Weight Training Boosts Brain Size and Performance

Aerobic exercise increases brain blood flow and has demonstrated beneficial effects on cognition.

The effects of weight training exercise on the brain is less frequently studied. Hence, we know little about the effect and mechanism of weight training on brain function and performance.

A recent study provides some needed insight on this topic.

A study by C Suo and colleagues from Australia examined the effects of resistance training and cognitive skills training on brain structure and function.

The key elements of design in their study included the following features:

• Subjects: 100 elderly subjects of average age 70 years with mild cognitive impairment
• Intervention: 6 months of progressive resistance training (PRT), computerized cognitive training (CCT), both interventions or neither intervention (sham control group)
• Cognitive assessments: MMSE, Clinical Dementia Rating Scale and a battery of neuropsychological tests
• Imaging: Pre- and post- 3T MRI voxel-based quantitative assessments of brain regions and resting state fMRI
• Statistical Analysis: SPSS linear mixed model studying three main effects, time, PRT and CCT

The findings in this study were quite remarkable:

• PRT: Increased performance on global cognition
• PRT: Increased brain gray matter volume in the posterior cingulate cortex (see image)
• PRT: Increase in cigulate gray matter volume correlated with improvement in global cognition
• PRT: Reversed progression of brain white matter intensities, a biomarker of cerebrovasular disease
• CCT: Slowed progression of decline in overall memory performance
• CCT: Enhanced connectivity between brain hippocampus and superior frontal cortex

This is one of the first studies finding a significant improvement in cognitive function in elderly subjects after progressive resistance training.

Additionally, the study supports PRT's potential benefit in reversing brain white matter intensities (WMI). I have previously written a blog post on the association of WMI with increased rates of dementia and premature death. You can find that post HERE.

The take home message here is that both PRT and CCT appear to have beneficial effects on slowing the effects of aging on the brain. They each appear to have unique mechanisms and brain targets. A smart preventative program for brain health in the elderly would combine the two interventions.

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

Image showing cingulate cortex is an iPad screen shot from the app 3D Brain

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Suo C, Singh MF, Gates N, Wen W, Sachdev P, Brodaty H, Saigal N, Wilson GC, Meiklejohn J, Singh N, Baune BT, Baker M, Foroughi N, Wang Y, Mavros Y, Lampit A, Leung I, & Valenzuela MJ (2016). Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise. Molecular psychiatry, 21 (11) PMID: 27090304

Robin Williams and Lewy Body Disease

In a post last week, I highlighted a recent study examining clinical issues in the diagnosis of Lewy body dementia (LBD).

This study examined differentiating clinical and neuropsychological factors between LBD, Alzheimer's dementia and Parkinson's disease.

You can access this post by clicking HERE.

This topic received significant attention following the description of comedian Robin Williams' last years by his wife in the journal Neurology.

Robin Williams suffered from LBD and like many, his diagnosis was not made until autopsy.

I want to review some of the key clinical features shown by Robin Williams described by his widow's in his last few years.

Psychological symptoms/signs

• Anxiety
• Fear 
• Panic attacks
• Depression
• Paranoia
• Delusions
• Suicide

Cognitive symptoms/signs

• Memory impairment
• Fluctuating levels of memory/orientation

Physical symptoms/signs

• Constipation
• Urinary problems
• Heartburn
• Insomnia
• Poor sense of smell
• Sensitivity to anti-psychotic medications
• Tremor left hand
• Freezing of gait

Lab/Imaging

• Elevated serum cortisol levels
• Normal brain imaging (CT or MRI?)

Neuropathology

• 40% loss of dopamine neurons
• Lewy bodies throughout brain
• High concentration of Lewy bodies in brain amygdala

A clinical diagnosis of Parkinson's disease had been made for Robin and he had been placed on anti-Parkinson's medication. 

Signs and symptoms of LBD as outlined by Mayo Clinic staff  include:

• Visual and other hallucinations
• Movement disorder (signs of Parkinson's disease)
• Autonomic nervous system dysregulation (tachycardia, sweating, constipation, dizziness, falls)
• Cognitive problems (confusion, visuospatial problems, memory loss, fluctuating levels of attention)
• Sleep problems (REM sleep behavior problems)
• Depression/Apathy

As noted in Mrs. Williams' description, Robin Williams never reported visual hallucinations, a key symptom in LBD.  However, his clinical team felt is was quite possible visual hallucinations could have been present and simply not disclosed due to fear of how others would perceive the hallucinations.

