The Brain in Super Agers

My Twitter post on a recently published study of brain structure in a group of high performing older adults received quite a bit of attention (see below).

Felicia Sun and colleagues at Massachusetts General Hospital and Harvard Medical School selected an interesting research design.

A group of elderly subjects between the ages of 60 and 80 years were identified as showing "superaging". This was defined as scoring like young adults on two neuropsychological tests: The Long Delay Free Recall measure of the California Verbal Learning Test and part B of the Trail Making Test.

They then imaged the brain structure and function of the super agers using MRI. The results were compared to two groups: elderly adults without superior cognitive performance and younger adults with age-typical neuropsychological performance.

A key finding from their study was that super agers had brain hippocampal volumes greater than typical older adults and this measure was comparable to young adults.

Super agers also had greater brain volumes than typical older adults in the following regions:

• Anterior temporal cortex
• Medial frontal cortex
• Anterior midcingulate cortex

The authors noted in the discussion section:

"We found support for our hypothesis regarding the structural integrity of the default mode and salience networks, with superagers showing much less atrophy than typical older adults in key nodes of these networks, which we refer to as the "superageing signature".

The authors also note their longitudinal study was not able to identify the factors that may play a key role in super agers. Candidate factors include genetic factors, exercise, diet and social activity levels. These factors are likely to be studied in future research.

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

Figure of hippocampus is an iPad screen shot from the app 3D Brain.

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"Study suggests how 'super aging' older adults retain youthful memory abilities" #neuroscience #feedly https://t.co/DdlXUGbRRp

— W.R.Yates, M.D.✍ (@WRY999) September 14, 2016

Sun FW, Stepanovic MR, Andreano J, Barrett LF, Touroutoglou A, & Dickerson BC (2016). Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging. The Journal of neuroscience : the official journal of the Society for Neuroscience, 36 (37), 9659-9668 PMID: 27629716

Gambling and Brain Frontal-Striatum Connections

For the remainder of 2015, Brain Posts will focus on pathological gambling and also highlight the top-viewed posts for the year.

Functional connectivity is a relatively recent brain imaging technique that provides a new look at brain circuitry at rest and with tasks.

Resting state connectivity using fMRI provides a snapshot of brain connections in each individual. There is increasing study of resting connectivity in individuals with disorders in neuroscience medicine compared to control populations.

Saskia Koehler and colleagues in Germany recently published a study of resting fMRI connectivity in a group of problem gamblers and controls.

Problem gamblers (PG) in this study were recruited via advertisement on the internet and posted notices in casinos. PB was assigned based on a questionnaire for problem gambling that included DSM-IV and ICD-10 diagnostic criteria.

The key findings in the PG compared to the controls included:

• Increased connectivity in PG between the right middle frontal gyrus and the right striatum
• Decreased connectivity in the PG between the right middle frontal gyrus and other prefrontal regions
• The right ventral striatum region showed enhanced connectivity to the right middle and superior frontal gyrus and the left cerebellum

The striatum is a brain region known to be linked to the reward system. The authors note in the introduction:

"Immediate reward seeking behavior has been linked to regions of the mesolimbic system, since subcortical areas such as the ventral striatum (including the nucleus accumbens) are highly active during reward processing."

It makes sense that individuals with PG show hyperactivity between brain executive decision-making regions (frontal cortex) and the brain reward regions of the striatum. The fact that these increased hard-wiring effects can be seen at rest supports the strength of the brain connectivity finding. 

The study also found correlations between the frontal-striatum hyperactivity and two psychometric measures assessed in the study: nonplanning impulsivity and gambling craving subscores.

The increased connectivity between the right frontal cortex and the striatum have been previously demonstrated in substance abuse. In the current study, alcohol intake and cigarette use were match in PG and control to address potential confounding addiction variable effects.

The authors note their study supports research into therapies (psychotherapy and drugs) that target frontal-striatum connectivity in developing innovative interventions in PG.

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

Figure in this post is an original photo with impressionism filter from the author's files. Photo may be reproduced with link to the site.

