The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10 -20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm 3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

Primary progressive aphasia (PPA) is a neurodegenerative dementia syndrome principally characterized by the gradual dissolution of language functions, especially in the early stages of disorder. In a previous functional neuroimaging study, PPA patients were found to activate core language areas similarly to control subjects when performing semantic and phonological processing tasks (Sonty et al., 2003). In the present study, functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were used to study multiregional effective connectivity in early-stage PPA (n ϭ 8) and control (n ϭ 8) subjects performing semantic word matching and visual letter matching tasks. fMRI analysis showed semantic task-specific activations in the left inferior frontal (Broca's area) and posterior superior temporal (Wernicke's area) regions, in addition to other language regions, in both groups. Using a model language network consisting of six left hemisphere regions, the DCM analysis demonstrated reduced language-specific effective connectivity between Wernicke's and Broca's areas in the PPA patient group. Furthermore, this decrement in connectivity was predictive of semantic task accuracy. These results demonstrate for the first time that dysfunctional network interactions (effective connectivity), rather than hypoactivity within individual brain regions, may contribute to the emergence of language deficits seen in PPA.

Primary Progressive Aphasia (PPA) is a behaviorally focal dementia syndrome with deterioration of language functions but relative preservation of other cognitive domains for at least the first two years of disease. In this study, PPA patients with impaired word finding but intact comprehension of conversational speech and their matched control subjects were examined using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI). fMRI compared signal changes during phonological and semantic language tasks with those during a control task (matching letters). PPA patients showed longer reaction times and reduced accuracy versus controls on the language tasks, but no performance differences on the control task. VBM demonstrated reduced gray matter in left superior temporal and inferior parietal regions in the PPA group. However, these patients showed a normal pattern of activation within the classical language regions. In addition, PPA patients showed activations, not seen in normals, in fusiform gyrus, precentral gyrus, and intra-parietal sulcus. These activations were found to correlate negatively with measures of naming and task performance. The additional activations in PPA may therefore represent a compensatory spread of language-related neural activity or a failure to suppress activity in areas normally inhibited during language tasks.

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