The high concentration of Lewy bodies in the brain amygdala could explain some of the panic, fear and depression noted in the case history.

Suicide is not commonly noted in LBD although it has not been studied in great detail. I will examine this issue in a separate post.

Mrs. Williams has done a great service in writing this clinical history. She urges increased research into the causes and treatment for LBD. Additionally, her report again underscores the need for clinicians to be vigilant for the signs and symptoms of LBD.

I highly recommend reading about the clinical history of Robin Williams. You can access the free full-text report by clicking HERE.

Access the Mayo Clinic description of Lewy body dementia by clicking HERE.

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Photo of Robin William's Hollywood star is from a Creative Commons Wikipedia file authored by:
CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=2710421

Williams SS (2016). The terrorist inside my husband's brain Neurology, 87 (13), 1308-1311

Statin Therapy: Rethinking Benefits and Risks

A recent 30-page manuscript provides an exhaustive review of the evidence for the efficacy and safety of statin therapy.

The authors of this excellent review provide some context for the relative value of statins.

The note that putting 10000 individuals with a history of a vascular event on a statin drug for 5 years would prevent 1,000 subsequent events. This is an example of secondary prevention--preventing another adverse outcome in those already experiencing an adverse event.

But the statin drugs also appear very powerful in primary prevention-preventing a first event in those at high risk for vascular disease. They estimate putting 10,000 individuals at high risk for vascular events on statins would result in prevention of 500 vascular events over five years.

This review provides an up-to-date review of the safety of statins and generally supports the therapy as very low risk.

One proposed adverse event of statin therapy is concern about memory and cognition. However, the authors note that well-designed studies of statin therapy in older individuals find no evidence of adverse cognitive effects compared to placebo.

They argue that:

"..given the weight of evidence against adverse effects of statin therapy on memory or other adverse effects of cognition, it would now be appropriate for regulatory authorities to consider removal from the lists of potential adverse effects on the drug labels so that patients are not inappropriately deterred from using statin therapy." (emphasis mine).

The authors go on to emphasize the potential adverse public health consequences of misleading claims regarding the safety of the statin drug class.

This excellent review is likely to lead to further discussion about extending the indications for statin use in the general population.

This review also supports discussion between individuals and their physicans on the appropriateness of statin therapy as part of a disease prevention progra.

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

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Photo of osprey in flight is from my photography files.

Collins R, Reith C, Emberson J et al.  (2016). Interpretation of the evidence for the efficacy and safety of statin therapy Lancet : http://dx.doi.org/10.1016/S0140-6736(16)31357-5

Mediterranean Diet and Cognition

The evidence for a beneficial effect of a Mediterranean style diet (MedDiet) on brain health grows on a regular basis.

For those interested in a good summary of the effects of the MedDiet on cognition, I recommend reading the free full text review recently published in Frontiers in Neuroscience.

In this review, Roy Hardman and colleagues searched for research studies on cognition and the Mediterranean diet published between 2000 and 2015.

A figure in the review proposed several mechanisms where components in a MedDiet may contribute to brain function:

• Cardiovascular: effect on blood pressure/blood lipids and arterial stiffness
• Inflammation: lowering of blood inflammatory markers including C-reactive protein and cytokines
• Neurotrophic effects: Increased levels of BDNF, insulin growth factor stimulating neurogenesis
• Cell signalling
• Cellular energy metabilism
• Lowering of oxidative stress

Using a rigorous selection process, Hardman and colleagues identified 18 high-quality recent studies of the MedDiet and adult human cognition. These studies generally demonstrated an positive effect for subjects with higher compliance with MedDiet elements. These positive effects included research supporting:

• A slower rate of cognitive decline with aging
• A reduced risk of developing mild cognitive impairment
• Improved recognition memory and delayed recognition memory
• Improved cognitive reserve on the Mini-mental status examination test (MMSE)
• Improved attention

The authors conclude that evidence to date supports prospective randomized clinical trials of MedDiet nutritional intervention. These studies should included standardized batteries of cognitive function that can be administered via a computer or tablet.

