuesday, November 15. The leadership council, consisting of key opinion leaders in industry, academia, and government, is charged with creating strategic objectives for the Academy's Translational Science Initiative, which aims to accelerate the transfer of basic scientific discoveries into new methods for diagnosis, treatment, and prevention of disease, initially focused on Alzheimer's disease and dementia."

Read the full NYAS press release

From the One Mind for Research organization: Read the press release

Sunday, November 27, 2011

Elan and University of Cambridge to Create Neurodegenerative Research Institute

Elan to create research centre with Cambridge University
Sun Nov 27, 2011 4:14am EST

"(Reuters) - Elan Corp Plc has signed an agreement with Britain's Cambridge University to create a research center focused on therapies for Alzheimer's and Parkinson's, the Dublin-headquartered biotech group said on Sunday."

Read the full article

Addendum (28 November 2011):

From Cambirdge Business Media:
28 November 2011 12:32
$10m neuroscience drug discovery centre for Cambridge
Lautaro Vargas
Read the full article

Friday, November 25, 2011

Mind Wandering, Creativity, and Brain Function

CBC Radio's "Spark" show's Nora Young discusses this topic on its 30 October 2011 show.

Dr. Kalina Christoff, an assistant professor in the Psychology department and the Brain Research Centre at the University of British Columbia, is interviewed.

Available as a podcast from the show's webpage.

Thursday, November 24, 2011

Mild Cognitive Impairment (MCI)

A new post at the New York Times blog, "The New Old Age":

November 23, 2011, 12:18 PM
It’s Mild Cognitive Impairment. Now What?

"How would you react to a diagnosis of mild cognitive impairment — memory problems that allow you to continue normal daily activities, but presage an increased likelihood of developing Alzheimer’s disease within a few years?"

Read the full post

FDA: Insomnia Drug Approval

From the FDA:

For Immediate Release: Nov. 23, 2011

FDA approves first insomnia drug for middle-of-the-night waking followed by difficulty returning to sleep


The U.S. Food and Drug Administration today approved Intermezzo (zolpidem tartrate sublingual tablets) for use as needed to treat insomnia characterized by middle-of-the-night waking followed by difficulty returning to sleep.

This is the first time the FDA has approved a drug for this condition. Intermezzo should only be used when a person has at least four hours of bedtime remaining. It should not be taken if alcohol has been consumed or with any other sleep aid.

Insomnia is a common condition in which a person has trouble falling or staying asleep. It can range from mild to severe, depending on how often it occurs and for how long. Insomnia can cause excessive daytime sleepiness and lack of energy. It also can make a person feel anxious, depressed, or irritable. People with insomnia may have trouble focusing on tasks, paying attention, learning, and remembering.

Zolpidem tartrate was first approved in the United States in 1992 as the drug Ambien. Intermezzo is a lower dose formulation of zolpidem. The recommended and maximum dose of Intermezzo is 1.75 milligrams for women and 3.5 mg for men, taken once per night. The recommended dose for women is lower because women clear zolpidem from the body at a lower rate than men.

“For people whose insomnia causes them to wake in middle of the night with difficulty returning to sleep, this new medication offers a safer choice than taking a higher dose of zolpidem upon waking,” said Robert Temple, M.D., deputy center director for clinical science in the FDA’s Center for Drug Evaluation and Research. “With this lower dose there is less risk of a person having too much drug in the body upon waking, which can cause dangerous drowsiness and impair driving.”

Intermezzo was studied in two clinical trials involving more than 370 patients. In the studies, patients taking the drug had a shorter time to fall back asleep after waking compared to people taking an inactive pill (placebo). The most commonly reported adverse reactions in the clinical trials were headache, nausea and fatigue.

Like other sleep medicines, Intermezzo may cause serious side effects, including getting out of bed while not fully awake and doing an activity that you do not know you are doing or do not remember having done. Reported activities while under the influence of sleep medicines include driving a car, making and eating food, having sex, talking on the phone, and sleep walking—without knowing at the time or remembering later. Chances of such activity increase if a person has consumed alcohol or taken other medicines that make them sleepy.

Intermezzo is a federally controlled substance because it can be abused or lead to dependence.

Intermezzo is made by Transcept Pharmaceuticals Inc. of Port Richmond, Calif.


Read the full press release

Monday, November 21, 2011

Science Weekly Podcast: Understanding the Brain

This week's Science Weekly podcast from The Guardian includes a report about the Society for Neuroscience (SfN) annual conference ("the brainiest science conference on the planet") and a report about dementia.

Listen to the podcast here

Saturday, November 19, 2011

Neuropsychology Abstract of the Day: Hippocampal Atrophy

Hippocampal Subregions are Differentially Affected in the Progression to Alzheimer's Disease
Anat Rec (Hoboken). 2011 Nov 18;
Greene SJ, Killiany RJ,


Atrophy within the hippocampus (HP) as measured by magnetic resonance imaging (MRI) is a promising biomarker for the progression to Alzheimer's disease (AD). Subregions of the HP along the longitudinal axis have been found to demonstrate unique function, as well as undergo differential changes in the progression to AD. Little is known of relationships between such HP subregions and other potential biomarkers, such as neuropsychological (NP), genetic, and cerebral spinal fluid (CSF) beta amyloid and tau measures. The purpose of this study was to subdivide the hippocampus to determine how the head, body, and tail were affected in normal control, mild cognitively impaired, and AD subjects, and investigate relationships with HP subregions and other potential biomarkers. MRI scans of 120 participants of the Alzheimer's Disease Neuroimaging Initiative were processed using FreeSurfer, and the HP was subdivided using 3D Slicer. Each subregion was compared among groups, and correlations were used to determine relationships with NP, genetic, and CSF measures. Results suggest that HP subregions are undergoing differential atrophy in AD, and demonstrate unique relationships with NP and CSF data. Discriminant function analyses revealed that these regions, when combined with NP and CSF measures, were able to classify by diagnostic group, and classify MCI subjects who would and would not progress to AD within 12 months. Anat Rec,, 2011. © 2011 Wiley Periodicals, Inc.

PMID: 22095921 [PubMed - as supplied by publisher]

Wellcome Trust Blog: "What I Learned at the BBC"

An interesting post on the Wellcome Trust Blog:

What I Learned at the BBC
By Johanna Hoog
18 November 2011

A look at how science gets on television.

