A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n=10); from a larger study on prescription opioid dependent patients (n=133)] and matched healthy individuals (n=10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.
During migraine attacks, alterations in sensation accompanying headache may manifest as allodynia and enhanced sensitivity to light, sound, and odors. Our objective was to identify physiological changes in cortical regions in migraine patients using painful heat and functional magnetic resonance imaging (fMRI) and the structural basis for such changes using diffusion tensor imaging (DTI). In 11 interictal patients, painful heat threshold + 1°C was applied unilaterally to the forehead during fMRI scanning. Significantly greater activation was identified in the medial temporal lobe in patients relative to healthy subjects, specifically in the anterior temporal pole (TP). In patients, TP showed significantly increased functional connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In 9 healthy subjects, DTI identified white matter connectivity between TP and pulvinar nucleus, which has been related to migraine. In 8 patients, fMRI activation in TP with painful heat was exacerbated during migraine, suggesting that repeated migraines may sensitize TP. This article investigates a nonclassical role of TP in migraineurs. Observed temporal lobe abnormalities may provide a basis for many of the perceptual changes in migraineurs and may serve as a potential interictal biomarker for drug efficacy.
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