Carriers of recessive WNK1/HSN2 mutations for hereditary sensory and autonomic neuropathy type 2 (HSAN2) are more sensitive to thermal stimuli.

Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is a rare recessive genetic disorder characterized by severe sensory loss affecting the tactile, thermal and nociceptive modalities. Although heterozygous carriers of nonsense mutations in the HSN2 gene, called with-no-lysine(K)-1 (WNK1), do not develop the disease, historical and experimental evidence suggests that these individuals might perceive somatosensory stimuli differently from others. Using the method-of-limits, we assessed the thresholds for warmth detection, cool detection, heat pain and cold pain in 25 mutation carriers and 35 controls. In group analyses, carriers displayed significantly lower warmth (p<0.001) and cool (p<0.05) difference thresholds, and also tended to report cold pain at higher temperatures (p=0.095), than controls. Similarly, matched-pair analyses showed that carriers are significantly more sensitive to warm stimuli (p<0.01) and cold pain stimuli (p<0.05), and tend to be more sensitive to cool stimuli (p=0.11). Furthermore, the differences between the warmth detection thresholds of the carriers and those of gender- and sex-matched wild types significantly increased with age (r=0.76, p=0.02), and in carriers cool detection thresholds did not increase with age (r=0.27, p=0.24) as expected and observed in controls (r=0.34, p=0.05). This study demonstrates that the carriers of a recessive mutation for HSAN2 display greater sensitivity to innocuous thermal stimuli, as well as for cold pain, suggesting a possible environmental adaptive advantage of the heterozygous state.

fMRI reveals greater within- than between-hemifield integration in the human lateral occipital cortex.

Early visual areas within each hemisphere (V1, V2, V3/VP, V4v) contain distinct representations of the upper and lower quadrants of the contralateral hemifield. As receptive field size increases, the retinotopy in higher-tier visual areas becomes progressively less distinct. Using functional magnetic resonance imaging (fMRI) to map the visual fields, we found that an intermediate level visual area, the lateral occipital region (LO), contains retinotopic maps with a contralateral bias, but with a combined representation of the upper and lower visual field. Moreover, we used the technique of fMRI adaptation to determine whether neurons in LO code for both the upper and lower contralateral quadrants. We found that even when visual stimulus locations are equivalent across comparisons, the LO was more sensitive to location changes that crossed hemifields than location changes within a hemifield. These results suggested that within high-tier visual areas the increasing integration of visual field information is a two-stage process. The upper and lower visual representations are combined first, in LO, then the left and right representations. Furthermore, these results provided evidence for a neural mechanism to explain behavioral findings of greater integration within than between hemifields.

Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?

Fibromyalgia is an intractable widespread pain disorder that is most frequently diagnosed in women. It has traditionally been classified as either a musculoskeletal disease or a psychological disorder. Accumulating evidence now suggests that fibromyalgia may be associated with CNS dysfunction. In this study, we investigate anatomical changes in the brain associated with fibromyalgia. Using voxel-based morphometric analysis of magnetic resonance brain images, we examined the brains of 10 female fibromyalgia patients and 10 healthy controls. We found that fibromyalgia patients had significantly less total gray matter volume and showed a 3.3 times greater age-associated decrease in gray matter than healthy controls. The longer the individuals had had fibromyalgia, the greater the gray matter loss, with each year of fibromyalgia being equivalent to 9.5 times the loss in normal aging. In addition, fibromyalgia patients demonstrated significantly less gray matter density than healthy controls in several brain regions, including the cingulate, insular and medial frontal cortices, and parahippocampal gyri. The neuroanatomical changes that we see in fibromyalgia patients contribute additional evidence of CNS involvement in fibromyalgia. In particular, fibromyalgia appears to be associated with an acceleration of age-related changes in the very substance of the brain. Moreover, the regions in which we demonstrate objective changes may be functionally linked to core features of the disorder including affective disturbances and chronic widespread pain.

A contralateral preference in the lateral occipital area: sensory and attentional mechanisms.

Here we examined the level of the lateral occipital (LO) area within the processing stream of the ventral visual cortex. An important determinant of an area's level of processing is whether it codes visual elements on both sides of the visual field, as do higher visual areas, or prefers those in the contralateral visual field, as do early visual areas. The former would suggest that LO, on one side, combines bilateral visual elements into a whole, while the latter suggests that it codes only the parts of forms. We showed that LO has a relative preference for visual objects in the contralateral visual field. LO responses were influenced by attention. However, relative changes in LO activity caused by changes in object location were preserved even when attention was shifted away from the objects to moving random dot patterns on the opposite side. Our data offer a new view on LO as an intermediate, but not a high-level, visual area in which neurons are driven by visual input and spatial attention in a multiplicative fashion.