Early Birds, Night Owls and Working Memory

There is a growing body of research showing the individual preference for mornings or evenings influences human performance and disease.

Early birds is common term for individuals who arise early and prefer activity in mornings. Night owls often stay up late at night and find they are more productive in the evenings.

This day time preference pattern is known scientifically as chronotype.

Christina Schmidt and colleagues from Belgium recently published an interesting study of the effect of chronotype on working memory and brain activity.

The key elements of their research design included the following elements:

• Subjects: 32 young healthy volunteers with 16 showing a morning chronotype and 16 showing a evening chronotype
• Procedures: Subjects participated in a series of studies involving sleep diaries, polysomnography in a sleep lab and neuropsychological testing. Working memory was tested using a procedure known as the N-Back Paradigm.
• Brain imaging: Subjects completed functional magnetic resonance imaging in a 3T MRI scanner. Brain regional patterns of activation were analyzed during working memory tasks. Individual performance and activation patterns were compared between a morning scan and and evening scan.  Morning preference individuals were compared to evening preference individuals.

The main findings from the study included the following:

• Subjects performed modestly better on the most complex working memory task based on their chronotype--morning individuals performed better in the morning and evening individuals performed better in the evening
• During evening imaging, evening preference individuals demonstrated higher memory task activation of the brain thalamus than morning preference individuals
• During morning imaging, morning preference individuals demonstrated higher memory task activation of the middle frontal gyrus than evening preference individuals

The authors note that one implication of their study is the need to measure chronotype preference in neuropsychological testing and functional brain imaging. Chronotype preference is a potential confounding variable in memory and other cognition studies.

Additionally, this study shows that brain correlates of peak performance do appear to depend on time of day. Morning preference types appear to perform best in the morning and might want to arrange their most demanding cognitive tasks in the morning. The opposite is true for evening chronotypes.

So for example, if you are an evening chronotype, you might want to consider taking a memory-intensive task, i.e. the SAT exam as late in the day as possible.

Individuals with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.

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Schmidt C, Collette F, Reichert CF, Maire M, Vandewalle G, Peigneux P, & Cajochen C (2015). Pushing the Limits: Chronotype and Time of Day Modulate Working Memory-Dependent Cerebral Activity. Frontiers in neurology, 6 PMID: 26441819

ADHD Clinical Trial Research: Reading Links

In the upcoming week I will be reviewing a few recent clinical trials in ADHD.

Here are a few of the studies that caught my eye as recent and important research.

Clicking on the title will take you to the research abstract and for some studies a link to the free full-text manuscript.

Behavioral treatment for sleep problems in children with ADHD

Sleep problems are a common contributing factor to the clinical profile in ADHD. In this study, 244 children with ADHD received a standard behavioral intervention target at sleep hygiene. Children receiving the sleep intervention had improved ADHD symptoms at 3 and 6 months following the intervention.

In-school neurofeedback training for ADHD

This study examined the effects of neurofeedback, cognitive therapy and control intervention in a group of 104 children with ADHD. The study found superior sustained response to neurofeedback compared to response to cognitive therapy or the control intervention.

Eszopiclone for insomnia in ADHD

This study was a randomized double-blind placebo-controlled trial of 1 and 2 mg of eszopiclone (Lunesta in U.S.) for treatment of insomnia in children with ADHD. The study failed to find a therapeutic effect for the drug in reducing time to sleep using sleep studies (polysomnography).

Edivoxetine in children with ADHD

Edivoxetine is an investigational drug that has selective norepinepherine reuptake inhibition. This randomized controlled study found evidence for efficacy in ADHD in children and adolescents between 6 and 17 years of age.

Methylphenidate enhances cognitive performance even in the absence of an ADHD diagnosis

This study looked at the effects of methylphenidate (Ritalin in the U.S.) in individuals with weak cognitive performance but no ADHD diagnosis. This group of individuals showed improvement in working-memory and sustained attention tasks. This study suggests stimulants may have a more general role in the treatment of cognitive deficits.

I was struck by the relatively few number of well-designed intervention studies published in ADHD over the last year. This is discouraging as the disorder is prevalent, has a high burden of suffering and desperately needs new treatment approaches.

Photo of roseate spoonbill is from the author's files.

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Fitness, Hippocampus and Forgetting

Hippocampus in Green from 3D Brain iPad App

Cardiorespiratory fitness appears to be associated with a variety of benefits in cognitive functioning.  The mechanisms for this benefit are unclear.  Association studies do not provide evidence for the pathways between related variables.  For understanding pathways, clinical trials, longitudinal studies and multivariate approaches are more powerful approaches.