Read the post

Friday, November 18, 2011

Neuropsychology Abstract of the Day: Alzheimer's Disease

Increasing the diagnostic accuracy of medial temporal lobe atrophy in Alzheimer's disease
Journal of Alzheimer's Disease. 2011;25(3):477-90
Jacobs HI, Van Boxtel MP, van der Elst W, Burgmans S, Smeets F, Gronenschild EH, Verhey FR, Uylings HB, Jolles J


Medial temporal lobe (MTL) atrophy is considered to be one of the most important predictors of Alzheimer's disease (AD). This study investigates whether atrophy in parietal and prefrontal areas increases the predictive value of MTL atrophy in three groups of different cognitive status. Seventy-five older adults were classified as cognitively stable (n = 38) or cognitively declining (n = 37) after three years follow-up. At follow-up, the grey matter of the MTL, inferior prefrontal cortex (IPC), and inferior parietal lobule (IPL) was delineated on MRI scans. Six years later, a dementia assessment resulted in distinguishing and separating a third group (n = 9) who can be considered as preclinical AD cases at scan time. Ordinal logistic regressions analysis showed that the left and right MTL, as well as the right IPC and IPL accurately predicted group membership. Receiver Operating Curves showed that the MTL was best in distinguishing cognitively stable from cognitively declining individuals. The accuracy of the differentiation between preclinical AD and cognitively stable participants improved when MTL and IPL volumes were combined, while differentiating preclinical AD and cognitively declined participants was accomplished most accurately by the combined volume of all three areas. We conclude that depending on the current cognitive status of an individual, adding IPL or IPC atrophy improved the accuracy of predicting conversion to AD by up to 22%. Diagnosis of preclinical AD may lead to more false positive outcomes if only the MTL atrophy is considered.

PMID: 21471642 [PubMed - indexed for MEDLINE]

Thursday, November 17, 2011

Neuropsychology Abstract of the Day: Cognition in Depression

A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder
Journal of Affective Disorders. 2011 Nov 14;
Lee RS, Hermens DF, Porter MA, Redoblado-Hodge MA


BACKGROUND: Recurrent-episode Major Depressive Disorder (MDD) is associated with a number of neuropsychological deficits. To date, less is known about whether these are present in the first-episode. The current aim was to systematically evaluate the literature on first-episode MDD to determine whether cognition may be a feasible target for early identification and intervention. METHODS: Electronic database searches were conducted to examine neuropsychological studies in adults (mean age greater than 18years old) with a first-episode of MDD. Effect sizes were pooled by cognitive domain. Using meta-regression techniques, demographic and clinical factors potentially influencing heterogeneity of neuropsychological outcome were also investigated. RESULTS: The 15 independent samples reviewed yielded data for 644 patients with a mean age of 39.36years (SD=10.21). Significant cognitive deficits were identified (small to medium effect sizes) for psychomotor speed, attention, visual learning and memory, and all aspects of executive functioning. Symptom remission, inpatient status, antidepressant use, age and educational attainment, each significantly contributed to heterogeneity in effect sizes in at least one cognitive domain. LIMITATIONS: Reviewed studies were limited by small sample sizes and often did not report important demographic and clinical characteristics of patients. CONCLUSIONS: The current meta-analysis was the first to systematically demonstrate reduced neuropsychological functioning in first-episode MDD. Psychomotor speed and memory functioning were associated with clinical state, whereas attention and executive functioning were more likely trait-markers. Demographic factors were also associated with heterogeneity across studies. Overall, cognitive deficits appear to be feasible early markers and targets for early intervention in MDD.PMID: 22088608

[PubMed - as supplied by publisher]

Carl Zimmer on the Blood-Brain Barrier

On the Discover Magazine website:

Maybe You Do Need a Hole in Your Head—to Let the Medicine In
Carl Zimmer
November 2011
Read the article

Tuesday, November 15, 2011

Upcoming Event: National Academy of Neuropsychology (16-19 Nov 2011, Florida)

Here is the conference homepage to the National Academy of Neuropsychology's (NAN) annual conference, taking place this week in Florida:

Conference Homepage

Monday, November 14, 2011

Epilepsy News

A press release from the NIH:

Ultrathin flexible brain implant offers unique look at seizures in NIH-funded research
13 November 2011


Researchers funded by the National Institutes of Health have developed a flexible brain implant that could one day be used to treat epileptic seizures. In animal studies, the researchers used the device — a type of electrode array that conforms to the brain's surface — to take an unprecedented look at the brain activity underlying seizures.

"Someday, these flexible arrays could be used to pinpoint where seizures start in the brain and perhaps to shut them down," said Brian Litt, M.D., the principal investigator and an associate professor of neurology at the University of Pennsylvania School of Medicine in Philadelphia. The findings appear in this month's Nature Neuroscience. The team will also discuss their findings at the 2011 Society for Neuroscience meeting, Nov. 12-16 in Washington, D.C.

"This group's work reflects a confluence of skills and advances in electrical engineering, materials science and neurosurgery," said Story Landis, Ph.D., director of NIH's National Institute of Neurological Disorders and Stroke (NINDS), which helped fund the work. "These flexible electrode arrays could significantly expand surgical options for patients with drug-resistant epilepsy."


Read the full press release

Podcast: The Guardian's Science Weekly: "The Inscrutable Brain"

This week's Science Weekly podcast from The Guardian includes a segment called The Inscrutable Brain.


"On this week's show Alok Jha meets science writer Bryan Appleyard to discuss his new book The Brain is Wider than the Sky: Why Simple Solutions Don't Work in a Complex World. It's "part memoir and part reportage" on what he sees as our tendency to oversimplify the complexity of the human experience – particularly in the field of neuroscience – and misunderstand the limits of science."


Listen to the podcast

Friday, November 11, 2011


From a New York Times blog:

Preventing Hospital Delirium
November 11, 2011, 4:09 PM

Read the full blog entry

TC-5214 Depression Phase III Results

From Fierce Biotech:

Key AZ/Targacept depression drug flunks first Phase III test
By John Carroll
November 8, 2011 — 6:49am ET


"The high-profile depression drug TC-5214 has failed the first in a string of Phase III studies, dealing AstraZeneca's struggling R&D operation another stinging setback and walloping Targacept with a meltdown in its share value this morning."


Read the full article

Neuropsychology Abstract of the Day: Neuropsychological Rehabilitation for Multiple Sclerosis

Neuropsychological rehabilitation for multiple sclerosis
Cochrane Database Syst Rev. 2011;11:CD009131
Rosti-Otajärvi EM, Hämäläinen PI


BACKGROUND: Cognitive deficits are a common manifestation in multiple sclerosis (MS) and have a wide effect on the patient's quality of life. Alleviation of the harmful effects caused by these deficits should be a major goal of MS research and practice.

OBJECTIVES: The aim of this review was to evaluate the effects of neuropsychological/cognitive rehabilitation in MS by conducting a systematic review.

SEARCH STRATEGY: A systematic literature search was carried out on reports drawn from Cochrane MS Group Specialised Register (To October 2010), Evidence-based medicine (EBM) reviews (To September 2010), MEDLINE (January 1950 to September 2010), EMBASE (1974 to September 2010), PsycINFO (January 1806 to September 2010), WEB OF SCIENCE (WOS) (January 1986 to September 2010), CINAHL (1982 to September 2010), and identified from the references in these reports.

SELECTION CRITERIA: Randomised Controlled Trials (RCTs) and quasi-randomised trials evaluating the effects of neuropsychological rehabilitation in MS compared to other interventions or no intervention at all and employing neuropsychological rehabilitation methods and outcome measures were included.

