Functional Brain Imaging in the Mouse

Functional magnetic brain imaging (fMRI) provides a new tool for understanding the brain in humans. It is already been helpful in understanding connectivity and focal brain region functions across a variety of domains, i.e. vision, hearing, motor function, somatic sensation and emotional processing. However, functional brain imaging in the mouse model has trailed structural brain imaging development. 

• So why would fMRI be a potentially useful research tool in mice? There are several reasons. Here are some of the key reasons: 
• Mice are easily available and can be repeatedly scanned across time
• Molecular and genetic alterations are available that can perturb (modify) cellular and genetic systems related to brain development and brain function--looking at the fMRI effects of these perturbations would be helpful
• Mouse models are available for a variety of human clinical neuroscience conditions--understanding the effects of these models on brain function could be very helpful.
• It is safer and easier to study drug effects (i.e. anesthetic agents) in the mouse model than in humans

 With these issues in mind, it is exciting to see the recent research summary from Dr. Brian White and colleagues at Washington University in St. Louis in Plos One. Dr. White proposes the method and model for examining fMRI in mice. He summarizes results from fMRI performed in 5 mice using optical intensity signal imaging (OIS). He starts out with one of the simplest fMRI challenges--functional connectivity mapping. This technique uses an imaging model of the resting brain examining correlations between various regions. These correlations suggest connectivity between specific brain regions. A brain with a known specific function, i.e. vision can be assigned a region (or seed) of interest and correlations with that region can be evidence of brain connectivity with the region.

Here is a summary of some of the key findings from the study:

• Mice show left-right symmetrical connectivity (similar to humans) but less anterior-posterior connectivity
• Olfactory, cingulate and frontal regions show connectivity suggesting an intact limbic system network
• A default network appears in the mouse retrosplenial area--this is proposed as early evolutionary component of the human default network that would involve the human dorsolateral prefrontal cortex and the lateral parietal cortex

The authors note fMRI imaging is much less costly than in humans although the estimated cost is not listed in the manuscript. The minimum equipment cost for 3T fMRI in humans in about $3 million with high technical maintenance costs.

So look for expansion of the technology for functional brain imaging in the mouse model. Another example of how man and mouse can work together to better understand the brain and provide insight into the mechanism and potential treatments for clinical neuroscience disorders.

Image of fMRI correlations between regions using 8 different seed regions courtesy of Plos One open access.

White, B., Bauer, A., Snyder, A., Schlaggar, B., Lee, J., & Culver, J. (2011). Imaging of Functional Connectivity in the Mouse Brain PLoS ONE, 6 (1) DOI: 10.1371/journal.pone.0016322

Ethical Challenges in Neuroscience

Dr. Nuala Kenny presented the December 2010 Warren Frontiers in Neuroscience lecture at Laureate Psychiatric Hospital and Clinic in Tulsa, Oklahoma.  Dr. Kenny is a physician trained in pediatrics with a long interest in ethics.  She formed the Department of Bioethics at Dalhousie University in Nova Scotia, Canada.  Her presentation was titled: “Brain, Mind and the Moral: Challenges of Neuroethics”.  Several scientific publications cited in her presentation are referenced at the end of this commentary.  The following are my lecture notes:

Ethics in neuroscience or neuroethics is an important topic given the explosion in basic science as well as clinical research in neuroscience.  The neuroethics field has grown over the last decade.  Despite the development of neuroethics there is no widely accepted definition of the term.

Oklahoma is an appropriate location for a presentation on this topic.  One might say that ethics in neuroscience got started “On the wrong hoof” in Oklahoma.  Dr. Lewis “Jolly” West, the University of Oklahoma chair of Psychiatry in the 1960s performed research funded by the CIA in their portfolio of LSD research and mind control.  Dr. West famously performed an experiment on an elephant where a large bolus of LSD resulted in the collapse of the animal, seizures and death.  Not a great starting point.