Amanda Szabo and colleagues at the University of Illinois at Urbana-Champaign recently published a multivariate study looking at fitness, hippocampus and forgetting in a group of elderly adults in the journal Neuropsychology.  The hippocampus is a brain region known to crucial to working memory.  Changes in hippocampal volume have been linked to age-related cognitive decline and the development of Alzheimer's disease.

The key elements of design in this study included:
Subjects: 158 older adults with a mean age of 66.5 years
Variables: Fitness level as measured by VO2 estimate from a graded exercise test, brain hippocampal volume from a brain 3T MRI scan, spatial working memory task, subjective rating of forgetfulness (Frequency of Forgetting Questionnaire)
Statistics: Path analysis examining direct and indirect effects of fitness on hippocampal volume, working memory test performance and subject rating of forgetfulness using the comparative fit index (CFI)

The authors started with a presumed pathway model for the mechanism of the relationship between fitness and forgetfulness in the following pathway:

• fitness levels predict hippocampal volume
• hippocampal volumes predicts working memory function performance
• working memory performance predicts subjective forgetfulness

Fitness levels were associated with a variety of sociodemographic and medical variables at baseline including: self-reported physical activity, presence of hypertension, cardiovascular disease, body mass index, education level, gender and age.  These baseline variables were evaluated and controlled in the final pathway analysis.

The authors found their predicted model held up in the analysis: "cardiorespiratory fitness is associated with the frequency of forgetting indirectly through its influence on hippocampal volume and, in turn, spatial working memory".

The study noted fitness level is not the sole determinant of hippocampal atrophy.  Age alone is an independent contributor of hippocampal atrophy.  Fitness may reduce the effects of age-related hippocampal atrophy and forgetfulness but it is unable to reverse the effect.

So fitness is not a panacea but it appears to be an important factor in maintaining cognitive function in later life.  Now, I just wonder if my wife can help me find my running shoes?

3D Brain image of the hippocampus in green screen shot from the author's collection.

Szabo, A., McAuley, E., Erickson, K., Voss, M., Prakash, R., Mailey, E., Wójcicki, T., White, S., Gothe, N., Olson, E., & Kramer, A. (2011). Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults. Neuropsychology, 25 (5), 545-553 DOI: 10.1037/a0022733

Test Anxiety and Working Memory Impairment

Anxiety related to test performance appears to affect a significant number of individuals.  The prevalence of test anxiety in school children has been estimated as up to 15% to 20%.  Some studies have found the prevalence higher in girls than in boys--this would be consistent with the gender prevalence patterns found in other childhood anxiety disorders.

Children with test anxiety show educational assessment levels approximately 1/2 standard deviation below their nonanxious peers.  This translates into approximately a 12 percentile difference in these two groups.

In the U.S. there is increased emphasis on improvement in standardized testing performance with scrutiny of individual teacher and school performance effects.  Any intervention that would potentially increase performance in a subgroup of students (i.e. those with text anxiety) could be an important intervention in raising testing scores.

However, the effect of interventions on test anxiety on test performance is unclear.  Well-designed large-scale test anxiety interventions are limited.  Better understanding of the relationship between test anxiety and neuropsychological performance is needed.

Gass and Curiel recently published a study of test anxiety and neuropsychological performance in a group of adult veterans.  Two hundred and eighty six veterans referred for neuropsychological testing completed a comprehensive neuropsychological inventory known as the Halstead-Russell Neuropsychological Evaluation System-Revised (HRNERS).

Subjects were grouped by level of test anxiety related to response of a inventory known as the Test Anxiety Profile (TAP). Groups were then compared on a variety of neuropsychological domains with the following key results:

• High TAP scores more commonly found in those with lower levels of educational attainment (years of education)
• High TAP scores correlated with decreased performance on working memory performance
• High TAP scores did not correlate with impairment in processing speed, verbal comprehension, perceptual organization or overall neuropsychological test index performance

The authors note these findings suggest relatively intact neuropsychological performance in adults with self-reported test anxiety.  Neuropsychological testing appears valid even in those who report problems with test anxiety.

The findings also suggest that test anxiety may be a consequence rather than a cause of working memory impairment.  The direction and meaning of the correlation remains unclear.  If test anxiety is a consequence of reduced working memory, there may be limited change with interventions that target reducing test anxiety.

One problem with interpretation of the Cass and Curiel study is the age of the study population.  The mean age of subjects was 59.3 years of age.  Participants were long past the time of their formal educational period.  How well their rating of test anxiety correlated with actual test anxiety during their school years is unknown.

More detailed research of the correlates of test anxiety and neuropsychological performance in children and adolescents is needed.  These types of studies might suggest more effective interventions for improving cognitive performance (and standardized testing) in our schools.

Photo of Juno Beach, Florida sunrise from author's collection.

Gass CS, & Curiel RE (2011). Test anxiety in relation to measures of cognitive and intellectual functioning. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 26 (5), 396-404 PMID: 21636602