FDG-PET findings in patients with galactosaemia.

Despite treatment with a galactose-restricted diet, many galactosaemia patients develop lifelong cognitive impairment, speech abnormalities and a gamut of neurological problems including cognitive impairment and tremors. No study has explored changes in cerebral glucose metabolism in patients with galactosaemia. Five patients with galactosaemia had ages ranging from 20 to 40 years (mean age 28 years) and eight similarly aged controls received brain [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. PET scans were analysed using a previously validated template methodology of regions of interest (ROIs). Count ratios for each anatomical ROI were compared between the galactosaemic patients and the healthy controls. Statistical parametric mapping (SPM) software was also used to further analyse the data. ROI analysis showed that galactosaemic patients had significant bilateral decreases in cerebral glucose metabolism in the superior temporal gyrus, medial occipital lobe, parietal lobe, cerebellum, calcarine cortex, superior frontal cortex, and superior parietal cortex when compared with controls. Significant increases were seen in the cingulate gyrus and temporal poles, bilaterally. SPM analysis revealed foci of decreased glucose metabolism in the caudate, cerebellum, precentral gyrus and cerebellar tonsils of galactosaemic patients. SPM also showed increased glucose metabolism in the subcallosal gyrus and claustrum. The results show significant abnormalities in cerebral function in patients with galactosaemia, particularly with widespread decreases in cortical metabolism. These abnormalities appear to be in brain regions that may be associated with the neuropsychological deficits in these patients. PET brain scans may be of value in galactosaemia patients to evaluate for dysfunction.

Use of Standardized Uptake Value Ratios Decreases Interreader Variability of [18F] Florbetapir PET Brain Scan Interpretation.

BACKGROUND AND PURPOSE: Fluorine-18 florbetapir is a recently developed ß-amyloid plaque positron-emission tomography imaging agent with high sensitivity, specificity, and accuracy in the detection of moderate-to-frequent cerebral cortical ß-amyloid plaque. However, the FDA has expressed concerns about the consistency of interpretation of [(18)F] florbetapir PET brain scans. We hypothesized that incorporating automated cerebral-to-whole-cerebellar standardized uptake value ratios into [(18)F] florbetapir PET brain scan interpretation would reduce this interreader variability. MATERIALS AND METHODS: This randomized, blinded-reader study used previously acquired [(18)F] florbetapir scans from 30 anonymized patients who were enrolled in the Alzheimer's Disease Neuroimaging Initiative 2. In 4 separate, blinded-reading sessions, 5 readers classified 30 cases as positive or negative for significant ß-amyloid deposition either qualitatively alone or qualitatively with additional adjunct software that determined standardized uptake value ratios. A κ coefficient was used to calculate interreader agreement with and without the use of standardized uptake value ratios. RESULTS: There was complete interreader agreement on 20/30 cases of [(18)F] florbetapir PET brain scans by using qualitative interpretation and on 27/30 scans interpreted with the adjunct use of standardized uptake value ratios. The κ coefficient for the studies read with standardized uptake value ratios (0.92) was significantly higher compared with the qualitatively read studies (0.69, P = .006). CONCLUSIONS: Use of standardized uptake value ratios improves interreader agreement in the interpretation of [(18)F] florbetapir images.

Patterns of lateral sensory cortical activation determined using functional magnetic resonance imaging.

OBJECT: Functional magnetic resonance (fMR) imaging was performed in human volunteers to determine the lateral perisylvian cortical areas activated by innocuous cutaneous stimulation. METHODS: Eight volunteers who underwent 53 separate experiments form the basis of this report. Eight contiguous coronal slices were obtained using echoplanar fMR imaging techniques while participants were at rest and while somatosensory activation stimuli consisting of vibration or air puffs were delivered to various body areas. The data were analyzed using Student's t-test and cluster analysis to determine significant differences between the resting and activated states. The findings were as follows: the areas in the lateral cortex activated by the stimuli were the primary sensory cortex (SI), the second somatosensory area (SII), the insula, the superior parietal lobule, and the retroinsular parietal operculum (RIPO). Somatotopy was demonstrable in SI but not in the other areas identified. There was a surprisingly low correlation between the amount of cortex activated in the various areas, which could mean separate inputs and functions for the areas identified. The highest correlation was found between activity in SII and RIPO (0.69). CONCLUSIONS: The authors maintain that fMR imaging can be used to identify multiple lateral somatosensory areas in humans. Somatotopy is demonstrated in SI but not in the other lateral cortical sensory areas. The correlations between the amounts of cortex activated in the different lateral sensory areas are low. Recognition of the multiple lateral sensory areas is important both for understanding sensory cortical function and for safe interpretation of studies designed to identify the central sulcus by activating SI.

Anomalous functional organization of barrel cortex in GAP-43 deficient mice.

Growth associated protein 43 (GAP-43), found only in the nervous system, regulates the response of neurons to axon guidance signals. It is also critical for establishing normal somatotopy. Mice lacking GAP-43 (KO) show aberrant pathfinding by thalamocortical afferents, and do not form cortical whisker/barrels. GAP-43 heterozygous (HZ) mice show more subtle deficits--delayed barrel segregation and enlarged barrels at postnatal day 7. Here, we used cortical intrinsic signal imaging to characterize adult somatotopy in wildtype (WT), GAP-43 KO, and HZ mice. We found clear foci of activation in GAP-43 KO cortex in response to single-whisker stimulation. However, the KO spatial activation patterns showed severe anomalies, indicating a loss of functional somatotopy. In some cases, multiple foci were activated by single whiskers, while in other cases, the same cortical zone was activated by several whiskers. The results are consistent with our previous findings of aberrant pathfinding and clustering by thalamocortical afferent axons, and absence of barrel patterning. Our findings indicate that cortex acts to cluster afferents from a given whisker, even in the absence of normal topography. By contrast, single-whisker stimulation revealed normal adult topographic organization in WT and HZ mice. However, we found that functional representations of adult HZ barrels are larger than those found in WT mice. Since histological HZ barrels recover normal dimensions by postnatal day 26, the altered circuit function in GAP-43 HZ cortex could be a secondary consequence of the rescue of barrel dimensions.

Use-dependent plasticity in barrel cortex: intrinsic signal imaging reveals functional expansion of spared whisker representation into adjacent deprived columns.

We used optical imaging of intrinsic cortical signals, elicited by whisker stimulation, to define areas of activation in primary sensory cortex of normal hamsters and hamsters subjected to neonatal follicle ablation at postnatal day seven (P7). Follicle ablations were unilateral, and spared either C-row whiskers or the second whisker arc. This study was done to determine if the intrinsic cortical connectivity pattern of the barrel cortex, established during the critical period, affects the process of representational plasticity that follows whisker follicle ablation. Additionally, we tested the ability to monitor such changes in individual cortical whisker representations using intrinsic signal imaging. Stimulation of a single whisker yielded peak activation of a barrel-sized patch in the somatotopically appropriate location in normal cortex. In both row and arc-spared animals, functional representations corresponding to spared follicles were significantly stronger and more oblong than normal. The pattern of activation differed in the row-sparing and arc-sparing groups, in that the expansion was preferentially into deprived, not spared areas. Single whisker stimulation in row-spared cases preferentially activated the corresponding barrel arc, while stimulation of one whisker in arc-spared cases produced elongated activation down the barrel row. Since whisker deflection normally has a net inhibitory effect on neighboring barrels, our data suggest that intracortical inhibition fails to develop normally in deprived cortical columns. Because thalamocortical projections are not affected by follicle ablation after P7, we suggest that the effects we observed are largely cortical, not thalamocortical.