an mr spectroscopy examination of brain metabolites in autism€¦ · an mr spectroscopy...
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An MR Spectroscopy Examination of Brain Metabolites in Autism
Rajesh K. Kana, Ph.D.
UAB CAS Interdisciplinary Team Proposal Presentation Alumni Auditorium (April 16, 2013)
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Dr. Adrienne Lahti Dr. Nouha Salibi
Lauren Libero Meredith Reid Rishi Deshpande David White
Interdisciplinary Research Team
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Brain Imaging
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Autism: Triad of Impairments
SOCIAL INTERACTION
AUTISM
American Psychiatric Association (1994)
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Where in the brain is Autism located?
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A B
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MR Spectroscopy (1H-MRS)
NAA
Glx
Cho
Cr
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The molecular structures of 6 brain metabolites commonly studied with 1H-MRS
Maddock & Buonocore (2012); Curr. Topics in Beh. Neur.
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N-Acetyl Aspartate
• Amino acid synthesized in mitochondria of neurons
• Marker of neuronal integrity
• Robust signal in 1H-MRS studies
• Correlates with cognitive function
NAA
11
Glx
Cho
Cr
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Glutamate/Glutamine
• Glutamate is the major excitatory neurotransmitter
• Direct precursor for GABA, the major inhibitory neurotransmitter
• Glutamine synthesized from glutamate in astrocytes & broken down to glutamate in neurons
• Complex 1H-MRS spectra
Glx
12
NAA
Cho
Cr
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TD
ASD
Subdivisions of the Human Cingulate Cortex
Hong et al. (2009); JAMA Psychiatry Beckman et al. (2009); J. Neuroscience
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Dorsal Anterior Cingulate
• Part of a functional network • Works together with DLPFC • dACC involved in both monitoring &
control • dACC also has a role in reward-based
decision making • Specific mechanisms not well
understood • No theory fully explains the
cognitive/emotional division
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Posterior Cingulate Cortex
• Part of the Default mode Network (DMN)
• Self-reflection and Autobiographic memory (Spreng et al., 2009)
• Visuospatial orientation and navigation of the body in environmental space (Vogt & Laureys, 2005)
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• A series of sagittal, coronal, and axial T1-weighted anatomic scans serving as MRS-localizers (TR/TE = 250/3.48 ms, flip angle = 70°, 5 mm slice thickness, 1.5 mm gap, 512 x 512 matrix) will be acquired for spectroscopic voxel placement. The MRS voxel will be placed in a region of the bilateral ACC and PCC
• Manual shimming will be done to optimize field homogeneity across the voxel, and chemical shift selective (CHESS) pulses will be used to suppress the water signal.
• Spectra will be acquired using the point-resolved spectroscopy sequence (PRESS; TR/TE = 2000/80 ms, number of averages = 256 (scanning time = 8 min 32 s), voxel size 2.7 x 2 x 1 cm3). MRS data will be analyzed in jMRUI (www.mrui.uab.es/mrui) (Naressi, 2001).
MRS Data Acquisition & Analysis
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Reduced NAA Level in dorsal ACC in Autism
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Correlation between NAA level and Dorsal ACC activation in Autism
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40
60
80
100
120
140
160
180
200
1.25 1.3 1.35 1.4 1.45
RAADS
NAA
r = -0.51
40
60
80
100
120
140
160
180
200
1.4 1.45 1.5 1.55 1.6
RAADS
NAA
r = -0.64
The Ritvo Autism Asperger Diagnostic Scale
Dorsal ACC PCC
Symptom severity and Neurochemical Level
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No Group Difference in NAA levels in PCC
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Reduced Glutamine/Glutamate level in dorsal ACC in Autism
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1015202530354045505560
0.5 0.6 0.7 0.8 0.9
Empathy
r = 0.62 r = 0.82
Dorsal ACC PCC
1015202530354045505560
0.02 0.04 0.06 0.08
Empathy
Glutamate/Glutamine Glutamate/Glutamine
Correlation between Empathy Quotient & Glx in Autism
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• Patterns of neurochemical alterations in ASD may suggest differences in tissue chemical composition OR neuronal integrity
• Plan to continue data collection and correlating MRS measures with different brain and behavioral findings
• Findings will be presented at the Society for Neuroscience (SfN) Annual Meeting, 2013 and at the International Meeting for Autism Research (IMFAR), 2014
• NIMH R01 proposal submission : June 2013 Cycle
Summary & Future Plans
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UAB College of Arts & Sciences Interdisciplinary Innovation Award Funding Support
Lab: www.uab.edu/cbra
Co-investigators & Collaborators � Adrienne Lahti, M.D. (UAB)
� Nouha Salibi, Ph.D. (Auburn University)
� Lauren Libero
� Keya Kuruvilla
� Rishi Deshpande
� Meredith Reid
� David White