A traditional method of localizing brain functions has been to identify shared areas of brain damage in individuals who have a particular deficit. The rationale of this 'lesion overlap' approach is straightforward: if the individuals can no longer perform the function, the area of brain damaged in most of these individuals must have been responsible for that function. However, the reciprocal association, i.e. the probability of the lesion causing the deficit, is often not evaluated. In this study, we illustrate potential weaknesses of this approach, by re-examining regions of the brain essential for orchestrating speech articulation. A particularly elegant and widely cited lesion overlap study identified the superior part of the precentral gyrus of the insula (in the anterior insula) as the shared area of damage in chronic stroke patients with 'apraxia of speech', a disorder of motor planning and programming of speech. Others have confirmed that patients with apraxia of speech commonly have damage to the anterior insula. However, this reliable association might reflect the vulnerability of the insula to damage following occlusion or narrowing of the middle cerebral artery (which can independently cause apraxia of speech and many other deficits). To evaluate this possibility, we examined the relationship between apraxia of speech and the insula in three unique ways: (i) we determined the probability of the lesion causing the deficit, as well as the deficit being associated with the lesion, by examining speech articulation and advanced MRIs in two consecutive series of patients with acute left hemisphere, non-lacunar stroke, 40 with and 40 without insular damage; (ii) we studied patients at stroke onset to identify the deficit before it resolved in cases of small stroke; and (iii) we identified regions of dysfunctional brain tissue, as well as structural damage. Using this approach, we found no association between apraxia of speech and lesions of the left insula, anterior insula or superior tip of the precentral gyrus of the insula. Instead, in patients with and without insular lesions, apraxia of speech was associated with structural damage or low blood flow in left posterior inferior frontal gyrus. These results illustrate a potential limitation of lesion overlap studies, and illustrate an alternative method for identifying brain-behaviour relationships.

Impaired day-to-day communication in nonaphasic frontotemporal dementia patients with a disorder of social comportment and executive functioning is due in part to a striking deficit in discourse organization associated with right frontotemporal disease. Difficulty with discourse in progressive aphasia is due largely to the language impairments of these patients.

We assessed cerebrospinal fluid (CSF) levels of tau and other biomarkers of neurodegenerative disease. CSF tau levels vary widely in reports of frontotemporal dementia (FTD). CSF samples were assayed for tau, amyloid beta1-42 (A1-42), and the isoprostane 8,12-iso-iPF2a-VI (iP) prospectively in 64 patients with FTD, retrospectively in 26 autopsied cases with FTD or Alzheimer's disease (AD), and in 13 healthy seniors. To validate our observations in vivo, we correlated CSF tau levels with cortical atrophy in 17 FTD patients using voxel-based morphometry analyses of high-resolution magnetic resonance imaging. CSF levels of tau, Abeta1-42, and iP differed significantly in FTD compared with AD. Individual patient analyses showed that 34% of FD patients had significantly low levels of CSF tau, although this was never seen in AD. A discriminant analysis based on CSF levels of tau, Abeta1-42, and iP was able to classify 88.5% of these patients in a manner that corresponds to their clinical or autopsy diagnosis. Magnetic resonance imaging studies showed that CSF tau levels correlate significantly with right frontal and left temporal cortical atrophy, brain regions known to be atrophic in patients with autopsy-proved FTD. We conclude that CSF tau levels are significantly reduced in many patients with FTD.

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