For readers with more interest in the review, you can access the free full-text manuscript by clicking on the PMID link in the citation below.

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Photo in this post of foods found in the Mediterranean diet is from my personal files.

Hardman RJ, Kennedy G, Macpherson H, Scholey AB, & Pipingas A (2016). Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A Qualitative Evaluation and Systematic Review of Longitudinal and Prospective Trials. Frontiers in nutrition, 3 PMID: 27500135

The Brain: Red Meat and Mediterranean Diet

Entorhinal Cortex Highlighted in Blue

Previous posts in this blog have highlighted some the research related to links between brain health and elements of the Mediterranean diet.

I want to inform readers of a new important research study from the Mayo Clinic.

In this study, researchers completed brain cortical thickness analyses on 672 cognitively normal adults. It is generally accepted that greater cortical thickness relates to improved cognitive performance.

The participants completed an extensive dietary history and brain cortical thickness measures were correlated to total and component Mediterranean diet intake. Here are the key findings from the study:

• Higher Mediterranean diet total scores were linked to greater cortical thickness measures in frontal, parietal, occipital and total brain
• Higher legume and fish component intake had the highest links to greater cortical thickness
• Legume intake correlated with greater cortical thickness in parietal, precuneus, occipital and lingual regions
• Fish intake correlated with greater precuneus, parietal and posterior cingulate cortical thickness
• Carbohydrate intake was linked to lower entorhinal cortical thickness
• Red meat intake correlated with greater entorhinal cortical thickness

This study in important for several reasons. First, it highlights specific components (legume and fish) of the Mediterranean diet with thicker brain cortices.

But what I found most interesting was the red meat finding.  Red meat intake was associated with slightly smaller cortices in two parietal regions. However, this association did not reach statistical significance. The association of red meat intake with greater entorhinal cortex thickness did reach statistical significance. 

The authors note some of the epidemiological research linking red meat intake to increased rates of dementia. This made their finding of a positive entorhinal cortex finding with red meat intake unexpected and they note in discussion section:

"The potential mechanism is unclear; we speculate that it could relate to some beneficial components of lean read meat (e.g. iron, protein, MUFA and PUFA) and beneficial effects on increasing satiety and reducing weight gain."

The entorhinal cortex is a key brain region serving as a link between the hippocampus and neocortex. The Wikipedia description of the role for the entorhinal cortex includes important contributions to:

• declarative memory
• spatial memory
• memory consolidation
• memory optimization in sleep

This study is observational in nature and shares weakness with this type of research design. The findings will need replication. Nevertheless, the study suggests fish, legume and lean red meat intake may contribute to preservation of brain cortical health.

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Image is an iPad screen shot of the entorhinal cortex from the 3D Brain app.

To access the study abstract, click on the PMID link below.


Staubo SC, Aakre JA, Vemuri P, Syrjanen JA, Mielke MM, Geda YE, Kremers WK, Machulda MM, Knopman DS, Petersen RC, Jack CR Jr, & Roberts RO (2016). Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness. Alzheimer's & dementia : the journal of the Alzheimer's Association PMID: 27461490

Elite Cyclists and Brain Fatigue Resistance

In a Brain Post from 2012 I reviewed a study of fatigue in elite athletic performance. This study supported a key role in the brain insula in regulating the perception of exercise-induced fatigue. You can access this post by clicking HERE.

An update on this topic was recently published in PloS One by a research team in Australia.

This study compared performance on a cognitive task after extreme 20 minute cycling time trial. Professional cyclists were compared to recreational cyclists on the Stroop test that requires inhibitory control.

The results of the study were that elite cyclists performed significantly better on the Stroop test (more correct responses) following exercise than non-elite cyclists. This is indicative of a greater resistance effects of fatigue on brain performance.

The authors note in the discussion section:

"These finding suggest that successful endurance performance may require superior inhibitory control and resistance to mental fatigue."

This resistance to mental fatigue at high levels of exercise may be a key component in successful performance at the elite level.

Inhibitory control has been shown to have a significant genetic association and to be stable over time. It is possible that training interacts with genetic factors to produce brain fatigue resistance in the elite cyclist population.

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

Follow the author on Twitter HERE.