Modern bioethics grew in the 1960s based on technological advances in medicine (dialysis, mechanical ventilation, transplantation) and research.  The key initial areas included issues of consent, competence, determining the risk-benefit ratio of treatments and research protocols, and the issue of justice.  Out of this work came the four key principles of medical ethics 1.) autonomy, 2.) beneficence- doing the most good, 3.) non-malfeasance—limiting risk of harm and 4.) justice.  Although these principles are helpful in addressing ethical review on an individual case basis, they do not aid in more global discussion of ethics such as that necessary in neuroscience.

A 2002 conference sponsored by the Dana Foundation in California set out an agenda to “Map the Field” of ethics in neuroscience and identified four key areas of importance—these areas are reviewed with some comments on interval neuroscience research developments:

Therapeutic interventions

• Screening has developed that allows the diagnosis of clinical neuroscience disorders where no treatment is available—how do we wisely use this technology?
• fMRI may be able to identify children and adolescents  at high-risk for developing conditions such as schizophrenia—how should this information be used and discloses
• Treatments such as deep brain stimulation in Parkinson’s disease can dramatically reduce the motor symptoms of the condition, but may result in more disinhibited behavior and reduced decision-making ability.  How do we assess risk-benefit ratios in these types of interventions

Social policy

• Advance imaging techniques provide a wealth of information about the brain and brain function.  Imaging is commonly combined with genetic information for more powerful experiments.  Imaging technology is now available to combine two types of imaging at once (see combined MRI/PET image above). What are the key neuroethical issues involved in these more powerful imaging technologies?
• Cognitive enhancement drug research is underway the can improve concentration, memory and alertness in normal individuals.  What should be the limitations in the use of these drugs—are we devaluing normal human imperfections that define use?

Public education

• Science education is hard and neuroethics education equally hard—How do we best inform the general public on these issues?
• The media have significant power in shaping what the public knows in developing brain science and the ethical implications.  The media loves neuroscience and brain research breakthrough.  Does the media have an interest in a thoughtful discussion of the neuroethics involved in this research?

Implications of neuroscience in self, agency and moral responsibility

• Neuroscience stimulates thoughtful re-analysis of key ethical issues such as the self, agency (authenticity) and moral responsibility.  There is a strong element of neuroreductionism in some neuroscience research, i.e. “ I am what my neurons and synapses are doing”.  We need to be careful about this approach and the tendency for mind-brain dualistic thinking
• Neuroscience is focusing on how the brain makes ethical and moral decisions.  This reversal challenges ethicists to stay up-to-date on functional MRI and other brain imaging research advances in decision making, variability in processing ethical information, lying and cognitive control in psychopathological behavior.

Brain Posts Comment:  This presentation does highlight some of the key ethical challenges for basic and clinical neuroscientists.   There will need to be emphasis on public education in neuroethics and continuing study and discussion of neuroethical implications as imaging technology is more widely implemented.  You can learn more about the topic of neuroethics at this Dana Foundation website.

Image of combined PET and MRI scans from unrestricted public domain image by author Mco44.  

West LJ, Pierce CM, & Thomas WD (1962). Lysergic Acid Diethylamide: Its Effects on a Male Asiatic Elephant. Science (New York, N.Y.), 138 (3545), 1100-3 PMID: 17772968

Leentjens AF, Visser-Vandewalle V, Temel Y, & Verhey FR (2004). [Manipulation of mental competence: an ethical problem in case of electrical stimulation of the subthalamic nucleus for severe Parkinson's disease] Nederlands tijdschrift voor geneeskunde, 148 (28), 1394-8 PMID: 15291423


Young L, & Saxe R (2009). An FMRI investigation of spontaneous mental state inference for moral judgment. Journal of cognitive neuroscience, 21 (7), 1396-405 PMID: 18823250


Tairyan K, & Illes J (2009). Imaging genetics and the power of combined technologies: a perspective from neuroethics. Neuroscience, 164 (1), 7-15 PMID: 19409220