Follow the author on Twitter: WRY999 

Koehler S, Ovadia-Caro S, van der Meer E, Villringer A, Heinz A, Romanczuk-Seiferth N, & Margulies DS (2013). Increased functional connectivity between prefrontal cortex and reward system in pathological gambling. PloS one, 8 (12) PMID: 24367675

Parenting Moderates Childhood Brain Stress Response

Child brain development benefits from a positive parenting style and environment.

The mechanism for this positive effect is unclear but moderation of the stress response in the growing child is an area of research interest.

Haroon Sheikh and colleagues from the University of Ontario in Canada recently published results on a study of parenting and brain development in children.

In their study, a cohort of 46 six year old girls underwent brain imaging using a technique known as diffusion tensor imaging or DTI. DTI provides a measure of brain white matter integrity.

This study is informative because all the girls participated in an earlier study of stress reactivity at three years of age. High stress reactivity as measured by serum cortisol response is known to be linked to vulnerability to mood and anxiety disorders.

The key elements in the design of this study including the following:

• Subjects: 45 six year old girls from a larger ongoing longitudinal study of children
• Stress response status: At three years of age participants underwent a two phase study of stress response. A baseline salivary cortisol assay was collected. A second cortisol level was obtained during a stressful task. Subjects were grouped in four categories based on levels of cortisol.
• Parenting assessment: Parents and child participated in a play task. Parents were rated on a measure of parental negative and positive affect.
• MRI scanning: A 3 Telsa brain imaging scan was completed on average two and one-half years following the baseline cortisol and parenting assessment

The main findings from the study included the following:

• High stress reactivity at baseline was linked to lower white matter integrity in prefrontal and basal brain regions (left thalamus, right anterior cingulate cortex and right superior frontal gyrus)
• Positive parental affectivity reduced the brain white matter effects of stress (cortisol) response in the right anterior cingulate cortex and right superior frontal gyrus
• Children with high stress responses at baseline but a positive parental affect environment showed brain integrity findings similar to low stress reactivity children

This is an important study because it suggests an interaction between parental environment and adverse effects of a high stress response in three year old girls. Genetic factors likely contribute to level of stress response in three year old girls. A positive parental style appears to reduce or eliminate adverse effects of high stress reactivity on critical white matter brain development.

The implications of the study are important. High-risk children for mood and anxiety disorders may benefit from early identification and parental training to reduce risk for later psychological morbidity.

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

Photo of hawk in flight is from the author's files.

Follow the author on Twitter @WRY999

Sheikh HI, Joanisse MF, Mackrell SM, Kryski KR, Smith HJ, Singh SM, & Hayden EP (2014). Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting. NeuroImage. Clinical, 6, 77-85 PMID: 25379418

Real-Time fMRI Psychotherapy

Old World Psychotherapy: Sofa of Sigmund Freud

There has been a series of interesting research studies examining the effect of psychotherapy on brain structure and function.  These studies have typically shown that effective psychotherapy results in reduction of brain deficits or abnormalities associated with a specific neuropsychiatric disorder.

Now a study published in Plos One summarizes the results of study examining the use of real-time fMRI to provide neurofeedback during an amygdala activation task.

This research was completed by neuroscientists affiliated with the Laureate Institute of Brain Research in Tulsa, Oklahoma and George Mason University in Fairfax, Virginia. (Disclosure: The author of Brain Posts is employed by Laureate Institute of Brain Research but was not involved in the study reviewed in this post.)

The authors of this study noted the key role of the amygdala in the processing of emotions.   They developed a experimental paradigm to train control subjects to increase the activation of the brain left amygdala.  A group of young male subjects were instructed in a happy autobiographical memory task and provided real-time feedback on how successful they were in increasing blood flow to the left amygdala.

Subjects identified three key happy memories from their past.  During the experimental phase, they were instructed to recall these specific memories while being scanned using an fMRI scanner. They were provided real-time feedback on a monitor screen on the changes in left amygdala BOLD signal.  (Subjects were told prior to scanning that fMRI neurofeedback is delayed by a few seconds due to the brain hemodynamic process).

Subjects provided real-time feedback were more successful at increasing the left amygdala activation than those in a control group.  This increase in the experimental group correlated with increases in other brain areas known to have functional connectivity with the amygdala (fronto-temporo-limbic network).