Photo of non-elite cyclist participating in triathlon is from the author's files. 


Martin K, Staiano W, Menaspà P, Hennessey T, Marcora S, Keegan R, Thompson KG, Martin D, Halson S, & Rattray B (2016). Superior Inhibitory Control and Resistance to Mental Fatigue in Professional Road Cyclists. PloS one, 11 (7) PMID: 27441380

Aging and Cognition: Free eBook Resource

Yesterday I posted on Twitter a link to a post on the Dana Foundation website.

In this post, they reviewed highlights from a seminar on cognitive aging sponsored by the American Association for the Advancement of Science (AAAS).

There is a YouTube video of the seminar that I will be reviewing in the next few days and will likely write up a summary of my notes from the video.

One important item I picked up was the recommendation of a free PDF book titled:
Cognitive Aging: Progress in Understanding and Opportunities for Action.

You can access this free aging and cognition book resource by clicking HERE.

The link to the Dana Foundation post is HERE.

Follow me on Twitter (@WRY999) HERE.

Mediterranean Diet and Alzheimer's Disease Prevention

There is an urgent need to identify strategies to prevent or delay the onset of Alzheimer's disease and other forms of dementia.

The role of diet as a prevention strategy is controversial. Some research evidence supports a role for a Mediterranean diet in cognitive health and dementia prevention.

A recent brain imaging study adds to this evidence. Dr. Lisa Mosconi and colleagues at New York University School of Medicine completed a cross-sectional study of brain magnetic resonance imaging and diet was completed in 52 older cognitively normal individuals.

The key elements of the design of this study were:

• Subjects: Community subjects participating in a longitudinal brain imaging study with a mean age of 54 years (standard deviation 12 years). Approximately 2/3 of the subjects were women.
• Study measures: Dietary information was collected using the Harvard/Willet food frequency questionnaire and subjects were rated on adherence to a Mediterranean diet using the MeDi. This scale rates intake of fruit, vegetables, legumes, cereal and fish as beneficial with dairy and meat intake rated detrimental. Information on dietary fat and alcohol were also used rated for a nine-item Mediterranean diet score. Subjects scoring greater than 5 were rated as Mediterranean diet adherent. 
• Brain imaging: All subjects completed a cross-sectional brain MRI using a 1.5 Tesla scanner. Volumetric brain measures were calculated using FreeSurfer software.
• Statistical analysis: Multivariate general linear modeling was used to assess the correlation of diet (high vs low Mediterranean diet adherence) with correction for a variety of potential confounding variables including age, gender, family history of Alzheimer's disease, APOE gene status and BMI.

The brain analysis focused on regions of the brain known to show atrophy with Alzheimer's dementia. 

This analysis showed Mediterranean diet adherent subjects with statistically significant greater brain thickness measures in the left brain hemisphere for:

• entorhinal cortex
• orbitofrontal cortex
• posterior cingulate cortex

This effect was found in the uncorrected volumetric data and the relationship remained with correction for age and total intracranial volume measures.

The authors note previous brain imaging studies have linked cognitive decline and dementia with atrophy of the left hemisphere regions of the brain found significantly linked to Mediterranean diet adherence in this study.

An additional brain area of atrophy in Alzheimer's is the hippocampus a region not addressed in the current research study.

The take home message here is that this study:

"provides support for further exploration of dietary behavior as a possible AD (Alzheimer's disease) prevention strategy".

The sample size is this study is relatively small and will need replication in other larger sample sizes. 

There was no correlation with neuropsychological scores and Mediterranean diet in this study. This is not surprising as the subjects were recruited as being cognitively normal.

It will be interesting to see in the longitudinal follow up if Mediterranean Diet adherence relates to neuropsychological performance and brain atrophy over time.

Readers with more interest in this research can find the free full-text manuscript by clicking on the PMID link in the citation below.

Photo of macaw is from the author's files.

Follow the author on Twitter @WRY999.

Mosconi L, Murray J, Tsui WH, Li Y, Davies M, Williams S, Pirraglia E, Spector N, Osorio RS, Glodzik L, McHugh P, & de Leon MJ (2014). Mediterranean Diet and Magnetic Resonance Imaging-Assessed Brain Atrophy in Cognitively Normal Individuals at Risk for Alzheimer's Disease. The journal of prevention of Alzheimer's disease, 1 (1), 23-32 PMID: 25237654

Exercise and the Brain: Research Links

I am posting links to some of the most recent research related to exercise effects on the brain.

