Receptive amusia: evidence for cross-hemispheric neural networks underlying music processing strategies.

Perceptual musical functions were investigated in patients suffering from unilateral cerebrovascular cortical lesions. Using MIDI (Musical Instrument Digital Interface) technique, a standardized short test battery was established that covers local (analytical) as well as global perceptual mechanisms. These represent the principal cognitive strategies in melodic and temporal musical information processing (local, interval and rhythm; global, contour and metre). Of the participating brain-damaged patients, a total of 69% presented with post-lesional impairments in music perception. Left-hemisphere-damaged patients showed significant deficits in the discrimination of local as well as global structures in both melodic and temporal information processing. Right-hemisphere-damaged patients also revealed an overall impairment of music perception, reaching significance in the temporal conditions. Detailed analysis outlined a hierarchical organization, with an initial right-hemisphere recognition of contour and metre followed by identification of interval and rhythm via left-hemisphere subsystems. Patterns of dissociated and associated melodic and temporal deficits indicate autonomous, yet partially integrated neural subsystems underlying the processing of melodic and temporal stimuli. In conclusion, these data contradict a strong hemispheric specificity for music perception, but indicate cross-hemisphere, fragmented neural substrates underlying local and global musical information processing in the melodic and temporal dimensions. Due to the diverse profiles of neuropsychological deficits revealed in earlier investigations as well as in this study, individual aspects of musicality and musical behaviour very likely contribute to the definite formation of these widely distributed neural networks.

Brain potentials in patients with music perception deficits: evidence for an early locus.

Twelve patients with an acute cerebrovascular accident were assigned to a group with music perception deficits (amusia, n = 6) or a group without such deficits (n = 6) on the basis of a new test-battery for music-perception skills. Event-related brain potentials (ERPs) were recorded in an auditory classification task designed to elicit several components; the N1 as a correlate of initial auditory cortical processing, the P3a as an index of automatic attentional orienting, and the P3b as a measure for controlled stimulus evaluation. Patients with amusia showed a significant amplitude decrement for the P3a relative to controls and patients without amusia suggesting an impairment of early stimulus evaluation. P3b was reduced in both patient groups relative to control. These data show that amusia is quite common in unselected stroke patients and suggest deficits of generic rather than music-specific cognitive processes as the underlying cause.

Assignment of Ptprn2, the gene encoding receptor-type protein tyrosine phosphatase IA-2beta, a major autoantigen in insulin-dependent diabetes mellitus, to mouse chromosome region 12F.

The receptor-type protein tyrosine phosphatase IA-2beta gene (mouse gene symbol Ptprn2) encodes a major autoantigen in insulin-dependent diabetes mellitus. We physically mapped Ptprn2 by fluorescence in situ hybridization to band F of mouse chromosome 12, a region that lacks diabetes susceptibility loci. The mapping confirms the proposed synteny of mouse 12F with band q36 of human chromosome 7.

Assignment of the human gene for receptor-type protein tyrosine phosphatase IA-2 (PTPRN) to chromosome region 2q35 --> q36.1 and identification of an intragenic genetic marker.

Using a mouse protein tyrosine phosphatase cDNA fragment as a probe, cosmid clones containing segments of the human IA-2 PTPase gene (PTPRN) were isolated. The gene was assigned to chromosome region 2q35 --> q36.1 by fluorescence in situ hybridization. In an intronic region of the IA-2 gene a polymorphic microsatellite sequence was found, which will be useful as a genetic marker for the 2q35 --> q36 region.

Molecular cloning of a mouse epithelial protein-tyrosine phosphatase with similarities to submembranous proteins.

Protein-tyrosine phosphatases (PTPases) form an important class of cell regulatory proteins. We have isolated overlapping cDNA clones that together comprise an 8 kb transcript encoding a novel murine PTPase which is expressed in various organs. Sequence analysis revealed an open reading frame of 2,460 amino acid residues. The predicted protein, PTP-BL, is a large non-transmembrane PTPase that exhibits 80% homology with PTP-BAS, a recently described human PTPase. PTP-BL shares some intriguing sequence homologies with submembranous proteins. It contains a band 4.1-like motif also present in the tumor suppressors neurofibromatosis 2 and expanded, five 80 amino acid repeats also present in the discs-large tumor suppressor, and a single catalytic phosphatase domain. No obvious homologies to other proteins were found for the N-terminal region of the protein other than human PTP-BAS. RNA in situ hybridization experiments show that the PTP-BL gene is expressed in epithelial cells, predominantly in kidney, lung, and skin. These data suggest a cell cortical localization for PTP-BL in epithelial cells and a possible role in the morphology and motility of epithelial tissues.

A novel receptor-type protein tyrosine phosphatase with a single catalytic domain is specifically expressed in mouse brain.

Protein tyrosine phosphatases (PTPases) are important regulatory proteins that, together with protein tyrosine kinases, determine the phosphotyrosine levels in cell signalling proteins. By PCR amplification of mouse brain cDNA fragments encoding the catalytic domains of these enzymes, we identified three novel members of the PTPase gene family. Northern-blot analysis showed that two of these novel clones represent brain-specific PTPases, whereas the third originates from a large-sized mRNA that is more ubiquitously expressed. A full-length cDNA encoding one of the brain-specific PTPases, PTP-SL, was isolated. Sequence analysis revealed a transmembrane PTPase containing a single catalytic phosphatase domain that has 45% homology to a rat cytoplasmic brain-specific PTPase named STEP. This suggests a role for PTP-SL in cell-cell signalling processes in the brain.