RESUMEN
The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. 'Splitting' views propose separate clinical entities: 'primary progressive apraxia of speech' when AoS occurs in the absence of expressive agrammatism, 'progressive agrammatic aphasia' (PAA) in the opposite case, and 'AOS + PAA' when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, anatomical and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behaviour to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism or receptive agrammatism. Our cross-sectional examination of brain-behaviour relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioural dissociation/association in previous reports. Second, we identified a 'left-right' and 'ventral-dorsal' neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions; and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicentres within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.
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Afasia Progresiva Primaria , Apraxias , Afasia Progresiva Primaria no Fluente , Humanos , Afasia de Broca/patología , Estudios Prospectivos , Disartria , Habla , Estudios Transversales , Apraxias/patología , Afasia Progresiva Primaria/patología , Afasia Progresiva Primaria no Fluente/complicacionesRESUMEN
Functional imaging studies of neurotypical adults report activation in the left putamen during speech production. The current study asked how stroke survivors with left putamen damage are able to produce correct spoken responses during a range of speech production tasks. Using functional magnetic resonance imaging, activation during correct speech production responses was assessed in 5 stroke patients with circumscribed left dorsal striatal lesions, 66 stroke patient controls who did not have focal left dorsal striatal lesions, and 54 neurotypical adults. As a group, patients with left dorsal striatal damage (our patients of interest) showed higher activation than neurotypical controls in the left superior parietal cortex during successful speech production. This effect was not specific to patients with left dorsal striatal lesions as we observed enhanced activation in the same region in some patient controls and also in more error-prone neurotypical participants. Our results strongly suggest that enhanced left superior parietal activation supports speech production in diverse challenging circumstances, including those caused by stroke damage. They add to a growing body of literature indicating how upregulation within undamaged parts of the neural systems already recruited by neurotypical adults contributes to recovery after stroke.
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Habla , Accidente Cerebrovascular , Adulto , Humanos , Habla/fisiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/patología , Imagen por Resonancia Magnética , Lóbulo Parietal , PutamenRESUMEN
The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through predetermined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface-based approach paired with an anatomically fine-grained parcellation of the cortical surface (i.e., HCP-MMP1.0 atlas). Second, we combined cross-sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter-seeded resting-state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically-intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporoparietal junction regions, predominantly follows at least two partially nonoverlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis.
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Enfermedad de Alzheimer , Afasia Progresiva Primaria , Humanos , Afasia Progresiva Primaria/diagnóstico por imagen , Estudios Transversales , Pruebas Neuropsicológicas , Encéfalo , Atrofia/patología , Enfermedad de Alzheimer/patologíaRESUMEN
BACKGROUND AND AIMS: Ductular reaction (DR) expands in chronic liver diseases and correlates with disease severity. Besides its potential role in liver regeneration, DR plays a role in the wound-healing response of the liver, promoting periductular fibrosis and inflammatory cell recruitment. However, there is no information regarding its role in intrahepatic angiogenesis. In the current study we investigated the potential contribution of DR cells to hepatic vascular remodeling during chronic liver disease. APPROACH AND RESULTS: In mouse models of liver injury, DR cells express genes involved in angiogenesis. Among angiogenesis-related genes, the expression of Slit2 and its receptor Roundabout 1 (Robo1) was localized in DR cells and neoangiogenic vessels, respectively. The angiogenic role of the Slit2-Robo1 pathway in chronic liver disease was confirmed in ROBO1/2-/+ mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine, which displayed reduced intrahepatic neovascular density compared to wild-type mice. However, ROBO1/2 deficiency did not affect angiogenesis in partial hepatectomy. In patients with advanced alcohol-associated disease, angiogenesis was associated with DR, and up-regulation of SLIT2-ROBO1 correlated with DR and disease severity. In vitro, human liver-derived organoids produced SLIT2 and induced tube formation of endothelial cells. CONCLUSIONS: Overall, our data indicate that DR expansion promotes angiogenesis through the Slit2-Robo1 pathway and recognize DR cells as key players in the liver wound-healing response.
