Parcellation of functional subdivisions of cingulate cortex and their agreements with distributions of multiple receptor systems

NRM2010 abstracts — Poster presentations

S194

Poster Presentation No.: P117

Methodology

Parcellation of functional subdivisions of cingulate cortex and their agreements with distributions of multiple receptor systems Hiroto Kuwabara, Jongho Kim, Blanca Bisuna, James Brasic, Elise Weerts, Mary McCaul, Gary Wand, Dean Wong Johns Hopkins Medical Institute, USA Objectives: Cingulate cortex may be classified into functional subdivisions based on findings from functional brain mapping studies. Thus, the first aim is to establish and implement a method to identify and subdivide cingulate cortex. Then, we examine whether distributions of binding potential (BPND) within cingulate cortex agree with proposed functional subdivisions using historical PET studies of 7 receptor systems. Materials and Methods: Cingulate VOIs were defined on 24 healthy subjects without neuro-psychiatric disorders and current history of drug addiction who underwent PET scans with [11C]carfentanil, a mu-opioid receptor ligand. Images of BPND were constructed using reference tissue graphical analysis (RTGA; Logan et al., 1996). Parcellation of cingulate VOIs were done as follows: first, bordering sulci (e.g., cingulate, paracingulate, and superior rostral sulci, and inter-hemispheric fissure) were identified on sagittal images by semi-automatic sulci (low MRI density) detection module with minimal updating of seeding points between slices. Then, so-defined sulci VOIs were used to separate gray matter voxels identified by an interactive-segmentation using low/high thresholds from surrounding structures. Altogether, cingulate VOIs were defined without manually tracing the structure. Cingulate VOIs were transferred to a standard space using spatial normalization technique and divided into anterior (aC), middle (mC), and posterior (pC) divisions using commissural planes (Vogt et al., 2003). Anterior cingulate was divided into ventral, rostral, and dorsal divisions using anterior tip of corpus callosum as a landmark (Bush 2000). Then, we examined whether receptor BPND distributions along the long axis of cingulate cortex agree with proposed functional subdivisions using BP maps of the following receptor systems which were obtained on healthy subjects (age: 20–40 years): 5HT 2A ([11C]MDL100,907; n = 12) and 5HT 6 ([11C]GSK-215083; n = 7), mu-opioid ([11C]carfentanil; n = 24), histamine H1 ([11C]doxepine; n = 18) and H3 ([11C]GSK-189254; n = 7), cannabinoid CB1 ([11C]OMAR; n = 10), and peripheral benzodiazepine (PBZ; [11C]flumazenil; n = 12) receptor systems. Results: High BPND areas seen on [11C]CFN BPND maps in medial sagittal slices agreed with individually defined cingulate VOIs on all subjects. BPND values (normalized to cingulate means) in 12 small segments along the long axis are shown in the figure (v: ventral aC; r1–3: rostral aC; d1–3: dorsal aC; m1–3: mC; and p1–2: pC) for the 7 receptor systems. MOR, 5HT2A, 5HT6, and H3 supported subdivisions of aC. The 4 receptor systems and H1 supported subdivisions of mC and pC. However, the data suggested that the posterior one third of mC may be combined with pC. Conclusions: This study indicated the feasibility of functional subdivisions of cingulate cortex based on findings of human brain mapping studies. Comparison to distributions of BPND of 7 receptor systems along the long axis justified proposed subdivisions from PET prospective, except for a possibility that the posterior one third of middle cingulate may be classified as a part of posterior cingulate cortex.

doi:10.1016/j.neuroimage.2010.04.158