Neurodegenerative diseases are associated with profound changes in social and emotional function. The emergence of increasingly sophisticated methods for measuring brain volume has facilitated correlation of local changes in tissue content with cognitive and behavioural changes in neurodegenerative disease. The current study examined neuroanatomical correlates of behavioural abnormalities, as measured by the Neuropsychiatric Inventory, in 148 patients with dementia using voxel-based morphometry. Of 12 behaviours examined, 4 correlated with tissue loss: apathy, disinhibition, eating disorders and aberrant motor behaviour. Increasing severity across these four behaviours was associated with tissue loss in the ventral portion of the right anterior cingulate cortex (vACC) and adjacent ventromedial superior frontal gyrus (vmSFG), the right ventromedial prefrontal cortex (VMPC) more posteriorly, the right lateral middle frontal gyrus, the right caudate head, the right orbitofrontal cortex and the right anterior insula. In addition, apathy was independently associated with tissue loss in the right vmSFG, disinhibition with tissue loss in the right subgenual cingulate gyrus in the VMPC, and aberrant motor behaviour with tissue loss in the right dorsal ACC and left premotor cortex. These data strongly support the involvement of the right hemisphere in mediating social and emotional behaviour and highlight the importance of distinct regions on the medial wall of the right frontal lobe in regulating different behaviours. Furthermore, the findings underscore the utility of studying patients with dementia for understanding the neuroanatomical basis of social and emotional functions.

Background: Progressive brain atrophy is associated with the corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP). Regional differences in brain atrophy may reflect the clinical features of disease. Objective: To quantify the structural neuroanatomical differences between CBDS and PSP. Design: A survey of neurologic deficits was conducted in all patients. Voxel-based morphometry was used to quantify structural neuroanatomical differences on magnetic resonance images in each subject group. Setting: University hospital dementia clinic. Participants: Fourteen patients who met clinical research criteria for CBD and 15 patients who met clinical research criteria for PSP, who were matched for severity of disease, age, and functional status, and 80 agematched control subjects. Main Outcome Measures: Statistically significant differences in regional gray and white matter volume, after multiple comparisons correction, between groups of subjects. Results: The patients with CBDS displayed an asymmetric (leftϾright) pattern of brain atrophy that involved the bilateral premotor cortex, superior parietal lobules, and striatum. Progressive supranuclear palsy was associated with atrophy of the midbrain, pons, thalamus, and striatum, with minimal involvement of the frontal cortex. Midbrain structures were more atrophied in PSP than in CBD, whereas dorsal frontal and parietal cortices were more atrophied in CBD than in PSP. The degree of atrophy of the midbrain and pontine tegmentum and the left frontal eye field differentiated the 2 patient groups with 93% accuracy. Conclusions: DistinctpatternsofbrainatrophyexistinCBDS and PSP that can be used to differentiate the 2 diseases. Assessments of brain atrophy in these disorders should be focused on cortical and brainstem ocular motor control areas.

A recent trend in the literature has been to characterize healthcare activities in terms of complex systems theory. Complexity has often been loosely and variously defined, with meanings ranging from "not simple" to "complicated" to "intractable." In this paper, we consider various aspects of complexity and how they relate to modern healthcare practice, with the aim of developing research approaches for studying complex healthcare environments. We propose a theoretical lens for understanding and studying complexity in healthcare systems based on degrees of interrelatedness of system components. We also describe, with relevant caveats, how complex healthcare systems are generally decomposable, rendering them more tractable for further study. The ideas of interrelatedness among the components of a system as a measure of complexity and functional decomposition as a mechanism for studying meaningful subcomponents of a complex system can be used as a framework for understanding complex healthcare systems. Using examples drawn from current literature and our own research, we explain the feasibility of this approach for understanding, studying, and managing complex healthcare systems.

No abstract

Emotional blunting and abnormal processing of rewards and punishments represent early features of frontotemporal lobar degeneration (FTLD). Better understanding of the physiological underpinnings of these emotional changes can be facilitated by the use of classical psychology approaches. Fear conditioning (FC) is an extensively used paradigm for studying emotional processing that has rarely been applied to the study of dementia. We studied FC in controls (n = 25), Alzheimer's disease (n = 25) and FTLD (n = 25). A neutral stimulus (coloured square on a computer screen) was repeatedly paired with a 1 s burst of 100 db white noise. Change in skin conductance response to the neutral stimulus was used to measure conditioning. Physiological-anatomical correlations were examined using voxel-based morphometry (VBM). Both patient groups showed impaired acquisition of conditioned responses. However, the basis for this deficit appeared to differ between groups. In Alzheimer's disease, impaired FC occurred despite normal electrodermal responses to the aversive stimulus. In contrast, FTLD patients showed reduced skin conductance responses to the aversive stimulus, which contributed significantly to their FC deficit. VBM identified correlations with physiological reactivity in the amygdala, anterior cingulate cortex, orbitofrontal cortex and insula. These data indicate that Alzheimer's disease and FTLD both show abnormalities in emotional learning, but they suggest that in FTLD this is associated with a deficit in basic electrodermal response to aversive stimuli, consistent with the emotional blunting described with this disorder. Deficits in responses to aversive stimuli could contribute to both the behavioural and cognitive features of FTLD and Alzheimer's disease. Further study of FC in humans and animal models of dementia could provide a valuable window into these symptoms.