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Péptidos y Proteínas de Señalización Intercelular/genética , Hepatopatías Alcohólicas/fisiopatología , Hígado/fisiopatología , Neovascularización Patológica/genética , Proteínas del Tejido Nervioso/genética , Receptores Inmunológicos/genética , Animales , Vasos Sanguíneos/metabolismo , Enfermedad Crónica , Progresión de la Enfermedad , Expresión Génica , Ontología de Genes , Hepatitis Alcohólica/patología , Hepatitis Alcohólica/fisiopatología , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Hígado/metabolismo , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , Ratones , Neovascularización Patológica/patología , Neovascularización Fisiológica/genética , Proteínas del Tejido Nervioso/metabolismo , Organoides , Gravedad del Paciente , Receptores Inmunológicos/metabolismo , Transducción de Señal/genética , Células Madre , Regulación hacia Arriba , Remodelación Vascular , Cicatrización de Heridas , Proteínas RoundaboutRESUMEN
The present study aimed to evaluate the cross-cultural measurement invariance of the Pandemic Grief Scale (PGS) in ten Latin American countries. A total of 2,321 people who had lost a family member or other loved one due to COVID-19 participated, with a mean age of 34.22 years old (SD = 11.99). In addition to the PGS, a single item of suicidal ideation was applied. The unidimensional model of the PGS had adequate fit in most countries and good reliability estimates. There was evidence of measurement invariance by country and gender. Also, a one-point increase in the PGS was associated with an almost twofold increase in the odds of suicidal ideation. Scores greater than or equal to 4 on the PGS are proposed as a cut off to identify individuals with suicidal ideation. Strong evidence of the cross-cultural validity of the PGS is provided.
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Aflicción , COVID-19 , Humanos , Adulto , Ideación Suicida , Reproducibilidad de los Resultados , América Latina , Pandemias , PesarRESUMEN
Broca's area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca's area damage is best explained by the combination of damage to Broca's area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca's two historic cases. Here, we dissociate the effect of damage to Broca's area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca's area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca's area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca's area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca's area than after damage to Broca's area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca's area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca's area; and (iii) the prior association between persistent speech production impairments and Broca's area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus.
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Afasia de Broca/patología , Área de Broca/patología , Lóbulo Frontal/patología , Accidente Cerebrovascular/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/complicacionesRESUMEN
Establishing whether speech and language therapy after stroke has beneficial effects on speaking ability is challenging because of the need to control for multiple non-therapy factors known to influence recovery. We investigated how speaking ability at three time points post-stroke differed in patients who received varying amounts of clinical therapy in the first month post-stroke. In contrast to prior studies, we factored out variance from: initial severity of speaking impairment, amount of later therapy, and left and right hemisphere lesion size and site. We found that speaking ability at one month post-stroke was significantly better in patients who received early therapy (n = 79), versus those who did not (n = 64), and the number of hours of early therapy was positively related to recovery at one year post-stroke. We offer two non-mutually exclusive interpretations of these data: (1) patients may benefit from the early provision of self-management strategies; (2) therapy is more likely to be provided to patients who have a better chance of recovery (e.g., poor physical and/or mental health may impact suitability for therapy and chance of recovery). Both interpretations have implications for future studies aiming to predict individual patients' speech outcomes after stroke, and their response to therapy.
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Afasia , Accidente Cerebrovascular , Humanos , Afasia/etiología , Terapia del Lenguaje , Habla , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Logopedia , SobrevivientesRESUMEN
The aim of the study was to analyze the psychometric properties of the Spanish version of the Coronavirus Anxiety Scale (CAS), using Item Response Theory (IRT) and Confirmatory Factor Analysis (CFA). The participants were 790 Peruvians, selected through a convenience sampling, where the majority were women. The CFA models indicated that the one-dimensional structure better represents the data, is reliable and invariant between men and women. Likewise, IRT findings indicate that CAS is more informative for high levels of COVID-19 anxiety. The CAS in Spanish has adequate psychometric properties to be used as a short measure of COVID-19 anxiety.