DATA COLLECTION AND ANALYSIS: Two review authors individually judged the relevance, risk of bias, and content of the included studies. Results were combined quantitatively with meta-analyses according to the intervention type: 1) Cognitive training and 2) Cognitive training combined with other neuropsychological rehabilitation methods. In addition, narrative presentation was used in reporting the results of those studies which were inappropriate to be included in the meta-analysis.

MAIN RESULTS: Fourteen studies (770 MS patients) fulfilled the inclusion criteria. On the basis of these studies, low level evidence was found that neuropsychological rehabilitation reduces cognitive symptoms in MS. Cognitive training was found to improve memory span (standardised mean difference 0.54 (95% confidence interval 0.2 to 0.88, P = 0.002)), working memory (standardised mean difference 0.33 (95% confidence interval 0.09 to 0.57, P = 0.006)), and immediate visual memory (standardised mean difference 0.32 (95% confidence interval 0.04 to 0.6, P = 0.02)). There was no evidence of an effect of cognitive training combined with other neuropsychological rehabilitation methods on cognitive or emotional functions. The overall quality as well as the comparability of the included studies were relatively low due to methodological limitations and heterogeneity of outcome measures. Although most of the pooled results in the meta-analyses yielded no significant findings, twelve of the fourteen studies showed some evidence of positive effects when the studies were individually analysed.

AUTHORS' CONCLUSIONS: The review indicates low level evidence for the positive effects of neuropsychological rehabilitation in MS. Interventions included in the review were heterogeneous. Consequently, clinical inferences can basically be drawn from single studies. Therefore, new trials may change the strength and direction of the evidence. To further strengthen the evidence, well-designed high quality studies are needed. In this systematic review, recommendations are given for improving the quality of future studies on the effects of neuropsychological rehabilitation in MS.

PMID: 22071863 [PubMed - in process]

Dr. Brenda Milner

A new interview with Dr. Milner:

The Daily talks to McGill researcher Brenda Milner
Canadian neuroscientist honoured with Greengard Prize for achievements of women in science
The McGill Daily
Published on November 10, 2011

Read the full interview

Thursday, November 10, 2011

Neuropsychology Abstract of the Day: A Curious Dual-Task Study

Decrease in gait variability while counting backward: a marker of "magnet effect"?
Journal of Neural Transmission. 2010 Oct; 117(10): 1171-1176
Beauchet O, Allali G, Poujol L, Barthelemy JC, Roche F, Annweiler C


Counting backward (CB) and walking are both rhythmic tasks. An improvement of CB performance has been reported while walking, and has been interpreted as a "magnet effect" which is the tendency of biological oscillators to attract each other. The objective of this study was to compare the coefficient of variation (CoV) of stride time (ST) and the number of enumerated figures while single- and dual-tasking between older adults who increased and decreased their CoV of ST while CB. The number of enumerated figures and the CoV of ST under single-task (i.e., CB while sitting or walking alone) and dual-task (i.e., CB while walking) were measured among 100 community-dwelling older subjects (mean, 69.8 ± 0.07 years). Subjects were separated into two groups according to the dual-task-related changes in CoV of ST (i.e., either above or below the mean value of CoV of ST under single-task). Seventeen participants decreased their CoV of ST while CB compared to usual walking (2.6 ± 1.6% vs. 2.0 ± 1.3%, P < 0.001), while 83 increased their CoV of ST (1.7 ± 0.6% vs 3.4 ± 2.3%, P < 0.001). The subjects who decreased their CoV of ST had a tendency to enumerate more figures while walking compared to sitting (20.9 ± 6.3 vs 19.4 ± 4.7, P = 0.046) unlike those who increased their CoV of ST (20.3 ± 5.0 vs 21.8 ± 6.0 while sitting, P = 0.001). We found that most of subjects had worse gait and CB performance while dual-tasking. Conversely, a limited number of subjects improved significantly their gait performance and simultaneously had a tendency to improve their CB performance while walking compared to sitting. This behavior was observed only among subjects with the highest gait variability and could be interpreted as an implicit strategy based on the "magnet effect".

PMID: 20809070 [PubMed - indexed for MEDLINE]

Wednesday, November 09, 2011

Neuropsychology Abstract of the Day: Assessment

The measurement of everyday cognition: Development and validation of a short form of the Everyday Cognition scales
Alzheimers Dement. 2011 Nov; 7(6): 593-601.
Tomaszewski Farias S, Mungas D, Harvey DJ, Simmons A, Reed BR, Decarli C


BACKGROUND: This study describes the development and validation of a shortened version of the Everyday Cognition (ECog) scales [Tomaszewski Farias et al. Neuropsychology 2008;22:531-44], an informant-rated questionnaire designed to detect cognitive and functional decline.

METHODS: External, convergent, and divergent validities and internal consistency were examined. Data were derived from informant ratings of 907 participants who were either cognitively normal, had mild cognitive impairment (MCI), or had dementia.

RESULTS: Twelve items were included in the shortened version (ECog-12). The ECog-12 strongly correlated with established functional measures and neuropsychological scores, only weakly with age and education, and demonstrated high internal consistency. The ECog-12 showed excellent discrimination between the dementia and normal groups (area under the receiver operator characteristic curve = 0.95, CI = 0.94-0.97), and showed promise in discriminating normal older adults from those with any cognitive impairment (i.e., MCI or dementia). Discrimination between the MCI and normal groups was poor.

CONCLUSIONS: The ECog-12 shows promise as a clinical tool for assisting clinicians in identifying individuals with dementia.

PMID: 22055976 [PubMed - in process]

Monday, November 07, 2011

Tractometry and The Psychology Dept at Cardiff University

A new word (for me, at least) for a new discipline of study in neuropsychology and neuroscience. Best wishes, Prof. Jones!

Investigating the brain’s white matter
Cardiff University News Centre
07 November 2011


"Pioneering brain research at Cardiff has received a major boost with the winning of the University’s first prestigious Investigator Award from the Wellcome Trust.

"Professor Derek Jones, Director of Cardiff University Brain Repair Imaging Centre (CUBRIC), has received the Award to develop the new discipline of Tractometry."


Read the full article

Saturday, November 05, 2011

Dear Reader

Dear Reader,

If you are reading this blog and find that there are pop-up ads or framed ads around the edges or in a different format than you see if you were to use the blog's direct URL, then you might be viewing the blog through some cookie-directed third-party vendor (especially if you first accessed this blog via a third party not of the scope of a Google or a Twitter or a Yahoo. etc.).

If this happens to you at this blog (or, indeed, at other websites that you visit), you might want to try cleaning your collection of cookies and re-entering the site directly from the BrainBlog URL.

Hopefully, this hasn't happened. However, I have heard from some other bloggers that their readers have had recent problems of this type.

Best wishes,


The Cerebellum and Neuropsychological Function

This sounds like a good read:

O'Halloran CJ, Kinsella GJ, & Storey E. (2011). The cerebellum and neuropsychological functioning: A critical review Journal of Clinical and Experimental Neuropsychology..

