- Email: [email protected]
Cerebral MRI of human brain development: Ages 4–18
SATURDAY, MAY 20
tions in dopaminergic synaptic markers. The apparent defect in the ability of the high affinity cocaine recognition site to "upregulate" in the ED subgroup suggests a diminished capacity for dopamine reuptake that may "kindle" cocaine psychosis with repeat patterns of "binge" use. Hypothalamic D1 and D2 receptors have opposing effects on thermoregulation, with the D1 receptor mediating a prevailing increase in core body temperature, while D2 receptors mediate a compensatory decrease. While haloperidol is typically used to control agitated delirium, the D2 receptor blockade in the hypothalamus may adversely contribute to the development of the malignant hyperthermia in cocaine psychosis. (Supported by DA06227 and DA9484.)
227. LIMITATIONS OF FMRI STUDIES OF LIMBIC ACTIVATION D. Servan-Schreiber l, D. Noll l, J. Cohenn2, O. Tereshko t, V. Ho 1, D. Swanson I, & J.J. Mann 3 ~Clinical Cognitive Neuroscience Laboratory, University of Pittsburgh Medical Center, Pittsburgh, P A 15213; 2Department o f Psychology, Carnegie Mellon University, Pittsburgh, PA; 3New York Psychiatric Institute, N e w York, NY Specific technical problems arise when using blood oxygenationweighted MRI to document activation of limbic structures within individual subjects. In contrast to sensory, motor, or cognitive stimulation procedures, emotional stimulation is typically of progressive onset and offset and difficult to maintain. In addition, limbic structures such as the amygdala and orbital frontal cortex are h~cated near large air cavities that result in signal voids due to spin dephasing in T2-weighted images and commonly produce edge artifacts due to subtle head movements that can easily be misinterpreted as "'activation." We have used a bite-bar procedure and image realignment to minimize edge artifacts, a selection of slice orientation and thickness that minimizes signal wilds, an image reconstruction technique that corrects for distortions due to magnetic field nonuniformity, subtraction of MR angiograms to eliminate spurious activation from blood vessels, a new statistical procedure relying on clustering of pixels to maximize power, and five different emotional activation procedures, including drug challenges with IV yohimbine and IV procaine. We observed large subjective and physiological changes, and statistically significant areas of activation with every procedure. Time--series graphs of MR signal changes suggest a strong correlation with stimulus changes; however, we believe that extreme caution is necessary in interpreting such results because of significant problems with motion artifacts, and unreliability of activation areas across studies in the same subjects and across subjects with the same stimuli. Additional development and testing of activation paradigms and of MR technique appear necessary before fMRI can be used reliably to study activation of limbic structures.
228. EFFECTS OF AMPHETAMINE IN MAJOR DEPRESSIVE DISORDER USING FUNCTIONAL MRI M.H. Trivedi, T. Blackburn, S. Lewis, R. McColl, R. Peshock, A.J. Rush, & B. Grannemann University o f Texas Southwestern Medical Center at Dallas, Dallas, TX 75235 Major depressive disorder (MDD) has clear biological underpinnings. PET and SPECT have provided evidence of abnormal CNS function al-
BIOL PSYCHIATRY 657 1995;37:593-683
though resting state findings are often inconsistent. Amphetamine challenge paradigm combined with in vivo functional brain imaging provides a method to evaluate the function of specific anatomical regions in depression. Both the nigroslriatal and the mesolimbic dopamine pathways have been extensively examined as sites of amphetamine action. Functional MRI (fMRI) uses high-speed, rapid-imaging MR systems to produce "motion pictures" of changes in blood flow perfusion and volume and accomplishes high resolution and characterization of sequential activation of brain regions over time. Deoxyhemoglobin serves as a contrast to measure cerebral blood flow/volume reflecting increased neuronal activity over the study period. The purpose of this research is to map activation of multiple regions throughout the human brain during a pharmacological challenge. Echo Planar fMRI studies were performed using a Picker Vista 1.5T magnet with a single axis bipolar gradient insert using a quadrature head coil. T2* weighted gradient echo image sets (TE 40 msec, 100 x 105 image matrix, FOV 25-30 cm, 66 msec/slice, minimum 20 slices) were obtained over the entire brain over 80 minutes following amphetamine (0.4 mg/kg PO) in six patients with DSM-III-R MDD and six age-matched normals (NC). Three-dimensional functional maps were produced from difference images. Signal intensity changes of 4%-12% were observed in multiple regions of activation during amphetamine challenge, in the substantia nigra, hippocampal/amygdala, and thalamic regions and their prefrontal connections bilaterally. The regions of activation distinguished MDD from NC subjects. (Funded in part by NARSAD (MHT) and MH4 1115 (AJR).)
