A cultural effect on brain function

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.     

Synthesis of fucosyl-containing glycoproteins of the vitelline coat in oocytes of Ciona intestinalis (Ascidia).

The sperm receptors of the ascidian oocyte are located at the outer surface of the vitelline coat (formerly called the chorion). The fucose residues are the receptor's most important components for sperm recognition and binding. We asked whether the fucosyl-containing glycoproteins of the vitelline coat are a product of the oocyte, the follicle cells, or the test cells. Ovaries of Ciona intestinalis were injected with L-[3H]fucose and the progress of its incorporation was followed by using autoradiography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the injected gonads and of the isolated vitelline coats. We found that incorporation of fucose begins within the vitellogenic oocytes, and fucose slowly accumulates in the differentiating vitelline coat. At no time could fucose incorporation be detected in the follicle cells or in the test cells. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of vitelline coats prepared from the injected ovaries showed fucose incorporation into the same three glycoproteins present in vitelline coats from mature oocytes and identified by their affinity for 125I-labeled fucose-binding protein [Pinto, M. R., De Santis, R., D'Alessio, G. & Rosati, F. (1981) Exp. Cell Res. 132, 289-295]. A radioactive band not found in the mature oocyte was also present.     

VOWELS IN THE BUFFER: A CASE STUDY OF ACQUIRED DYSGRAPHIA WITH SELECTIVE VOWEL SUBSTITUTIONS

We report the case of a patient who recovered from a clinical picture of fluent aphasia to selective dysgraphia. The features of the writing disorder were compatible with a graphemic output buffer dysfunction (errors in all spelling tasks and for all type of material, affected by word length and consisting mostly of graphemic deviations), with the exception of the lack of transposition errors and position preference. Further, the spelling disorder was selective for vowels, replicating the original observation by Cubelli (1991). A similar, although milder, error pattern was also observed in reading tasks, in particular for nonwords, suggesting that the locus of dysfunction involves a processing stage shared by reading and writing. These findings support the notion that the consonant-vowel status is a property of graphemic representations, and is compatible with that a common buffer is involved in spelling and reading. We discuss the implications of selective vowel disorders for current models of the spelling system.     

Human brain networks: a graph theoretical analysis of cortical connectivity normative database from EEG data in healthy elderly subjects

GeroScience - Moving from the hypothesis that aging processes modulate brain connectivity networks, 170 healthy elderly volunteers were submitted to EEG recordings in order to define age-related...     

Impaired long‐term potentiation–like cortical plasticity in presymptomatic genetic frontotemporal dementia

Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long‐term potentiation–like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short‐interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal‐dominant FTD. Ann Neurol 2016;80:472–476     

Markers of Alzheimer's disease in a population attending a memory clinic

BackgroundNew marker-based criteria for the diagnosis of Alzheimer's disease (AD) were recently proposed. We describe their operational translation in 144 consecutive patients referred to our Memory Clinic.MethodsVisual ratings of hippocampal atrophy and of cortical glucose hypometabolism in magnetic resonance imaging and positron emission tomography, and concentrations of total tau and Aβ1-42 in cerebrospinal fluid were assessed in 12 patients with subjective memory complaints (SMCs) (Mini-Mental State Examination [MMSE] score, 28.0 ± 1.1 [mean ± SD]), 37 with mild cognitive impairment (MCI) (MMSE, 25.1 ± 3.6), 55 with AD (MMSE, 21.1 ± 3.5), and 40 with non-AD dementia (MMSE, 21.6 ± 5.5).ResultsThe sensitivity for AD of each individual biomarker was higher (65% to 87%) than for MCI (18% to 50%). Each biomarker's specificity for SMC and non-AD dementias was good to moderate (83% and 53%). Positivity for at least one marker increased the probability 38 times of belonging to the AD group (P < 0.0001).ConclusionThe new diagnostic criteria can be operationalized in clinical routines, but longitudinal studies of MCI patients will need to assess the criteria's prognostic value.     

Proximal myotonic myopathy: a syndrome with a favourable prognosis?

Cardiac involvement in myotonic dystrophy type 1 (DM1) is well known. In contrast, the severity and frequency of cardiac abnormalities in proximal myotonic myopathy (PROMM) are still unclear. To identify similarities and differences in the rate of progression of muscle weakness and cardiac disturbances in these two disorders, 16 patients with PROMM (3q-unlinked PROMM: n=10; uniformative for linkage: n=6) were compared to 33 patients with moderately severe myotonic dystrophy type 1 (DM1). There was no significant difference in disease duration between PROMM and DM1. Patients underwent serial manual muscle strength testing, EKG, 24-h Holter monitoring, 2D-echocardiography. Muscle weakness progressed slowly in both groups. Most DM1 patients developed conduction defects. No significant atrioventricular disturbances on initial and follow-up examinations were found in PROMM patients. One patient developed right bundle branch block. Many families with PROMM appear to have more benign cardiac manifestations and less severe prognosis compared to DM1. Further studies of subgroups of PROMM (linked to the 3q21 locus and without linkage) are necessary to determine whether the cardiac conduction disturbances are more common in a specific genotype of PROMM.     

An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin

The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development.