Results: 4

1.
Figure 1

Figure 1. Dichotomous anatomy and physiology of dSPNs and iSPNs.. From: Brain networks in Huntington disease.

(A) Reconstructions of biocytin-filled dSPNs and iSPNs from P35–P45 BAC transgenic mice; a GABAergic interneuron is shown for comparison. (B) Plot of dendritic intersections in dSPNs and iSPNs as a function of distance from the soma that was derived from 3-dimensional reconstructions. (C) Summary of the responses of dSPNs and iSPNs to a range of intrasomatic current steps; iSPNs were more excitable over a broad range of injected currents. Adapted with permission from Journal of Neuroscience (9).

David Eidelberg, et al. J Clin Invest. 2011 February 1;121(2):484-492.
2.
Figure 3

Figure 3. Metabolic activity at key network nodes.. From: Brain networks in Huntington disease.

(A) In the putamen, metabolic activity declined over time in premanifest subjects (P < 0.005). Relatively greater reductions were observed in the subgroup of premanifest gene carriers who subsequently phenoconverted (red) as compared to those who remained asymptomatic (blue). Mean metabolic activity is also displayed for the whole group (black). (B) Regional metabolic activity was also reduced in the cingulate cortex at all 3 time points, without significant longitudinal change. (C) In the thalamus, metabolic activity declined over time (P < 0.01). In the premanifest subjects who did not phenoconvert, thalamic metabolism was elevated at baseline and remained above normal at the subsequent two longitudinal time points. By contrast, baseline thalamic metabolic activity was also elevated in the premanifest subjects who subsequently phenoconverted, but then declined to normal levels as symptoms emerged. (D) Cerebellar metabolism was also elevated at baseline in premanifest subjects, but no subsequent changes were discerned. Mean globally normalized metabolic activity values (± 1 SEM) for the healthy control subjects are represented by horizontal dashed lines. Error bars represent 1 SEM at each time point. Reprinted with permission from Brain (88).

David Eidelberg, et al. J Clin Invest. 2011 February 1;121(2):484-492.
3.
Figure 4

Figure 4. Hypothesized time course of changes in striatal D2 binding, pattern expression, and regional metabolism in premanifest HD. . From: Brain networks in Huntington disease.

The individual growth curve model (114) was applied to the longitudinal imaging data (88) to estimate the time course of these imaging measures in the period prior to clinical diagnosis. The decline in striatal D2 receptor binding (black) begins approximately 25 years before diagnosis (year 0). About 5 years later, striatal metabolism (green) begins to decline. Thalamic metabolic activity (blue) is likely elevated early on (exactly when is not known), but declines to normal levels as clinical signs (Unified HD Rating Scale [UHDRS] score, purple) become evident. HDRP activity is estimated to increase beginning approximately 15 years before diagnosis. This network measure likely increases for a number of years, then declines prior to symptom onset (see text). The horizontal dashed line represents the normal mean. Reprinted with permission from Brain (88).

David Eidelberg, et al. J Clin Invest. 2011 February 1;121(2):484-492.
4.
Figure 2

Figure 2. HDRP.. From: Brain networks in Huntington disease.

(A) This pattern was identified by spatial covariance analysis of 18F-Fluorodeoxyglucose (FDG) PET scans at baseline from 12 premanifest HD gene carriers and 12 age-matched healthy control subjects (115). This pattern is characterized by metabolic decreases in the striatum and cingulate cortex, with relative increases in the ventral thalamus, primary motor cortex (Brodmann areas [BA] 4), and occipital cortex (BA 17, 18). The covariance map was overlaid on T1-weighted magnetic resonance–template images. Voxel weights for the pattern were thresholded at P = 0.005. Voxels with positive region weights (increases) are shown in red, and voxels with negative region weights (decreases) are shown in blue. (B) Time course of HDRP expression in the 12 premanifest gene carriers scanned at baseline and at 18 and 44 months. Mean subject scores are displayed for the 8 premanifest subjects who subsequently phenoconverted (red), the 4 subjects who did not phenoconvert during the period of follow-up (blue), and all 12 subjects (black). Subject scores, reflecting the expression of this pattern, separate the premanifest from the control groups (P < 0.01). (The mean value [± 1 SD] for the healthy control group is represented by dotted lines. Error bars represent 1 SEM at each time point). Reprinted with permission from Brain (88).

David Eidelberg, et al. J Clin Invest. 2011 February 1;121(2):484-492.

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