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COVID-19 , Ansiedad/diagnóstico , Análisis Factorial , Femenino , Humanos , Masculino , Perú , Psicometría/métodos , Reproducibilidad de los ResultadosRESUMEN
The Coronavirus Anxiety Scale (CAS) was recently developed to assess dysfunctional anxiety related to COVID-19. Although different studies reported that the CAS is psychometrically sound, it is unclear whether it is invariant across countries. Therefore, the present study aimed to examine the measurement invariance of the CAS in twelve Latin American countries (Argentina, Bolivia, Chile, Colombia, Cuba, Ecuador, El Salvador, Guatemala, Mexico, Paraguay, Peru, and Uruguay). A total of 5196 people participated, with a mean age of 34.06 (SD = 26.54). Multigroup confirmatory factor analysis (CFA) was used to examine the measurement invariance of the CAS across countries and gender. Additionally, the graded response model (GRM) was used to provide a global representation of the representativeness of the scale with respect to the COVID-19 dysfunctional anxiety construct. The unidimensional structure of the five-item CAS was not confirmed in all countries. Therefore, it was suggested that a four-item model of the CAS (CAS-4) provides a better fit across the twelve countries and reliable scores. Multigroup CFA showed that the CAS-4 exhibits scalar invariance across all twelve countries and all genders. In addition, the CAS-4 items are more informative at average and high levels of COVID-19 dysfunctional anxiety than at lower levels. According to the results, the CAS-4 is an instrument with strong cross-cultural validity and is suitable for cross-cultural comparisons of COVID-19 dysfunctional anxiety symptoms in the general population of the twelve Latin American countries evaluated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-021-02563-0.
RESUMEN
The aim of this study was to evaluate the psychometric evidence of the original and short versions of the Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ) in Spanish in a sample of 245 Peruvian adolescents and adults (mean age = 21.04 years, SD = 3.07, 47.8% male and 52.2% female), selected by nonprobabilistic convenience sampling. Additionally, the Coronavirus Anxiety Scale and the Satisfaction with Life Scale were applied. Confirmatory Factor Analysis, internal consistency reliability methods, hierarchical sequence of variance models, and a graded response model were used. Results indicate that both versions of the SCSRFQ showed robust psychometric properties: adequate unidimensional structure, adequate difficulty and discrimination parameters, and significant relationships with the measures of fear of COVID-19 and satisfaction with life. The original version of the SCSRFQ showed evidence of strict measurement invariance by sex and age, whereas the short version showed strict invariance by sex and configural invariance by age. Both versions showed acceptable reliability indices. In conclusion, the original and short versions of the SCSRFQ in Spanish show evidence of psychometric indicators that support their use to assess the strength of religious faith.
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Controversy surrounds the interpretation of higher activation for pseudoword compared to word reading in the left precentral gyrus and pars opercularis. Specifically, does activation in these regions reflect: (1) the demands on sublexical assembly of articulatory codes, or (2) retrieval effort because the combinations of articulatory codes are unfamiliar? Using fMRI, in 84 neurologically intact participants, we addressed this issue by comparing reading and repetition of words (W) and pseudowords (P) to naming objects (O) from pictures or sounds. As objects do not provide sublexical articulatory cues, we hypothesis that retrieval effort will be greater for object naming than word repetition/reading (which benefits from both lexical and sublexical cues); while the demands on sublexical assembly will be higher for pseudoword production than object naming. We found that activation was: (i) highest for pseudoword reading [P>O&W in the visual modality] in the anterior part of the ventral precentral gyrus bordering the precentral sulcus (vPCg/vPCs), consistent with the sublexical assembly of articulatory codes; but (ii) as high for object naming as pseudoword production [P&O>W] in dorsal precentral gyrus (dPCg) and the left inferior frontal junction (IFJ), consistent with retrieval demands and cognitive control. In addition, we dissociate the response properties of vPCg/vPCs, dPCg and IFJ from other left frontal lobe regions that are activated during single word speech production. Specifically, in both auditory and visual modalities: a central part of vPCg (head and face area) was more activated for verbal than nonverbal stimuli [P&W>O]; and the pars orbitalis and inferior frontal sulcus were most activated during object naming [O>W&P]. Our findings help to resolve a previous discrepancy in the literature, dissociate three functionally distinct parts of the precentral gyrus, and refine our knowledge of the functional anatomy of speech production in the left frontal lobe.
