MRI of Recovery from Alcohol Use Disorder

Michal Juhas 2014

MRI of Recovery from Alcohol Use Disorder

INTRODUCTION

MRI of Recovery from Alcohol Use Disorder

Alcohol Use Disorder

AUD is the biggest addiction problem in the developed countries (Nutt et al. 2010) 140+ M people worldwide affected (WHO, 2011)
2.6% of Canadians, 3.5% of Albertans (15+)
(Mayor, 2001; Tjepkema, 2004)

4.5% of global burden of disease (WHO,2011)

causal factor of 60+ diseases

http://www.oag.cz/casak/files/2011/11/homer_drunk.jpg

chronic disorder with limited treatment options alcohol abuse = $3.3 (0.4) billion in direct health care costs and $14.6 (1.6) billion in total social costs in Canada (AB) in 2002
(Rehm et al., 2006)

MRI of Recovery from Alcohol Use Disorder

Nutt, David J., Leslie A. King, and Lawrence D. Phillips. "Drug harms in the UK: a multicriteria decision analysis." The Lancet 376.9752 (2010): 1558-1565.

MRI of Recovery from Alcohol Use Disorder

Lind, T. et al. Developing an Alberta Alcohol Strategy (2007). Government of Alberta. 789A: 11

MRI of Recovery from Alcohol Use Disorder

Effects of Alcohol on Brain

widespread effects on all cells

endocrine and nervous systems interferes with multiple neuronal ion channels, cell membranes, enzymes, and receptors

no alcohol-specific receptor in the brain

alcohol alters the following neurotransmitter systems:

Sober

increased GABA transmission decreased glutamate transmission (NMDA) decreased acetylcholine transmission increased endogenous opioid signalling (betaendorphins) increased DA and 5HT turnover

Intoxicated
http://pubs.niaaa.nih.gov/publications/arh313/233-237.htm

MRI of Recovery from Alcohol Use Disorder

excessive alcohol causes structural and functional changes in the brain

http://pubs.niaaa.nih.gov/publications/arh301/38-47.htm

alcohol and its metabolites (esp. acetaldehyde) are toxic and result in production of reactive oxygen species and inflammation cognitive deficits and regional brain damage is present even in heavy social drinkers (>3drinks/week) with no neurological or hepatic problems (Harper et al. 2009) chronic exposure results in adaptation to compensate for alcohols effects

MRI of Recovery from Alcohol Use Disorder

Chronic Alcohol Abuse

in overall brain volume (WM, GM, CSF/ventricles) WM volume most affected (also FA) neuron density, dendritic arborization & connectivity different neuron populations are more vulnerable correlated to attention, working memory, postural stability, visuospatial ability, decision making etc. switch from positive to negative reinforcement and physiological dependence reinforcement of addiction circuits and brain adaptation increased appetitive drive circuits decreased executive control circuits
http://faculty.washington.edu/chudler/alco.html

MRI of Recovery from Alcohol Use Disorder

Abstinence

prolonged abstinence correlates with clinical improvement

Eijk, Julia, et al. "Rapid partial regeneration of brain volume during the first 14 days of abstinence from alcohol." Alcoholism: Clinical and Experimental Research 37.1 (2013): 67-74.

nonverbal memory, visuospatial abilities, attention, & gait improve in patients after extended abstinence over months (and years)

static balance and other factors remain impaired even after many years clinical improvement correlated with brain regeneration

WM volume, ventricular volume with long term abstinence (evident already at 2 weeks) evidence of adult stem cell neurogenesis some damage seems to be permanent

MRI of Recovery from Alcohol Use Disorder

... Abstinence

http://www.cairn.info/revue-de-neuropsychologie-2013-3-page-187.htm

brain networks appear to be rewired rather than repaired alcoholics recruit different brain regions even after prolonged abstinence these more diffuse networks are less efficient (Nixon et al. 1995) decreased functional connectivity in limbic reward regions and increased in executive control regions (Chamchong et al 2013) even after prolonged abstinence the brain of an addicted person is different from before AUD and must actively compensate for the changes

MRI of Recovery from Alcohol Use Disorder

Functional MRI

http://www2.fmrib.ox.ac.uk/education/fmri/images/boldsmall.gif

MRI of Recovery from Alcohol Use Disorder

Resting State Networks

http://c431376.r76.cf2.rackcdn.com/57176/fnhum-07-00650-r2/image_m/fnhum-07-00650-g002.jpg

MRI of Recovery from Alcohol Use Disorder

RESEARCH PROJECT

MRI of Recovery from Alcohol Use Disorder

Objectives
1. What structural and functional connectivity changes occur in the human brain due to chronic AUD?
Which of these changes are reversible during short term (3-week) recovery? Do these changes correlate with the clinical outcome?

2.

3.

MRI of Recovery from Alcohol Use Disorder

Methods
11 male inpatients with AUD (DSMIV-TR; age 42+/-3); 4 healthy males (age 41+/- 5) performed questionnaire evaluation of addiction, substance abuse, and general state of mind used triple strength 4.7 Tesla Varian MRI Scanner for MPRAGE, fMRI EPI, and DTI scanning scanning sessions 3 weeks apart used custom MatLab code, GIFT, SPM, and xjView for pre-processing and analysis

MRI of Recovery from Alcohol Use Disorder

PRELIMINARY RESULTS

Independent Component #5

MRI & Recovery from Alcohol Use Disorder

Changes in AUD Inpatients after 21 day abstinence (n = 11)

Changes in Healthy People after 21 days (n = 4)

Day 1 Comparison between alcohol dependent & healthy people

Day 21 Comparison between alcohol dependent & healthy controls

MRI &in Recovery from Alcohol Use Disorder Changes in Voxel Intensity ACC (IC5)

MRI of Recovery from Alcohol Use Disorder

Future Work
1. Continue recruitment and verify ICA findings.
Perform seed-based functional connectivity analysis. Perform Voxel-Based Morphometry to compare structural changes. Perform DTI analysis of FA as well as long and short tract tractography.

2.

3.

4.

http://naltrexone.olmifon.net/wp-content/uploads/2012/01/Revia.jpg http://opioids.com/naltrexone/naltrexone.jpg http://scitechdaily.com/images/Crystal-structure-of-the-mu-opioid-receptor-bound-to-a-morphinan-antagonist..jpg https://www.healthcare.siemens.com/siemens_hwem-hwem_ssxa_websites-context-root/wcm/idc/groups/public/@global/@imaging/@mri/documents/image/mdaw/mjew/~edisp/mri-syngo-resolve-dtitractography-00200930/~renditions/mri-syngo-resolve-dti-tractography-00200930~8.jpg

MRI of Recovery from Alcohol Use Disorder

SUMMARY

MRI & Recovery from Alcohol Use Disorder

Research Team
SUPERVISORS: Dr. Serdar Dursun Dr. Andrew Greenshaw Dr. Matthew Brown Dr. Tim Gillese
CLINICAL COLLABORATORS: Marnie MacKay

TREATMENT CENTRES: Henwood Our House Adult Addiction Recovery Centre

STUDENTS: Michal Juhas James Benoit Dr. Ericson Dametto

MRI & Recovery from Alcohol Use Disorder

Acknowledgements

Questions?
juhas@ualberta.ca

780-248-1235