Friday, November 04, 2011

Upcoming Event: SfN's Neuroscience 2011 (12-16 Nov, Washington, DC)

Here is the website, chock full of information, for the Society for Neuroscience's annual meeting, Neuroscience 2011:

Neuroscience 2011

Computerized Cognitive Testing: A New CogState Paper

Reliability of repeated cognitive assessment of dementia using a brief computerized battery
American Journal of Alzheimers Disease and Other Dementias. 2011 Jun; 26(4): 326-333.
Hammers D, Spurgeon E, Ryan K, Persad C, Heidebrink J, Barbas N, Albin R, Frey K, Darby D, Giordani B


OBJECTIVE: The aim of this study was to evaluate the short-term stability and reliability of a brief computerized cognitive battery in established dementia types.
METHOD: Patients were administered the computerized battery twice with administrations approximately 2 hours apart, with intervening conventional neuropsychological tests. Patients were classified clinically, via consensus conference, as healthy controls (n = 23), mild cognitive impairment (n = 20), Alzheimer's disease (n = 52), dementia with Lewy Bodies ([DLB], n = 10), or frontotemporal dementia (n = 9).
RESULTS: Minimal practice effects were evident across Cog-State test administrations. Small magnitude improvements were seen across all groups on a working memory task, and healthy controls showed a mild practice effect on the accuracy of associative learning.
CONCLUSIONS: In established dementia, administration of the CogState tasks appears sensitive to cognitive impairment in dementia. Repeat administration also provided acceptable stability and test-retest reliability with minimal practice effects at short test-retest intervals despite intervening cognitive challenges.

PMID: 21636581 [PubMed - indexed for MEDLINE]

The Purpose of the Brain

A TEDtalk by University of Cambridge neuroscientist Daniel Wolpert:


From the webpage:

"Neuroscientist Daniel Wolpert starts from a surprising premise: the brain evolved, not to think or feel, but to control movement. In this entertaining, data-rich talk he gives us a glimpse into how the brain creates the grace and agility of human motion."

More on Dr. Brenda Milner's Newest Award

Pearl Meister Greengard Prize website

From the Montreal Gazette:

Montreal scientist wins Pearl Meister Greengard Prize
Montreal Gazette
November 3, 2011

"Neuropsychologist Dr. Brenda Milner was presented the Pearl Meister Greengard Prize at an award ceremony at Rockefeller University in New York on Thursday."

Read the full article

Thursday, November 03, 2011

Neuropsychology Abstract of the Day: Alzheimer's Disease

Relationships Between Behavioral Syndromes and Cognitive Domains in Alzheimer Disease: The Impact of Mood and Psychosis
American Journal of Geriatric Psychiatry. 2011 Nov 1;
Koppel J, Goldberg TE, Gordon ML, Huey E, Davies P, Keehlisen L, Huet S, Christen E, Greenwald BS


OBJECTIVES:: Behavioral disturbances occur in nearly all Alzheimer disease (AD) patients together with an array of cognitive impairments. Prior investigations have failed to demonstrate specific associations between them, suggesting an independent, rather than shared, pathophysiology. The objective of this study was to reexamine this issue using an extensive cognitive battery together with a sensitive neurobehavioral and functional rating scale to correlate behavioral syndromes and cognitive domains across the spectrum of impairment in dementia. DESIGN:: Cross-sectional study of comprehensive cognitive and behavioral ratings in subjects with AD and mild cognitive impairment. SETTING:: Memory disorders research center. PARTICIPANTS:: Fifty subjects with AD and 26 subjects with mild cognitive impairment; and their caregivers. MEASUREMENTS:: Cognitive rating scales administered included the Mini-Mental State Examination; the Modified Mini-Mental State Examination; the Boston Naming Test; the Benton Visual Retention Test; the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychology Assessment; the Controlled Oral Word Test; the Wechsler Memory Scale logical memory I and logical memory II task; the Wechsler Memory Scale-Revised digit span; the Wechsler Adult Intelligence Scale-Revised digit symbol task; and the Clock Drawing Task together with the Clinical Dementia Rating Scale and the Neuropsychiatric Inventory. RESULTS:: Stepwise regression of cognitive domains with symptom domains revealed significant associations of mood with impaired executive function/speed of processing (Δr = 0.22); impaired working memory (Δr = 0.05); impaired visual memory (Δr = 0.07); and worsened Clinical Dementia Rating Scale (Δr = 0.08). Psychosis was significantly associated with impaired working memory (Δr = 0.13). CONCLUSIONS:: Mood symptoms appear to impact diverse cognitive realms and to compromise functional performance.

PMID: 22048323 [PubMed - as supplied by publisher]


The BBC Newspod podcast of the 1st of November discusses schizophrenia a hundred years on.

It occurs in the final four minutes of the podcast, available from the BBC website and from iTunes as a free download.

Tuesday, November 01, 2011

Science Communication Conference 2012

Science Communication Conference 2012
Wellcome Trust Blog
31 October 2011
by Mun-Keat Looi


"The British Science Association, in partnership with the Wellcome Trust, have opened a call for proposals to run sessions at the 2012 Science Communication Conference.

"The conference will again be held at Kings Place, London, on Mon 14 & Tues 15 May 2012 and address key issues facing science communicators. It’s always a good opportunity to network, share ideas and good practice."


Read the full blog entry

Cognitive Enhancing Drugs

From The University of Cambridge:

The Ethics of Smart Drugs
31 October 2011
Read the full article here

Upcoming Videocast: The Neuroimaging of Pain (07 Nov 2011)

From a press release from the NIH:

Stanford researcher to speak at NIH on the role of neuroimaging in understanding pain

NCCAM presents Opening Windows to the Brain: Lessons Learned in the Neuroimaging of Pain


Sean Mackey, M.D., Ph.D., chief of the Pain Management Division and associate professor of anesthesia and pain management at the Stanford University School of Medicine, Stanford, Calif., will be the featured speaker for the third annual Stephen E. Straus Distinguished Lecture in the Science of Complementary and Alternative Medicine. Dr. Mackey’s lecture is entitled Opening Windows to the Brain: Lessons Learned in the Neuroimaging of Pain.

Millions of Americans suffer from pain that is chronic, severe, and not easily managed. People who suffer from chronic pain may take various prescription and non-prescription medications; these do not always provide adequate relief and may have unwanted side effects. As a result, people sometimes turn to non-pharmacological strategies for pain management. Dr. Mackey will discuss the role of neuroimaging and how it provides a picture for the principal mechanisms involved in pain processing, perception, and plasticity. He will also discuss the role of neural (brain) reward systems in regulating pain, and the potential future for non-pharmacological strategies to reduce the experience of pain.

Monday, Nov. 7, 2011, 9 a.m. to 10 a.m. EST

National Institutes of Health, Building 10, 10 Center Drive, Bethesda, Md. Lecture: Lipsett Amphitheater. It will also be videocast at when the event is live.