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Mapeo Encefálico/métodos , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiología , Imagen por Resonancia Magnética , Reconocimiento Visual de Modelos/fisiología , Medición de la Producción del Habla , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , LecturaRESUMEN
Prior studies have shown that the left posterior superior temporal sulcus (pSTS) and left temporo-parietal junction (TPJ) both contribute to phonological short-term memory, speech perception and speech production. Here, by conducting a within-subjects multi-factorial fMRI study, we dissociate the response profiles of these regions and a third region - the anterior ascending terminal branch of the left superior temporal sulcus (atSTS), which lies dorsal to pSTS and ventral to TPJ. First, we show that each region was more activated by (i) 1-back matching on visually presented verbal stimuli (words or pseudowords) compared to 1-back matching on visually presented non-verbal stimuli (pictures of objects or non-objects), and (ii) overt speech production than 1-back matching, across 8 types of stimuli (visually presented words, pseudowords, objects and non-objects and aurally presented words, pseudowords, object sounds and meaningless hums). The response properties of the three regions dissociated within the auditory modality. In left TPJ, activation was higher for auditory stimuli that were non-verbal (sounds of objects or meaningless hums) compared to verbal (words and pseudowords), irrespective of task (speech production or 1-back matching). In left pSTS, activation was higher for non-semantic stimuli (pseudowords and hums) than semantic stimuli (words and object sounds) on the dorsal pSTS surface (dpSTS), irrespective of task. In left atSTS, activation was not sensitive to either semantic or verbal content. The contrasting response properties of left TPJ, dpSTS and atSTS was cross-validated in an independent sample of 59 participants, using region-by-condition interactions. We also show that each region participates in non-overlapping networks of frontal, parietal and cerebellar regions. Our results challenge previous claims about functional specialisation in the left posterior superior temporal lobe and motivate future studies to determine the timing and directionality of information flow in the brain networks involved in speech perception and production.
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Mapeo Encefálico , Cerebelo/fisiología , Corteza Cerebral/fisiología , Red Nerviosa/fisiología , Psicolingüística , Percepción del Habla/fisiología , Habla/fisiología , Lóbulo Temporal/fisiología , Adulto , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Lectura , Lóbulo Temporal/diagnóstico por imagen , Adulto JovenRESUMEN
It has been demonstrated that the ceramic pot filters (CPFs) with impregnated colloidal silver are efficient for the removal of turbidity and pathogens for household water treatment. This investigation evaluated the efficiency of two filter models for the removal of chemical contaminants (Hg, Pb, As and phenolic compounds) during 175 days. The first model is a traditional CPF impregnated with colloidal silver and the second consists of the ceramic silver-impregnated pot plus a post-filtration column with granular activated carbon and zeolite (CPF + GAC-Z). The results of the CPF showed average efficiencies of 91.5% (Hg), 92% (Pb), 50.2% (As) and 78.7% (phenols). The CPF + GAC-Z showed similar efficiencies for the removal of heavy metals (92.5% Hg, 98.1% Pb and 52.3% As) and a considerably higher efficiency for the removal of phenols (96.4%). The As concentration of the filtered water in both systems was higher than the regulatory limit. The ceramic pot was responsible for the highest removal of chemical compounds. It can be concluded that the traditional CPF is a viable option for water supply treatment at the household level for the removal of chemical contaminants. The efficiency of this filter can be improved with the post-filtration column mainly for the removal of organic constituents.
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Metales Pesados , Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Cerámica , Filtración , FenolesRESUMEN
Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional MRI data from neurologically normal participants, we investigated when and why right hemisphere strokes cause language disorders. Experiment 1 studied right-handed patients with unilateral strokes that damaged the right (n = 109) or left (n = 369) hemispheres. The most frequently impaired language task was: auditory sentence-to-picture matching after right hemisphere strokes; and spoken picture description after left hemisphere strokes. For those with auditory sentence-to-picture matching impairments after right hemisphere strokes, the majority (n = 9) had normal performance on tests of perceptual (visual or auditory) and linguistic (semantic, phonological or syntactic) processing. Experiment 2 found that these nine patients had significantly more damage to dorsal parts of the superior longitudinal fasciculus and the right inferior frontal sulcus compared to 75 other patients who also had right hemisphere strokes but were not impaired on the auditory sentence-to-picture matching task. Damage to these right hemisphere regions caused long-term speech comprehension difficulties in 67% of patients. Experiments 3 and 4 used functional MRI in two groups of 25 neurologically normal individuals to show that within the regions identified by Experiment 2, the right inferior frontal sulcus was normally activated by (i) auditory sentence-to-picture matching; and (ii) one-back matching when the demands on linguistic and non-linguistic working memory were high. Together, these experiments demonstrate that the right inferior frontal cortex contributes to linguistic and non-linguistic working memory capacity (executive function) that is needed for normal speech comprehension. Our results link previously unrelated literatures on the role of the right inferior frontal cortex in executive processing and the role of executive processing in sentence comprehension; which in turn helps to explain why right inferior frontal activity has previously been reported to increase during recovery of language function after left hemisphere stroke. The clinical relevance of our findings is that the detrimental effect of right hemisphere strokes on language is (i) much greater than expected; (ii) frequently observed after damage to the right inferior frontal sulcus; (iii) task dependent; (iv) different to the type of impairments observed after left hemisphere strokes; and (v) can result in long-lasting deficits that are (vi) not the consequence of atypical language lateralization.