These come from a process of selecting posts to examine in more detail this month.

Clicking on the links will take you to the PubMed abstract. Most of the abstracts also have free full text links.

Enhancing brain activity through multidisciplinary interventions in the elderly

This Chinese study examined the effects of cognitive training, Tai Chi exercise and counseling on a group of 17 elderly individuals compared to controls. The study examined brain low frequency fluctuations and found improved intrinsic activity in the intervention group for the middle frontal gyrus, superior frontal gyrus and anterior cerebellum. The study noted the value of a group intervention for increasing social support ratings.

Single episode of exercise changes resting state brain networks

This study examined the effects of a 20 minutes of moderate intensity aerobic exercise on resting state connectivity of the brain using functional MRI. Exercise produced significant changes from baseline in several brain regions and connections suggesting a valid model for testing the brain effects of acute exercise.

Dietary and lifestyle guidelines for prevention of Alzheimer's disease

This manuscript summarizes results of an expert consensus guideline on prevention of Alzheimer's disease. The experts recommended the equivalent of 40 minutes of brisk walking three times per week.

Physical activity, inflammation, and volume of the aging brain

This longitudinal study in older adults measured self-reported physical activity and a marker of inflammation known as tumor necrosis factor alpha (TNF-alpha). Greater levels of physical activity and lower levels of TNF-alpha (lower inflammation) were correlated with less brain atrophy. 

The effects of chronic exercise on attentional networks

This study examined the correlation between physical activity levels and performance on a task of attention in healthy young adults. The authors found support for exercise as a potential therapeutic modality to improve attention in health young adults.

Photo of sunset at South Padre Island, TX from the author's files.

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Exercise in the Prevention of Alzheimer's Disease

Growing evidence links physical activity to improved cognitive outcome in elderly individuals.

Few studies have examined effects of exercise on those at highest risk for Alzheimer's disease.

J Carson Smith and colleagues recently published a prospective study of a cohort of older adults using structural magnetic resonance imaging.

The key elements of the design of their study included the following elements:
Participants: 97 adults between the ages of 65 and 89
Physical activity level: Frequency and intensity of leisure activity was assessed using the Stanford Brief Activity Survey
Alzheimer's risk status: Assessed using APOE genotype
Brain scanning protocol: Magnetic resonance imaging of brain using a 3T scanner at baseline and 18 months later. The brain hippocampal volume was identified as a key structure involved in APOE-related atrophy and memory decline
Statistical analysis: Participants were grouped in low and high physical activity groups and those with and without high-risk APOE Alzheimer's risk

The research team identified a statistically significant interaction between high-risk Alzheimer's participant and physical activity:

"Hippocampal volume decreased 3% in the High Risk/Low PA (physical activity) group whereas the volumetric changes in the remaining three groups were negligible."

The high-risk Alzheimer's group that participated in higher levels of physical activity appeared to have significant protection against hippocampal atrophy. To reach the higher levels of physical activity in the study they had to endorse one of the following levels:

• Brisk walking 15 minutes daily three or more days per week
• Jogging 15 minutes daily three or more days per week
• Swimming 15 minutes daily three or more days per week
• Moderately difficult chores 45 minutes daily three or more days per week
• Regular jogging, running, bicycling or swimming 30 minutes or more
• Playing sports such as handball or tennis an hour or more 

The authors examine the potential mechanisms for physical activity to reduce hippocampal atrophy in those with the high risk APOE genotype.

They note the beneficial effect of exercise may be through effects on cholinergic function, brain lipid metabolism or reduced neuroinflammation.

If this study is replicated it is an important finding with several implications.

One implication is that it may be one of the first research findings to support routine genetic testing for APOE and Alzheimer's risk. Those identified as high risk by APOE status could be targeted for aggressive behavioral interventions to increase physical activity along with increased surveillance of cognitive function.

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

Follow the author on Twitter WRY999

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

Smith JC, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Hazlett KE, Figueroa CM, Kandah CC, Kay CD, Matthews MA, & Rao SM (2014). Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease. Frontiers in aging neuroscience, 6 PMID: 24795624

Are Athletes Better Performers Outside Sport?