Read the full release

Monday, October 31, 2011

Neuropsychology Abstract of the Day: Alzheimer's Disease Pharmacologic Strategies

New pharmacological strategies for treatment of Alzheimer's disease: focus on disease-modifying drugs
British Journal of Clinical Pharmacology. 2011 Oct 28;
Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F


Current approved drug treatments for Alzheimer disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine. These drugs provide symptomatic relief but poorly affect the progression of the disease. Drug discovery has been directed, in the last ten years, to develop "disease-modifying drugs" hopefully able to counteract the progression of AD. Because in a chronic, slow progressing pathological process, such as AD, an early start of treatment enhances the chance of success, it is crucial to have biomarkers for early detection of AD-related brain dysfunction, usable before clinical onset. Reliable early biomarkers need therefore to be prospectively tested for predictive accuracy, with specific cutoff values validated in clinical practice. Disease-modifying drugs developed so far include drugs to reduce β amyloid (Aβ) production, drugs to prevent Aβ aggregation, drugs to promote Aβ clearance, drugs targeting tau phosphorylation and assembly, and other approaches. Unfortunately none of these drugs has demonstrated efficacy in phase 3 studies. The failure of clinical trials with disease-modifying drugs rises a number of questions, spanning from methodological flaws to fundamental understanding of AD patho-physiology and biology. Recently, new diagnostic criteria applicable to presymptomatic stages of AD have been published. These new criteria may impact drug development, such that future trials on disease-modifying drugs will include populations susceptible to AD, before clinical onset. Specific problems with completed trials and hopes with ongoing trials are discussed in this review.

PMID: 22035455 [PubMed - as supplied by publisher]

Sunday, October 30, 2011

Neuropsychology Abstract of the Day: MCI

Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: A meta-analysis
Journal of Neurology Neurosurgery and Psychiatry. 2011 Oct; 82(10): 1149-1156.
Elias-Sonnenschein LS, Viechtbauer W, Ramakers IH, Verhey FR, Visser PJ


BACKGROUND: The identification of subjects with mild cognitive impairment (MCI) at high risk for Alzheimer's disease (AD) is important for prognosis and early intervention. The APOE-ε4 allele is the strongest known genetic risk factor for AD. The authors performed a meta-analysis to establish the predictive accuracy of the APOE-ε4 allele for progression from MCI to AD-type dementia.

METHODS: The authors included 35 prospective cohort studies of subjects with MCI, including 6095 subjects, of whom 1236 progressed to AD-type dementia after 2.9 years of follow-up. Pooled estimates of the OR, sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) were obtained using random-effects models.

RESULTS: The OR for subjects with MCI who are carriers of APOE-ε4 allele to progress to AD-type dementia was 2.29 (95% CI 1.88 to 2.80), the sensitivity was 0.53 (95% CI 0.46 to 0.61), the specificity was 0.67 (95% CI 0.62 to 0.71), the PPV was 0.57 (95% CI 0.48 to 0.66), the NPV was 0.75 (95% CI 0.70 to 0.80), the LR+ was 1.60 (95% CI 1.48 to 1.72), and the LR- was 0.75 (95% CI 0.67 to 0.82). Meta-regression showed that sensitivity, specificity and NPV were dependent on age, APOE-ε4 allele background prevalence or follow-up length.

CONCLUSIONS: The APOE-ε4 allele is associated with a moderately increased risk for progression from MCI to AD-type dementia. The low sensitivity and PPV makes genotyping of limited value for predicting AD-type dementia in clinical practice. For trials aiming to prevent progression from MCI to AD-type dementia, APOE genotyping may be useful in selecting subjects with a higher risk for progression to AD-type dementia.

PMID: 21493755 [PubMed - indexed for MEDLINE]

Saturday, October 29, 2011

Neuropsychology Abstract of the Day: Amyloid

Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation
Neuron. 2011 Sep 8; 71(5): 833-844.
Kummer MP, Hermes M, Delekarte A, Hammerschmidt T, Kumar S, Terwel D, Walter J, Pape HC, König S, Roeber S, Jessen F, Klockgether T, Korte M, Heneka MT


Part of the inflammatory response in Alzheimer's disease (AD) is the upregulation of the inducible nitric oxide synthase (NOS2) resulting in increased NO production. NO contributes to cell signaling by inducing posttranslational protein modifications. Under pathological conditions there is a shift from the signal transducing actions to the formation of protein tyrosine nitration by secondary products like peroxynitrite and nitrogen dioxide. We identified amyloid β (Aβ) as an NO target, which is nitrated at tyrosine 10 (3NTyr(10)-Aβ). Nitration of Aβ accelerated its aggregation and was detected in the core of Aβ plaques of APP/PS1 mice and AD brains. NOS2 deficiency or oral treatment with the NOS2 inhibitor L-NIL strongly decreased 3NTyr(10)-Aβ, overall Aβ deposition and cognitive dysfunction in APP/PS1 mice. Further, injection of 3NTyr(10)-Aβ into the brain of young APP/PS1 mice induced β-amyloidosis. This suggests a disease modifying role for NOS2 in AD and therefore represents a potential therapeutic target.

PMID: 21903077 [PubMed - indexed for MEDLINE]

Friday, October 28, 2011

Neuropsychology Abstract of the Day: Mild Cognitive Impairment

There have been a number of excellent papers published over the past month in a number of different journals on the topic of Mild Cognitive Impairment (MCI). Looking forward to reading this new paper:

An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the national Alzheimer's coordinating center
American Journal of Geriatric Psychiatry. 2011 Nov; 19(11): 940-950.
Hanfelt JJ, Wuu J, Sollinger AB, Greenaway MC, Lah JJ, Levey AI, Goldstein FC


OBJECTIVES: : To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups.

DESIGN: : Latent class analysis using 1,655 patients with MCI.

SETTING: : Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health-supported Alzheimer's Disease Centers.

PARTICIPANTS: : Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination score of 22 or greater.

MEASUREMENTS: : UDS cognitive battery, Neuropsychiatric Inventory Questionnaire, and Functional Assessment Questionnaire administered at initial visit.

RESULTS: : Seven empirically based subgroups of MCI were identified: 1) minimally impaired (relative frequency, 12%); 2) amnestic only (16%); 3) amnestic with functional and neuropsychiatric features (16%); 4) amnestic multidomain (12%); 5) amnestic multidomain with functional and neuropsychiatric features (12%); 6) functional and neuropsychiatric features (15%); and 7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score of 4 or greater, an indicator of probable CVD.

CONCLUSIONS: : Findings suggest that there are several distinct phenotypes of MCI characterized by prominent cognitive features, prominent functional features, and neuropsychiatric features or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests that there may be distinct differences in disease etiology from the other phenotypes.

PMID: 22024618 [PubMed - in process]

Thursday, October 27, 2011

Neuropsychology Abstract of the Day: Pediatric Epilepsy and Memory Assessment

Everyday verbal memory and pediatric epilepsy
Epilepsy and Behavior. 2011 Jul; 21(3): 285-290.
Chapieski L, Evankovich K, Hiscock M, Collins R


This study addressed the reliability and validity of reports of everyday verbal memory with a sample of 132 pediatric patients with epilepsy. Each patient and one parent completed a questionnaire on everyday verbal memory comprising two scales assessing learning/retrieval and prospective memory. Each patient was also administered tests of memory, attention, and academic skills. Information about attention, mood, and academic performance was obtained from parent and teacher report, as well as self-report. Memory test scores were correlated with children's reports of learning and retrieval in everyday activities, but were not significantly associated with reports of prospective memory. Reports of everyday memory were found to be reliable and predictive of academic performance. Performance on tests of memory, conversely, was unrelated to reports of academic performance. Reports of everyday memory may, therefore, provide more useful information than tests when evaluating the effects of epilepsy and its treatments.