229. CEREBRAL MRI OF HUMAN BRAIN DEVELOPMENT: AGES 4-18 J.N. Giedd, F.X. Castellanos, J.C. Rajapakse, D. Kaysen, A.C. Vaituzis, Y.C. Vauss, S.D. Hamburger, & J.L. Rapoport Child Psychiatry Branch, NIMH, Bethesda, M D 20892 Cerebral MRI scans of 105 healthy children and adolescents, ages 4-18, were analyzed to assess the effects of age and gender on the sizes of the cerebrum, cerebellum, caudate, globus pallidus, putamen, thalamus, cerebellum, and lateral ventricles in normal development. Significant gender effects were noted for several structures. Males had a 10% larger cerebral and 7% larger cerebellar volume, which remained statistically significant after correction for height and weight (p < 0.001 ). After adjusting for total cerebral volume, putamen and globus pallidus remained larger in males, while caudate volume was larger in females. Cerebral volume as a whole did not change significantly across this age span; however, cerebellar volume increased 18%. In males only, caudate and putamen decreased with age (p = 0.007 and 0.004, respectively). Lateral ventricular volume increased for both genders (p = 0.0007 for males, 0.05 for females), with males showing a significant increase in slope after age 11 (p = 0.03). For cerebral hemispheres and lateral ventricles, there was a significantly greater left than right asymmetry (p = 0.0001 and p = 0.02, respectively). In contrast, caudate and globus pallidus showed a greater right than left asymmetry (p < 0.001 ). The volumes of all structures demonstrated a high degree of natural variability. Females exhibited significantly larger variability than males, after correcting for age, height, and weight effects, for all structures except the globus pallidus (equal variability) and cerebellum (less variability). These findings highlight the need for relatively large gender-matched samples in developmental brain morphometric studies of normal and clinical populations.
tions in dopaminergic synaptic markers. The apparent defect in the ability of the high affinity cocaine recognition site to "upregulate" in the ED subgroup suggests a diminished capacity for dopamine reuptake that may "kindle" cocaine psychosis with repeat patterns of "binge" use. Hypothalamic D1 and D2 receptors have opposing effects on thermoregulation, with the D1 receptor mediating a prevailing increase in core body temperature, while D2 receptors mediate a compensatory decrease. While haloperidol is typically used to control agitated delirium, the D2 receptor blockade in the hypothalamus may adversely contribute to the development of the malignant hyperthermia in cocaine psychosis. (Supported by DA06227 and DA9484.)
227. LIMITATIONS OF FMRI STUDIES OF LIMBIC ACTIVATION D. Servan-Schreiber l, D. Noll l, J. Cohenn2, O. Tereshko t, V. Ho 1, D. Swanson I, & J.J. Mann 3 ~Clinical Cognitive Neuroscience Laboratory, University of Pittsburgh Medical Center, Pittsburgh, P A 15213; 2Department o f Psychology, Carnegie Mellon University, Pittsburgh, PA; 3New York Psychiatric Institute, N e w York, NY Specific technical problems arise when using blood oxygenationweighted MRI to document activation of limbic structures within individual subjects. In contrast to sensory, motor, or cognitive stimulation procedures, emotional stimulation is typically of progressive onset and offset and difficult to maintain. In addition, limbic structures such as the amygdala and orbital frontal cortex are h~cated near large air cavities that result in signal voids due to spin dephasing in T2-weighted images and commonly produce edge artifacts due to subtle head movements that can easily be misinterpreted as "'activation." We have used a bite-bar procedure and image realignment to minimize edge artifacts, a selection of slice orientation and thickness that minimizes signal wilds, an image reconstruction technique that corrects for distortions due to magnetic field nonuniformity, subtraction of MR angiograms to eliminate spurious activation from blood vessels, a new statistical procedure relying on clustering of pixels to maximize power, and five different emotional activation procedures, including drug challenges with IV yohimbine and IV procaine. We observed large subjective and physiological changes, and statistically significant areas of activation with every procedure. Time--series graphs of MR signal changes suggest a strong correlation with stimulus changes; however, we believe that extreme caution is necessary in interpreting such results because of significant problems with motion artifacts, and unreliability of activation areas across studies in the same subjects and across subjects with the same stimuli. Additional development and testing of activation paradigms and of MR technique appear necessary before fMRI can be used reliably to study activation of limbic structures.
