Showing posts with label brain imaging. Show all posts
Showing posts with label brain imaging. Show all posts

Thursday, January 31, 2013

Neuroscience of Human Attachment

Attachment is the ability to form human relationship bonds.  Individuals vary in their ability to develop social relationships.  The ability to form secure human relationships plays a key role in successful personal and occupational development.

Attachment theory evolved over 50 years ago.  This theory proposes all humans have an innate biological mechanism that supports social engagement.  This engagement is necessary during infancy to encourage nurturance and provision of a safe environment.

Bowlby is credited with describing attachment theory and he proposed three developmental styles of attachment.  These three attachment styles included:

  • Secure attachment: an ability to easily seek and obtain support from others.  This style promotes strong bonds with parents, siblings, friends and later in life allows for bonding with a mate.
  • Anxious attachment: a insecure attachment style where emotional support has often been inconsistent during childhood.  Individuals with anxious attachment develop hypersensitivity to interpersonal rejection and have anxiety in social environments.  They may develop a needy approach to relationships constantly seeking reassurance of the strength of social supports.
  • Avoidant attachment: an insecure attachment style that may have been characterized by early social adverse environments.  Individuals with insecure attachment style built a wall around their life denying a need or interest in human interactions.

Emerging research in social neuroscience is providing a better understanding of brain mechanisms related to human attachment.  Vrticka and Vuilleumier of the University of Geneva in Switzerland recently published an excellent review of the neuroscience of human attachment in the journal Frontiers in Human Neuroscience.

The authors of this review begin by noting research showing attachment has profound effects in the domains of emotion processing, selective attention and memory.  Insecure attachment individuals are hypersensitive to changes in the expression of emotions in others.   Anxious attachments individuals have enhanced attention to threatening cues.  Avoidant attachment individuals inhibit the memory processing of distressful information.


The authors note social approach behavior appears regulated in specific brain regions including the ventral tegmental area, pituitary, striatum and ventral medial orbitofrontal cortex.  Social aversion appears to be regulated through the amygdala, hypothalamus, insula, anterior cingulate and anterior temporal poles.

Social behavior appears to regulated through both affective evaluation (emotional mentalization) and cognitive control systems (cognitive mentalizations).  These systems interact with hormonal and neurotransmitter domains in influencing social interactions.

The neuroscience of human attachment includes emerging research showing the importance of mental state representation of others (theory of mind).  Mothers with high sensitivity to the cries of their own infants during the post partum period show increased gray matter and fMRI BOLD responses in the prefrontal cortex, superior temporal sulcus and fusiform gyrus.  These regions have been identified as key components engaged in being aware of the emotional states of others.

The authors conclude that the neuroscience of human attachment is beginning to outline key common and distinct elements in avoidant and anxious attachment styles.  Attachment styles appear to be influenced by both environmental history as well as neurobiological factors, some of which may have strong genetic contributions.

Future neuroscience of research will need to move experiments into the "real world" and not be limited to task in brain scanners.  Additionally, future research needs to target early intervention studies in children with attachment problems to find the most effective methods to improve social outcomes.

Readers with more interest in this review are directed to the DOI link below where the free full text manuscript can be found.

Photo of great white egret from the author's files.

Vrtička, P., & Vuilleumier, P. (2012). Neuroscience of human social interactions and adult attachment style Frontiers in Human Neuroscience, 6 DOI: 10.3389/fnhum.2012.00212

Friday, January 11, 2013

Brain MRI and Enhanced Alzheimer's Drug Trials

Clinical research trials in Alzheimer's disease are hampered by insensitive outcome measures.

This effect results in the need for very expensive large sample sizes trial protocols.

Current state-of-the-art Alzheimer's trials frequently use the Minimental Status Exam (MMSE) or the cognitive subscale of the Alzheimers disease assessment scale (ADAS Cog).  These measures are imperfect and imprecise, often requiring a minimum of 200 to 300 subjects to be enrolled.

One strategy to improve Alzheimer's disease clinical trial methodology is to use more sensitive brain imaging markers to measure therapeutic response.

Ai-Ling Lin and colleagues from the University of Texas Health Science Center at San Antonio have recently reviewed the clinical research literature on this topic (citation below).  They reviewed research studies on cognitive decline using a number of brain imaging techniques including:

  • High-resolution magnetic resonance imaging (MRI)
  • Diffusion tensor imaging (DTI)
  • Functional MRI (fMRI)
  • Cerebral blood flow estimation using arterial spin labeling MRI (ASL-MRI)
  • Single-photon emission computed tomography (SPECT)
  • Magnetic resonance imaging spectroscopy
  • Positron emission tomography (PET)

Obviously, there are many imaging tools available as potential biomarkers in Alzheimer's disease.  A key research issue is to find the most sensitive tool (or set of tools) that is valid and financially feasible.

The review covers research findings related to brain imaging markers in cognitively normal adults with genetic markers for Alzheimer's disease (APOE gene), mild cognitive impairment, the conversion of mild cognitive impairment to Alzheimer's disease and those diagnosed with Alzheimer's disease.  For the purpose of this post I will focus on their findings in those who have Alzheimer's disease.

Alzheimer's disease produces a marked increase in the volume of global and focal brain atrophy.  They note in their study the relative magnitude of yearly brain volume reduction in the 70 to 80 year age group in Alzheimer's disease compared to those without Alzheimer's disease (controls).  The data from high-resolution MRI studies show:
  • Yearly global atrophy rate: 2 to 3% in Alzheimer's disease, 0.3% to 0.5% controls
  • Yearly hippocampus atrophy rate: 3.0 to 5.9% in Alzheimer's disease, 1.0% to 1.7% in controls
  • Yearly entorhinal cortex: 7.2% to 8.4% in Alzheimer's disease, 1.4% to 2.9% in controls

The entorhinal cortex region is a key region in assessing Alzheimer's disease related brain atrophy.  The entorhinal cortex region is highlighted in the figure on the left in blue.


Brain changes in Alzheimer's disease are also found in the default mode network assessed by MRI functional connectivity imaging and in cerebral blood flow using ASL-MRI.

The authors conclude that multimodal MRI (high-resolution MRI, functional connectivity MRI and arterial spin labeling MRI) holds promise as a powerful strategy to measure therapeutic effects in experimental drug study clinical trials for Alzheimer's disease.  They note these techniques will require validation against currently used primary outcome measures.  

However, because of the sensitivity of multimodal MRI, clinical trials may be able to reduce sample sizes to only about 20 to 25 subjects.  

This enhancement would be a big leap in Alzheimer's drug research and development.  It holds the promise of speeding up the clinical trial process and allowing for the study of more potential therapeutic compounds.

Photo of fire-tufted barbet from the San Diego Zoo is from the author's files.

Entorhinal cortex figure is a screen shot from the iPad app 3D Brain.

Lin AL, Laird AR, Fox PT, & Gao JH (2012). Multimodal MRI neuroimaging biomarkers for cognitive normal adults, amnestic mild cognitive impairment, and Alzheimer's disease. Neurology research international, 2012 PMID: 21949904