PMID: 21620770 [PubMed - indexed for MEDLINE]

Temporal Integration

A paper about temporal integration and the psychological present, available as a free download:

Wittmann, M. (2011). Moments in time. Frontiers in Integrative Neuroscience.
published: 18 October 2011
doi: 10.3389/fnint.2011.00066

Free download pdf

Wednesday, October 26, 2011

Book Review: "Kraken" by Wendy Williams

This post, and all others on BrainBlog, are written by Anthony Risser for his blog BrainBlog. The appearance of this entry, and others, on different websites, framed under different websites, or not at the BrainBlog URL do not have my permission. All rights retained.

Wendy Williams
Kraken: The curious, exciting, and slightly disturbing science of squid
NY: Abrams Image (2011)
ISBN 978-0-8109-8465-3

My guess is that, unlike biology students, many psychology students exposed to their first courses in biopsychology and neuroscience have little idea about cephalopods and their role played in our knowledge about the nervous system and behavior. (Hint: You are likely to have found squid in your textbook, in that diagram which shows the recording of electrical activity from a generic single neuron and its axon.)

Wendy Williams’ new book, Kraken, is a curious book that gives credit to the cephalopods and to the scientists who respect them and learn from them. It is a brief book with a nicely moving narrative. It is accessible to a general audience. It introduces the reader to a community of scientists (professional and amateur) who search for and study squid, cuttlefish, and octopus. People like Julie Taylor and Bill Gilly who work with the Humboldt squid. People like Bruce Andersen who teach neurosurgeons how to remove the single giant axon of Loligo pealei in a manner that will allow it to function for several hours after its removal. The book’s photographs are notably lo-tech; it is easy to imagine the subjects of the pictures posing for (or trying to avoid) the author’s pocket cam.

Collections of Loligo pealei offered up their giant axons to allow Alan Hodgkin and Andrew Huxley to appreciate the action potential and the movement of ions across the cell membrane. Nobel-award winning work that, though the author believes that cephalopods themselves deserve a Nobel for their overall contributions to medicine and science (not entirely tongue-in-cheek!).

Neuroscience is an important part of the story, but it certainly not the only part. Cephalopods have survived several mass extinctions on Earth and their story takes on many different elements. Simply advancing knowledge from mythology was an important part of cephalopod investigations in the 19th and early 20th centuries. The so-called ‘Monsters of the Deep’ are still part of B-movie plots, but we thrill more in the 21st century to their bioluminescence (which has been translated into a methodology to study functioning neurons), their response to their environment, their problem-solving abilities, and rises and falls in their numbers. Returning to the nervous system and behavior, the final pages of the book are a fascinating look at the intelligence of cephalopods or, more clearly, how could one determine the "intelligence" of animals other than humans. There are volumes and volumes available about this issue, but the coverage here is succinct and creative.

In all, a charming book.

Ahoy! A lagniappe for the curious: Many of the topics portrayed in the book (and other things about cephalopods) are available by others who have posted videos on YouTube. Like any salty 19th century seafarer, just search for cephalopods.

UC San Francisco-Pfizer Drug Development Partnership

From EurekaAlert:

UCSF-Pfizer partnership yields projects aimed at clinical trials
26 October 2011

Read the full article

An Award for Dr. Brenda Milner

From the Scientific American blog:

The 2011 Pearl Meister Greengard Prize: Honoring Dr. Brenda Milner for her pioneering work in cognitive neuroscience
By Jeanne Garbarino
October 26, 2011 |

Read the blog post about the award

Amyloid Precursor Protein Processing and Alzheimer’s Disease

An NIH Public Access Author Manuscript:

Richard J. O’Brien and Philip C. Wong
Amyloid Precursor Protein Processing and Alzheimer’s Disease
Published in final edited form as:
Annu Rev Neurosci. 2011 ; 34: 185–204. doi:10.1146/annurev-neuro-061010-113613.

Download the free-access pdf here

This looks like a fine overview of our current knowledge.

Neuropsychology Abstract of the Day: Visual Memory Assessment

Landscape test for assessing visual memory in Alzheimer's disease
Rev Neurol. 2011 Jul 1; 53(1): 1-7
Valls-Pedret C, Olives J, Bosch B, Caprile C, Castellví M, Molinuevo JL, Rami L


INTRODUCTION: Visual episodic memory is affected in the early phases of Alzheimer's disease (AD).

AIMS: To design a visual memory test free of any verbal content, to offer its normative values in the elderly population in Spain, to validate the test in a group of patients with mild AD and to determine its capacity to discriminate between subjects with AD and controls.

SUBJECTS AND METHODS: The study involved a sample of 263 subjects (137 controls and 126 patients with AD) over 50 years of age. The landscape test consists of a first part in which participants are shown 25 photographs of landscapes. Five minutes later, the previous 25 photos are shown again together with 25 new pictures, and the subject must recognise the ones that have already been seen. The statistical analysis was performed using the Student t test for independent measures, ANCOVA, linear regression, Pearson's correlation and the ROC curve.

RESULTS: In the control group, sex and schooling did not have any significant effect on the results, although differences were found between the youngest group (50-59 years) and the oldest age group (equal to or above 80 years). Findings show that there is a significant difference between the mean scores on the landscape test obtained by the two groups (control: 44.06 ± 3.2; AD: 34.25 ± 6.6; p < 0.001). The area under the curve from the landscape test was 0.904, with a sensitivity of 0.82 and a specificity of 0.85.

CONCLUSIONS: The landscapes test is a simple, sensitive and novel instrument for assessing visual memory in early AD.

PMID: 21678318 [PubMed - indexed for MEDLINE]

From the Wellcome Trust Blog

A good read from today, an entry at the Wellcome Trust blog:

Craters, blisters and Pringles: Do small irregularities on the brain surface give us clues about its functions?
26 October 2011
Read the blog post

This Week's All in the Mind from BBC Radio 4

This week's All in the Mind podcast from BBC Radio 4:

Visit the show's webpage to listen or to download the episode

From the webpage:

"How can a good night's sleep improve your memory? Why does the answer to a crossword clue suddenly appear first thing in the morning after a night's rest? In this week's programme Claudia Hammond talks to psychologist, Kimberly Fenn about what happens in the brain when we sleep and why it can significantly improve our memory. Hysteria or conversion disorder is surprisingly, not confined to medical history. Nearly 1 in 5 patients seen by neurologists will have symptoms like paralysis, fits or loss of vision which can't be explained neurologically. Claudia talks to neurologist, Mark Edwards and psychiatrist, Richard Kanaan about the history of conversion disorder, how common it is today, the best way to treat it and its complex causes. Also in the programme, Claudia meets the carers getting involved in mental health research and why their input is making a a difference to research projects exploring mental health across the country."

