RESUMEN
The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analysis approaches. We investigated a large number of patients with focal unilateral right or left frontal (n = 110) or posterior (n = 100) or subcortical (n = 65) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcel-based lesion-symptom mapping, tract-wise statistical analysis as well as Bayesian multi-variate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcel-based lesion-symptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multi-variate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localized left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of 'energization', which sustains activation for the duration of the task and middle and inferior frontal regions concerned with 'selection', required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes.
RESUMEN
Thrombotic thrombocytopenic purpura (TTP) is a rare thrombomicroangiopathy caused by deficiency of ADAMTS13. Acute neurological involvement is well described, but its long-term impact requires evaluation. One-hundred thirty-one patients, following an acute TTP event, with severe headache or neurological symptoms had a cerebral MRI. Fifty-six percent had abnormal imaging, more commonly in patients with neurological symptoms than headaches only (80% vs. 18%, P < 0·0001). In remission, 27% (n = 35) reported persistent cognitive symptoms: specifically, impaired memory (66%), difficulty concentrating (26%), and word-finding difficulties not secondary to an acute stroke (26%). Sixty-five percent also reported depression and 55% reported anxiety, regardless of presenting neurology. The frontal lobe was disproportionally affected in patients with marked intellectual impairment, seen in 67% of patients compared to 19% of patients without intellectual impairment (P = 0·002). The primary MRI finding in these patients was hyperintense white matter lesions. An abnormal MRI was associated with a lower median verbal IQ (85 vs. 99, P = 0·02) and performance IQ (83 vs. 100, P = 0·02). In conclusion, neurological symptoms are frequently associated with an abnormal cerebral MRI scan, and white matter frontal lobe lesions are particularly significant, leading to marked intellectual impairment. Anxiety and depression were evident in over half of patients, regardless of neurological involvement at presentation.
