In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.

Two parallel studies using positron emission tomography, one conducted in neurological patients with brain lesions, the other in normal individuals, indicate that the normal process of retrieving words that denote concrete entities depends in part on multiple regions of the left cerebral hemisphere, located outside the classic language areas. Moreover, anatomically separable regions tends to process words for distinct kinds of items.

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When the landmark patient Phineas Gage died in 1861, no autopsy was performed, but his skull was later recovered. The brain lesion that caused the profound personality changes for which his case became famous has been presumed to have involved the left frontal region, but questions have been raised about the involvement of other regions and about the exact placement of the lesion within the vast frontal territory. Measurements from Gage's skull and modern neuroimaging techniques were used to reconstitute the accident and determine the probable location of the lesion. The damage involved both left and right prefrontal cortices in a pattern that, as confirmed by Gage's modern counterparts, causes a defect in rational decision making and the processing of emotion.

Several mutations in the amyloid precursor protein (APP) gene have been found to associate with pathologic deposition of the beta-amyloid peptide (Abeta) in neuritic plaques or in the walls of cerebral vessels. We report a mutation at a novel site in APP in a three-generation Iowa family with autosomal dominant dementia beginning in the sixth or seventh decade of life. The proband and an affected brother had progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. Neuropathological examination of the proband revealed severe cerebral amyloid angiopathy, widespread neurofibrillary tangles, and unusually extensive distribution of Abeta40 in plaques. The affected brothers shared a missense mutation in APP, resulting in substitution of asparagine for aspartic acid at position 694. This site corresponds to residue 23 of Abeta, thus differing from familial Alzheimer's disease mutations, which occur outside the Abeta sequence. Restriction enzyme analysis of DNA from 94 unrelated patients with sporadic cerebral amyloid angiopathy-related hemorrhage found no other instances of this mutation. These results suggest a novel site within Abeta that may promote its deposition and toxicity.

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Abstract& Cognitive models of word production correlate the word frequency effect (i.e., the fact that words which appear with less frequency take longer to produce) with an increased processing cost to activate the whole-word (lexical) phonological representation. We performed functional magnetic resonance imaging (fMRI) while subjects produced overt naming responses to photographs of animals and manipulable objects that had high name agreement but were of varying frequency, with the purpose of identifying neural structures participating specifically in activating whole-word phonological representations, as opposed to activating lexical semantic representations or articulatorymotor routines. Blood oxygen level-dependent responses were analyzed using a parametric approach based on the frequency with which each word produced appears in the language. Parallel analyses were performed for concept familiarity and word length, which provided indices of semantic and articulatory loads. These analyses permitted us to identify regions related to word frequency alone, and therefore, likely to be related specifically to activation of phonological word forms. We hypothesized that the increased processing cost of producing lower-frequency words would correlate with activation of the left posterior inferotemporal (IT) cortex, the left posterior superior temporal gyrus (pSTG), and the left inferior frontal gyrus (IFG). Scan-time response latencies demonstrated the expected word frequency effect. Analysis of the fMRI data revealed that activity in the pSTG was modulated by frequency but not word length or concept familiarity. In contrast, parts of IT and IFG demonstrated conjoint frequency and familiarity effects, and parts of both primary motor regions demonstrated conjoint effects of frequency and word length. The results are consistent with a model of word production in which lexical-semantic and lexical-phonological information are accessed by overlapping neural systems within posterior and anterior language-related cortices, with pSTG specifically involved in accessing lexical phonology. &