(Running length = 30 mins.)

Tuesday, October 25, 2011

Parliamentary Private Members' Debate on Medication Use in ADHD

A discussion about ADHD and medication was held today as a Private Members' Debate at Westminster. Set by Pat McFadden MP (pictured above), the debate includes response by the Minister of State, Department of Health.

Available for streaming at Parliament TV Go to the 25th of October, Westminster Hall at advance to 1330 hrs.

Background resource: The 2008 NICE guideline about ADHD.

Neuropsychology Abstract of the Day: Cortical Neuroanatomy of Neuropsychological Deficits

The cortical neuroanatomy of neuropsychological deficits in mild cognitive impairment and Alzheimer's disease: A surface-based morphometric analysis
Neuropsychologia. 2011 Oct 15;
Ahn HJ, Seo SW, Chin J, Suh MK, Lee BH, Kim ST, Im K, Lee JM, Lee JH, Heilman KM, Na DL


Patients with probable Alzheimer's disease (AD) and the amnesic form of mild cognitive impairment (aMCI) often demonstrate several types of neuropsychological deficits. These deficits are often related to cortical atrophy, induced by neuronal degradation. The purpose of this study is to investigate whether different anatomic patterns of cortical atrophy are associated with specific neuropsychological deficits. The participants were 170 patients with AD and 99 patients with aMCI. All participants underwent the Seoul Neuropsychological Screening Battery (SNSB), which includes tests that assess attention, language, visuospatial functions, verbal and visual memory, and frontal/executive functions. Cortical atrophy (thinning) was quantified by measuring the thickness of the cortical mantle across the entire brain using automated, three-dimensional magnetic resonance imaging. The relationship between cortical thickness and neuropsychological performance was analysed using stepwise multiple linear regression analyses. These analyses (corrected P<.001) showed that several specific brain regions with cortical thinning were associated with cognitive dysfunction including: digit span backward, verbal and picture recall, naming and fluency, drawing-copying, response inhibition and selective attention. Some of the other functions, however, were not associated with specific foci of cortical atrophy (digit span forward, the word reading portion of the Stroop test, word and picture recognition). Our study, involving a large sample of participants with aMCI and AD, provides support for the postulate that cortical thinning-atrophy in specific anatomic loci are pathological markers for specific forms of cognitive dysfunction.

PMID: 22019776 [PubMed - as supplied by publisher]

Monday, October 24, 2011

'What is Alzheimer's Disease" by thevisualmd

This new video about Alzheimer's disease is getting some coverage in the media today:

It comes from

View the video

Upcoming Event: Alzheimer's Seminar (White Plains, NY; 04 Nov 2011)

The Alzheimer’s Association Annual Research Seminar
Burke Rehabilitation Hospital
White Plains, NY

04 November 2011

Read news article


"The annual seminar focuses on the latest research as well as treatment options for the disease. Barry Jordan, M.D., Director of the ADAC and Director of the Memory Evaluation and Treatment Service (METS) at Burke, will speak on “Differential Diagnosis of Dementia.” According to Dr. Jordan, “This type of program is an important forum for researchers, families and the public to share information about the latest in Alzheimer’s research,” he said. “Burke is proud to have hosted this event for the past several years,” he added."


Alzheimer Disease Treatment

The current (October 2011) issue of the Canadian Journal of Psychiatry has free-download access to two review articles dealing with Alzheimer's disease. One deals with drug treatment, whilst the other addresses non-pharmacolgic treatments. An editiorial by Serge Gauthier (also a free download) introduces the issue.

Canadian Journal of Psychiatry

News from the FDA: Onfi tablets (clobazam) for Adjunctive Treatment in Lennox-Gastaut Syndrome

From the FDA:

For Immediate Release: Oct. 24, 2011

FDA approves Onfi to treat severe type of seizures

On Oct. 21, the U.S. Food and Drug Administration approved Onfi tablets (clobazam) for use as an adjunctive (add-on) treatment for seizures associated with Lennox-Gastaut syndrome in adults and children 2 years of age and older. As Onfi is intended to treat a disease or condition that affects fewer than 200,000 people in the United States, it was granted orphan drug designation by the FDA.

“Lennox-Gastaut syndrome is a severe form of epilepsy that causes debilitating seizures,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This is a difficult condition to treat, and it will be helpful to have an additional treatment option.”

Read the full release

Neuropsychology Abstract of the Day: A Leisurely Curiousity

Training-induced neural plasticity in golf novices
Journal of Neuroscience. 2011 Aug 31; 31(35): 12444-8.
Authors: Bezzola L, Mérillat S, Gaser C, Jäncke L


Previous neuroimaging studies in the field of motor learning have shown that learning a new skill induces specific changes of neural gray and white matter in human brain areas necessary to control the practiced task. Former longitudinal studies investigating motor skill learning have used strict training protocols with little ecological validity rather than physical leisure activities, although there are several retrospective and cross-sectional studies suggesting neuroprotective effects of physical leisure activities. In the present longitudinal MRI study, we used voxel-based morphometry to investigate training-induced gray matter changes in golf novices between the age of 40 and 60 years, an age period when an active life style is assumed to counteract cognitive decline. As a main result, we demonstrate that 40 h of golf practice, performed as a leisure activity with highly individual training protocols, are associated with gray matter increases in a task-relevant cortical network encompassing sensorimotor regions and areas belonging to the dorsal stream. A new and striking result is the relationship between training intensity (time needed to complete the 40 training hours) and structural changes observed in the parieto-occipital junction. Thus, we demonstrate that a physical leisure activity induces training-dependent changes in gray matter and assume that a strict and controlled training protocol is not mandatory for training-induced adaptations of gray matter.

PMID: 21880905 [PubMed - indexed for MEDLINE]

Sunday, October 23, 2011

Neuropsychology Abstract of the Day: Art and Neuroscience

Returning to a fav topic of mine, here is a new research study:

The right hemisphere in esthetic perception
Front Hum Neurosci. 2011;5:109
Bromberger B, Sternschein R, Widick P, Smith W, Chatterjee A


Little about the neuropsychology of art perception and evaluation is known. Most neuropsychological approaches to art have focused on art production and have been anecdotal and qualitative. The field is in desperate need of quantitative methods if it is to advance. Here, we combine a quantitative approach to the assessment of art with modern voxel-lesion-symptom-mapping methods to determine brain-behavior relationships in art perception. We hypothesized that perception of different attributes of art are likely to be disrupted by damage to different regions of the brain. Twenty participants with right hemisphere damage were given the Assessment of Art Attributes, which is designed to quantify judgments of descriptive attributes of visual art. Each participant rated 24 paintings on 6 conceptual attributes (depictive accuracy, abstractness, emotion, symbolism, realism, and animacy) and 6 perceptual attributes (depth, color temperature, color saturation, balance, stroke, and simplicity) and their interest in and preference for these paintings. Deviation scores were obtained for each brain-damaged participant for each attribute based on correlations with group average ratings from 30 age-matched healthy participants. Right hemisphere damage affected participants' judgments of abstractness, accuracy, and stroke quality. Damage to areas within different parts of the frontal parietal and lateral temporal cortices produced deviation in judgments in four of six conceptual attributes (abstractness, symbolism, realism, and animacy). Of the formal attributes, only depth was affected by inferior prefrontal damage. No areas of brain damage were associated with deviations in interestingness or preference judgments. The perception of conceptual and formal attributes in artwork may in part dissociate from each other and from evaluative judgments. More generally, this approach demonstrates the feasibility of quantitative approaches to the neuropsychology of art.