Marlins Mike Stanton Rounds Third Base After Homer

Performing at the highest level in many sports requires the development of a complex group of cognitive, fine motor, gross motor, eye-hand coordination and fitness skills.

These multiple skill domains are often performed in a emotionally-charged environment where multi-tasking.  Think a baseball batter monitoring signals from coaches, remembering a pitcher's preference for pitches in certain situation and performing on the road where a sell out crowd roars with each pitch.

This batter then need to use visual skills, timing and motor skills making a swing that where he hopes to land at least a base hit.

A sports exercise research team recently as a good research question related to this type of sport specific skill: "Do athletes perform better in non-sport \tasks that also require quick action and multitasking?

Laura Chaddock and a research team from the University of Illinois recently published online the results of their study in the journal Medicine & Science in Sports & Exercise.  The authors wanted to know if athletes with specific sport training would be able to perform a non-sport physical activity better than non-athletes.

To do this they developed a real-life virtual reality task of quickly and safely crossing a two-way street.  This paradigm requires a special facility and involves manual treadmills, computer simulation of traffic and wireless liquid crystal goggles that provide a sense of depth perception and movement.

The athlete group in the study include 18 University of Illinois participating in NCAA intercollegiate athletics (two baseball, one cross-country runner, one gymnast, two soccer players, five swimmer's, three tennis players, one track-and-field athlete and three wrestlers.  Athletes spent average of 20 hours per week practicing their college sport. Nonathlete controls were not involved in an athletic activites organized by the University of Illinois.

Athletes and controls completed three separate trials--one with no distraction, one while talking on a cell phone and one trial while listening to music through an iPod.

Both groups also completed a simple reaction time task using a desk top computer.

Here were the key results of the study:

• Athletes successfully crossed the street within a 30 second time limit 75% of the time with no distraction compared to only 56% in the non-athlete controls (statistically significant with p<.05)
• Athletes also were more successful under both distraction trials
• Athletes were less likely to be involved in a pedestrian collision during a simulation (23% vs 39% for non-athlete controls
• Athletes reaction time was significantly less than non-athlete controls and this variable negatively correlated with street crossing success rates (individuals with slow reaction times had lower success rates)

The authors note that their cross-sectional study cannot address causality.  One explanation for the results is that sport training provides improvements in reaction time and other psychomotor performance variables that translate to other non-sport multitasking setting.  An second possible explanation is that those with an innate psychomotor skill advantage perform better in athletics and other performance situations like the one found in this street-crossing simulation.  

It is also possible that both of the proposed explanations contribute something to this effects.  

This study also made me think about the effect of age-related reduction in reaction time and the performance in real-world street crossings and other potentially dangerous situations.  This type of simulation could be used in research related to this topic.

Photo of Mike Stanton homering against Chicago Cubs from the author's collection.


Chaddock, L., Neider, M., Voss, M., Gaspar, J., & Kramer, A. (2011). Do Athletes Excel At Everyday Tasks? Medicine & Science in Sports & Exercise DOI: 10.1249/MSS.0b013e318218ca74

Man as Social Animal: TED talk of David Brooks

David Brooks has been a political journalist for the New York Times for many years.  Recently he has developed an interest in cognitive neuroscience and the importance of social factors in philosophy and human life.  Here are my notes from his 18 minute recent TED talk:

Politicians are all "emotional freaks" of one variety or another

They have a "logodementia"--Talk so much they drive their self insane

But they do have exceptional social skills

Mitt Romney anecdote--able to remember names of everyone he met in the diner

However, in making political decisions this social skill is of little assistance

We have made little progress in education

People learn from people they bond with emotionally

Why are politicians dehumanized when talking about policy?

We have pushed out emotion in making decisions about our lives

We have lost the ability to understand the importance of character and we have lost the ability to talk about using our social intelligence

We pressure our children to jump through competitive hoops

We don't emphasize the importance of developing a philosophy of life

Cognitive neuroscience is providing insight into a new way of thinking about life:

1.) The unconscious mind does most of the work--The unconscious mind is quite smart

2.) Emotions are at the center of our thinking (Antonio Dimasio speaking on this issue later in the TED program)--Brain is a record of our entire life feelings

3.) We are deeply social animals-our brain and thinking are connected to those around us

How do we see human capital?