New World Psychotherapy: Real Time fMRI

Additionally, the study identified six specific regions where functional connectivity identified correlations with the left amygdala activation:

• right medial frontal cortex
• bilateral dorsomedial prefrontal cortex
• left anterior cingulate cortex
• bilateral superior frontal gyrus

Subjects were selected based on being free of a history of neuropsychiatric disorders including anxiety and depression.  However, there was some variability in the level of change in left amygdala activation with neurofeedback training.  Subjects who scored high on the Difficulty Identifying Feelings scale had less increase in the left amygdala.  Additionally, subjects with higher scores on a scale of being susceptible to anger showed less increase.

This research is an very important advance in understanding the amygdala and regions connected with the amygdala.  Additionally, it raises the possibility that real-time fMRI may emerge as a tool to understand processes associated with psychotherapy and to be an emerging model for providing therapy under real-time neurofeedback conditions.  

The site of psychotherapy might be moving from the sofa model of Sigmund Freud to the fMRI scanner.  Both methods have subjects that lie down, but only the fMRI method provides real-time feedback of brain effects related to a psychotherapy intervention.

The authors note that this study was a type of "proof-of-concept" study since it focused on healthy control subjects.  They suggest that this type of model might be particularly relevant to cognitive behavioral treatment of conditions such as PTSD and major depression.

Photo of Sigmund Freud sofa from the Freud Museum in London from Wikipedia distributed under the GNU Free Documentation License.


Photo of Functional Magnetic Research Imaging device courtesy of the Laureate Institute for Brain Research. 

Zotev, V., Krueger, F., Phillips, R., Alvarez, R., Simmons, W., Bellgowan, P., Drevets, W., & Bodurka, J. (2011). Self-Regulation of Amygdala Activation Using Real-Time fMRI Neurofeedback PLoS ONE, 6 (9) DOI: 10.1371/journal.pone.0024522

Common Brain Anatomy Features in Autism and Schizophrenia

Neuropsychiatric disorder classification challenges clinicians and researcher alike.  Classical approaches have used a distinct non-overlapping categories approach.  Increasingly, research suggests that distinct disorders share clinical and neuroanatomical features.  This means that it might be possible for specific genes and environmental effects to produce more than one disorder.

Cheung et al from the University of Hong Kong, China explored brain structural commonalities between autism and schizophrenia.  Using a novel statistical classification strategy, MRI data were compared in a group of 308 subjects with autism, 352 with first-episode schizophrenia and 801 controls.  The strategy group anatomical differences into those found in autism alone, schizophrenia alone and in both autism and schizophrenia (figure).

The authors used a series of imaging data sets to perform their analysis.  The autism group included several clinical groups including autism, Asperger’s and high-functioning autism.  The schizophrenia group were all first-psychotic episode with some being antipsychotic naïve and some with a history of antipsychotic drug exposure.

The figure from the manuscript shows the grouping for various brain regions grouped by frontal/parietal region/temporal lobe-basal ganglia region and cerebellum.   Both diagnostic groups demonstrated gray matter reductions in the right posterior cingulate, the right parahippocampal gyrus, putamen and left thalamus. 

Subjects with schizophrenia demonstrated many more local regions of atrophy not found in autism including the right and left superior and medial frontal gyrus, right and left cingulated and left insula, caudate, temporal gyrus and amygdala.  The only unique site of gray matter atrophy for the autism group was the left putamen.

The authors note that these two disorders are “indicative of overlapping neuroanatomical phenotype” but do not imply that autism and schizophrenia are a “common entity”.  The authors conclude: “Our findings should therefore encourage further exploration of the potential shared etiologies and better understanding of the mechanisms separating the 2 conditions”.

I think you will see increasing research examining commonalities between what have up until now been considered distinct conditions.  Look for more evidence that distinct disorders have significant phenotype overlap.  Examining these shared features may provide a better understanding of the pathophysiology of a variety of mental disorders.

Figure Provided from PloS One Manuscript

Cheung C, Yu K, Fung G, Leung M, Wong C, Li Q, Sham P, Chua S, & McAlonan G (2010). Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation. PloS one, 5 (8) PMID: 20805880