PMID: 22016728 [PubMed - in process]

Saturday, October 22, 2011

Celebrities with CNS Diseases: Glen Campbell

American cowboy singer, Glen Campbell, is touring the UK in a farewell tour. He has been diagnosed with Alzheimer's disease.

Here is a commentary from The Independent from the 21st of October:

"Letter from Simon Kelner: A poignant farewell to the Wichita Lineman"

UPDATE: A review of his performance, from The Telegraph: Read the article here.

Neuropsychology Abstract of the Day: Visuocognition

The Cambridge Car Memory Test: A task matched in format to the Cambridge Face Memory Test, with norms, reliability, sex differences, dissociations from face memory, and expertise effects
Behav Res Methods. 2011 Oct 20;
Dennett HW, McKone E, Tavashmi R, Hall A, Pidcock M, Edwards M, Duchaine B


Many research questions require a within-class object recognition task matched for general cognitive requirements with a face recognition task. If the object task also has high internal reliability, it can improve accuracy and power in group analyses (e.g., mean inversion effects for faces vs. objects), individual-difference studies (e.g., correlations between certain perceptual abilities and face/object recognition), and case studies in neuropsychology (e.g., whether a prosopagnosic shows a face-specific or object-general deficit). Here, we present such a task. Our Cambridge Car Memory Test (CCMT) was matched in format to the established Cambridge Face Memory Test, requiring recognition of exemplars across view and lighting change. We tested 153 young adults (93 female). Results showed high reliability (Cronbach's alpha = .84) and a range of scores suitable both for normal-range individual-difference studies and, potentially, for diagnosis of impairment. The mean for males was much higher than the mean for females. We demonstrate independence between face memory and car memory (dissociation based on sex, plus a modest correlation between the two), including where participants have high relative expertise with cars. We also show that expertise with real car makes and models of the era used in the test significantly predicts CCMT performance. Surprisingly, however, regression analyses imply that there is an effect of sex per se on the CCMT that is not attributable to a stereotypical male advantage in car expertise.

PMID: 22012343 [PubMed - as supplied by publisher]

Friday, October 21, 2011

WBUR Boston: Fade to Darkness: The Age of Alzheimer's

WBUR Boston has, this week, run a series of presentations about Alzheimer's disease. Here is the WBUR webpage that described their programming: WBUR Boston "Fade to Darkness" webpage

Neuropsychology Abstract of the Day: Methodology

Estimating Decision-Relevant Comparative Effects Using Instrumental Variables
Stat Biosci. 2011 Sep;3(1):6-27
Basu A


Instrumental variables methods (IV) are widely used in the health economics literature to adjust for hidden selection biases in observational studies when estimating treatment effects. Less attention has been paid in the applied literature to the proper use of IVs if treatment effects are heterogeneous across subjects. Such a heterogeneity in effects becomes an issue for IV estimators when individuals' self-selected choices of treatments are correlated with expected idiosyncratic gains or losses from treatments. We present an overview of the challenges that arise with IV estimators in the presence of effect heterogeneity and self-selection and compare conventional IV analysis with alternative approaches that use IVs to directly address these challenges. Using a Medicare sample of clinically localized breast cancer patients, we study the impact of breast-conserving surgery and radiation with mastectomy on 3-year survival rates. Our results reveal the traditional IV results may have masked important heterogeneity in treatment effects. In the context of these results, we discuss the advantages and limitations of conventional and alternative IV methods in estimating mean treatment-effect parameters, the role of heterogeneity in comparative effectiveness research and the implications for diffusion of technology.

PMID: 22010051 [PubMed - as supplied by publisher]

Thursday, October 20, 2011

Neuropsychology Abstract of the Day: A SenseCam Study

There is a growing research literature in neuropsychology examining the SenseCam, a relatively long-time Microsoft project.

Microsoft's research project: SenseCam

Here is another example:

The neural correlates of everyday recognition memory
Brain and Cognition. 2011 Aug;76(3):369-81
Milton F, Muhlert N, Butler CR, Benattayallah A, Zeman AZ


We used a novel automatic camera, SenseCam, to create a recognition memory test for real-life events. Adapting a 'Remember/Know' paradigm, we asked healthy undergraduates, who wore SenseCam for 2 days, in their everyday environments, to classify images as strongly or weakly remembered, strongly or weakly familiar or novel, while brain activation was recorded with functional MRI. Overlapping, widely distributed sets of brain regions were activated by recollected and familiar stimuli. Within the medial temporal lobes, 'Remember' responses specifically elicited greater activity in the right anterior and posterior parahippocampal gyrus than 'Know' responses. 'New' responses activated anterior parahippocampal regions. A parametric analysis, across correctly recognised items, revealed increasing activation in the right hippocampus and posterior parahippocampal gyrus (pPHG). This may reflect modulation of these regions by the degree of recollection or, alternatively, by increasing memory strength. Strong recollection elicited greater activity in the left posterior hippocampus/pPHG than weak recollection indicating that this region is specifically modulated by the degree of recollection.

PMID: 21561699 [PubMed - indexed for MEDLINE]

Animal Modelling of Testing Task Switching

This is an open-access, free-download article from the PLoS journal:

Caselli L, Chelazzi L (2011) Does the Macaque Monkey Provide a Good Model for Studying Human Executive Control? A Comparative Behavioral Study of Task Switching. PLoS ONE 6(6): e21489. doi:10.1371/journal.pone.0021489

Article pdf

Wednesday, October 19, 2011

SAGE Therapeutics

A report from Fierce BioTech:

Third Rock Ventures Launches SAGE Therapeutics to Address CNS Disorders with Critical Unmet Needs
Posted October 18, 2011


"Third Rock Ventures, LLC today announced the formation of SAGE Therapeutics. The company was launched with a $35 million Series A financing. SAGE's efforts focus on advancing a broad pipeline of new, critically needed treatments for some of the most disabling central nervous system (CNS) disorders such as schizophrenia, depression, pain and traumatic brain injury (TBI). SAGE Therapeutics is founded on a proprietary Positive and Negative Allosteric Modulator (PANAM) chemistry platform that will enable the rapid development of a novel class of allosteric receptor modulators. Steven Paul, M.D., the former executive vice president for science and technology and president of Lilly Research Laboratories and a former scientific director of the National Institute of Mental Health (NIMH) and Douglas Covey, Ph.D., professor of biochemistry at the Washington University School of Medicine, are founders of the company."


Read the full report