Reason is often week, sentiments are strong and trustworthy

For humans to thrive humans need:

Mind sight--ability to see into the minds of others and understand their thinking (ability to attach to other versus an avoidant att

Equipoise--having the serenity of analyze are our own biases

Street Smarts--ability to pattern recognize and 

Sympathy--the ability to work in groups on common task--group effectiveness not affected by 

Blending--using diverse view points to blend a new way of thinking

Limericks- unconscious mind hungers for moments of transcendance--these moments occur in relationships with our closest relationships

David has a NY Times bestseller book in this topic area: The Social Animal.  I have not read the book and so can not comment on it's merit.  It is on my future reading list as soon as a copy is available at my local public library.

What Do Antidepressants Do in Healthy Brains?

The easiest answer to the title question is “cause side effects”.  A more important theoretical and practical aspect of this question is: Do antidepressants have a general property experienced by everyone or are their effects only seen in the presence of depression?  Antidepressant drugs have research support for a variety of non-depression indications including: chronic pain, fibromyalgia, migraine prophylaxis, irritable bowel syndrome and pathological crying and laughing.  So there are quite a few non-depressed individuals taking antidepressants making the title question is important.

Serretti and colleagues from Italy recently summarized published research on this issue.  Additionally, they performed some meta-analyses when appropriate to look for effects across studies.   They note the review suggests that antidepressant effects in the normal or healthy brain may be different under acute than under chronic treatment.   They authors conclude there is some evidence that antidepressants increase social behaviors and reduce negative effects in the healthy brain.  They structure their review based on antidepressant class and I will note the highlights of their paper by class.

Studies of Selective Serotonin Reuptake Inhibitors (SSRIs)

The selective serotonin reuptake inhibitors (i.e fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro)) are the most commonly prescribed class of antidepressants.   SSRIs do not reduce sub-threshold symptoms of anxiety or depression as measured by the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI).  They do tend to reduce negative affect as measured by the Positive and Negative Affect scale.  In addition, SSRIs do reduce the amount time spent in REM sleep in healthy individuals.  The clinical implication of this is unknown. Escitalopram appears to decrease activation in several fMRI tasks with some evidence for decreased activation of the amygdala compared to baseline activation.

Studies of Norepinephrine Reuptake Inhibitors (NRIs)

This class of drug is represented by reboxetine, an antidepressant not found in the United States.  The drug atomoxetine (Strattera) used for attention deficit hyperactivity disorder (ADHD) is sometimes assigned to this class of compound.  A single dose of reboxetine appears to influence social behavior by increasing cooperativeness in communication, reducing focus on self and reduced anxiety ratings.  It also appears to enhance recognition of positive environmental stimuli such as processing happy facial expressions and positive words.  Some of these effects persist over at least one or two weeks.  Brain imaging studies show reduced amygdala responses to fearful faces.

Studies of Serotonin and Norepinephrine Reuptake Inhibitors (SSNRIs)

This class of agents includes the compounds venlafaxine (Effexor), desvenlafaxine (Pristiq) and duloxetine (Cymbalta).   There are many fewer studies involving these agents as researchers tend to often one to focus a single neurotransmitter.   A single dose study of duloxetine demonstrated showed enhanced recognition of both happy and sad faces.  Early responses to these compounds tend to reflect transient side effects rather than a specific brain response in healthy individuals. 

Other agents: Noradrenergic and specific serotenergic antidepressants (NaSSAs), tricyclic antidepressants, monoamine oxidase inhibitors

This miscellaneous class would include mirtazapine (Remeron), amitriptyline (Elavil), and phenelzine (Parnate).  Mirtazapine appears to have some sedative side effects in healthy individuals and along with amitriptyline (and other tricyclics) have the potential to impair psychomotor performance including driving performance.  Tricyclic antidepressants also (like SSRIs) share the ability to reduce REM sleep duration in healthy individuals.