228. EFFECTS OF AMPHETAMINE IN MAJOR DEPRESSIVE DISORDER USING FUNCTIONAL MRI M.H. Trivedi, T. Blackburn, S. Lewis, R. McColl, R. Peshock, A.J. Rush, & B. Grannemann University o f Texas Southwestern Medical Center at Dallas, Dallas, TX 75235 Major depressive disorder (MDD) has clear biological underpinnings. PET and SPECT have provided evidence of abnormal CNS function al-
BIOL PSYCHIATRY 657 1995;37:593-683
though resting state findings are often inconsistent. Amphetamine challenge paradigm combined with in vivo functional brain imaging provides a method to evaluate the function of specific anatomical regions in depression. Both the nigroslriatal and the mesolimbic dopamine pathways have been extensively examined as sites of amphetamine action. Functional MRI (fMRI) uses high-speed, rapid-imaging MR systems to produce "motion pictures" of changes in blood flow perfusion and volume and accomplishes high resolution and characterization of sequential activation of brain regions over time. Deoxyhemoglobin serves as a contrast to measure cerebral blood flow/volume reflecting increased neuronal activity over the study period. The purpose of this research is to map activation of multiple regions throughout the human brain during a pharmacological challenge. Echo Planar fMRI studies were performed using a Picker Vista 1.5T magnet with a single axis bipolar gradient insert using a quadrature head coil. T2* weighted gradient echo image sets (TE 40 msec, 100 x 105 image matrix, FOV 25-30 cm, 66 msec/slice, minimum 20 slices) were obtained over the entire brain over 80 minutes following amphetamine (0.4 mg/kg PO) in six patients with DSM-III-R MDD and six age-matched normals (NC). Three-dimensional functional maps were produced from difference images. Signal intensity changes of 4%-12% were observed in multiple regions of activation during amphetamine challenge, in the substantia nigra, hippocampal/amygdala, and thalamic regions and their prefrontal connections bilaterally. The regions of activation distinguished MDD from NC subjects. (Funded in part by NARSAD (MHT) and MH4 1115 (AJR).)
229. CEREBRAL MRI OF HUMAN BRAIN DEVELOPMENT: AGES 4-18 J.N. Giedd, F.X. Castellanos, J.C. Rajapakse, D. Kaysen, A.C. Vaituzis, Y.C. Vauss, S.D. Hamburger, & J.L. Rapoport Child Psychiatry Branch, NIMH, Bethesda, M D 20892 Cerebral MRI scans of 105 healthy children and adolescents, ages 4-18, were analyzed to assess the effects of age and gender on the sizes of the cerebrum, cerebellum, caudate, globus pallidus, putamen, thalamus, cerebellum, and lateral ventricles in normal development. Significant gender effects were noted for several structures. Males had a 10% larger cerebral and 7% larger cerebellar volume, which remained statistically significant after correction for height and weight (p < 0.001 ). After adjusting for total cerebral volume, putamen and globus pallidus remained larger in males, while caudate volume was larger in females. Cerebral volume as a whole did not change significantly across this age span; however, cerebellar volume increased 18%. In males only, caudate and putamen decreased with age (p = 0.007 and 0.004, respectively). Lateral ventricular volume increased for both genders (p = 0.0007 for males, 0.05 for females), with males showing a significant increase in slope after age 11 (p = 0.03). For cerebral hemispheres and lateral ventricles, there was a significantly greater left than right asymmetry (p = 0.0001 and p = 0.02, respectively). In contrast, caudate and globus pallidus showed a greater right than left asymmetry (p < 0.001 ). The volumes of all structures demonstrated a high degree of natural variability. Females exhibited significantly larger variability than males, after correcting for age, height, and weight effects, for all structures except the globus pallidus (equal variability) and cerebellum (less variability). These findings highlight the need for relatively large gender-matched samples in developmental brain morphometric studies of normal and clinical populations.