The authors conclude that this review tends to confirm that the human response to antidepressants is similar to the response in rats.  Early exposure to antidepressants tends to increase anxiety but over time anxiety behaviors tend to decrease to below baseline.  Early anti-depressant exposure reduces socializing behaviors in rats but increases them in the long term.   There are very few human studies that have been carried out for more than a week or two.  This means the long-term effect of exposure to antidepressants agents is unknown.


The brain imaging data suggest that antidepressants influence emotional experience and processing in healthy individuals.  There is a variety of individual variation in emotional experience and processing, but the antidepressants appear to move healthy individuals along this domain.

One interesting aspect of this issue is that we know very little about the comparison of side effect patterns in non-depressed individuals.  Do healthy controls experience the same type of side effects to the same degree as depressed individuals?  We have a wealth of data comparing side effects of antidepressants compared to control within depressed populations.  But the volume of data comparing side effects between depressed individuals and non-depressed is small.

Molecular model of the antidepressant escitalopram (Lexapro) courtesy of Creative Commons author Ben Mills.

Serretti A, Calati R, Goracci A, Di Simplicio M, Castrogiovanni P, & De Ronchi D (2010). Antidepressants in healthy subjects: what are the psychotropic/psychological effects? European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 20 (7), 433-53 PMID: 20079613

Brain MRI White Matter Intensities: Clinical Significance

T2 White Matter Hyperintensity (Mild left, Extensive right)

Novel imaging findings emerge with the advancement of imaging techniques.  Commonly, the meaning of new imaging findings is unknown until further clinical research provides answers.  This situation describes the finding of white matter intensities on brain magnetic resonance imaging.  White matter intensities are relatively common in the aging brain as well as with a variety of clinical disorders.  Two manuscripts provide new insight into the clinical significance of this MRI finding.

Debette and Markus performed a metanalysis of the existing literature through November 2009 in a BMJ article published in early 2010.  Their study examined 46 longitudinal studies.  Often, when first discovered, white matter intensities occur in the context of relatively normal brain function.  But these lesions are not normal as they indicate an increased risk for the following outcomes (estimated as relative risk increases)

• Increased risk of stroke 3.5 (350% increase)
• Increased risk of dementia 1.9 (90% increase)
• Increased risk of death 2.0 (100% increase)

The Debette and Markus review noted that there was some support for white matter hyperintensities to be linked to neuropsychological deficits like global cognitive decline, impaired executive function and decreased processing speed.

The neuropsychological effects of white matter intensities is the subject of a manuscript by Murry and colleagues from the Mayo Clinic.  This study examined a total of 148 elderly (73-91 years of age) subjects with white matter intensities on MRI but without current dementia.  The subjects underwent a battery of neuropsychological tests.  Additionally, the specific brain region for the white matter hyperintensities was examined in relationship to cognitive performance.  The primary findings from this study were:

• Lower executive function was found with these lesions for all areas except for occipital white matter hyperintensities (executive function including planning and complex decision making skills)
• White matter hyperintensities (particularly parietal lobe) were correlated with Parkinson's disease scores for impaired gait, posture and postural stability)
• Higher white matter intensities in all regions except the occipital regions as well as subcortical and periventricular regions correlated with slowed visuomotor performance (Trail Making Test Part B) and reduce gait (walking) speed

So this study adds two important elements to understanding white matter intensities.  First location makes a difference and second, white matter intensities should not be just noted to be present or absent but an estimation of the burden (volume) of the lesions is informative.  This study also helps to quantitate the effect of white matter intensities on risk for Parkinsonian symptoms. 

Murray and colleagues conclude: "The selective nature of the functional deficits associated withWMHsuggests thatthe primary effect of WMH is to reduce the efficiency of neuronal signaling. This conclusion is strengthened by the fact that vastly different functional domains—cognition and gait—were affected, with the common theme being processing speed.

White matter MRI images from the BMJ 2010:341:c3666 an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

Debette, S., & Markus, H. (2010). The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis BMJ, 341 (jul26 1) DOI: 10.1136/bmj.c3666

Murray, M., Senjem, M., Petersen, R., Hollman, J., Preboske, G., Weigand, S., Knopman, D., Ferman, T., Dickson, D., & Jack, C. (2010). Functional Impact of White Matter Hyperintensities in Cognitively Normal Elderly Subjects Archives of Neurology, 67 (11), 1379-1385 DOI: 10.1001/archneurol.2010.280