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Comprensión , Lóbulo Frontal/patología , Trastornos del Lenguaje/patología , Trastornos del Lenguaje/psicología , Percepción del Habla , Accidente Cerebrovascular/complicaciones , Femenino , Lateralidad Funcional , Humanos , Trastornos del Lenguaje/etiología , Lingüística , Masculino , Memoria a Corto Plazo , Persona de Mediana EdadRESUMEN
Transcranial magnetic stimulation focused on either the left anterior supramarginal gyrus or opercular part of the left inferior frontal gyrus has been reported to transiently impair the ability to perform phonological more than semantic tasks. Here we tested whether phonological processing abilities were also impaired following lesions to these regions in right-handed, English speaking adults, who were investigated at least 1 year after a left-hemisphere stroke. When our regions of interest were limited to 0.5 cm3 of grey matter centred around sites that had been identified with transcranial magnetic stimulation-based functional localization, phonological impairments were observed in 74% (40/54) of patients with damage to the regions and 21% (21/100) of patients sparing these regions. This classification accuracy was better than that observed when using regions of interest centred on activation sites in previous functional magnetic resonance imaging studies of phonological processing, or transcranial magnetic stimulation sites that did not use functional localization. New regions of interest were generated by redefining the borders of each of the transcranial magnetic stimulation sites to include areas that were consistently damaged in the patients with phonological impairments. This increased the incidence of phonological impairments in the presence of damage to 85% (46/54) and also reduced the incidence of phonological impairments in the absence of damage to 15% (15/100). The difference in phonological processing abilities between those with and without damage to these 'transcranial magnetic stimulation-guided' regions remained highly significant even after controlling for the effect of lesion size. The classification accuracy of the transcranial magnetic stimulation-guided regions was validated in a second sample of 108 patients and found to be better than that for (i) functional magnetic resonance imaging-guided regions; (ii) a region identified from an unguided lesion overlap map; and (iii) a region identified from voxel-based lesion-symptom mapping. Finally, consistent with prior findings from functional imaging and transcranial magnetic stimulation in healthy participants, we show how damage to our transcranial magnetic stimulation-guided regions affected performance on phonologically more than semantically demanding tasks. The observation that phonological processing abilities were impaired years after the stroke, suggests that other brain regions were not able to fully compensate for the contribution that the transcranial magnetic stimulation-guided regions make to language tasks. More generally, our novel transcranial magnetic stimulation-guided lesion-deficit mapping approach shows how non-invasive stimulation of the healthy brain can be used to guide the identification of regions where brain damage is likely to cause persistent behavioural effects.
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Mapeo Encefálico/métodos , Trastornos del Lenguaje/fisiopatología , Imagen por Resonancia Magnética/métodos , Evaluación de Resultado en la Atención de Salud , Accidente Cerebrovascular/fisiopatología , Estimulación Magnética Transcraneal/métodos , Adulto , Anciano , Anciano de 80 o más Años , Afasia/diagnóstico por imagen , Afasia/etiología , Afasia/fisiopatología , Femenino , Estudios de Seguimiento , Voluntarios Sanos , Humanos , Trastornos del Lenguaje/diagnóstico por imagen , Trastornos del Lenguaje/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Semántica , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Adulto JovenRESUMEN
Niemann-Pick C disease is a neurovisceral disorder caused by mutations in the NPC gene that result in systemic accumulation of intracellular cholesterol. Although neurodegeneration defines the disease's severity, in most patients it is preceded by hepatic complications such as cholestatic jaundice or hepatomegaly. To analyze the contribution of the hepatic disease in Niemann-Pick C disease progression and to evaluate the degree of primary and secondary hepatic damage, we generated a transgenic mouse with liver-selective expression of NPC1 from embryonic stages. Hepatic NPC1 re-expression did not ameliorate the onset and progression of neurodegeneration of the NPC1-null animal. However, the mice showed reduced hepatomegalia and dramatic, although not complete, reduction of hepatic cholesterol and serum bile salts, bilirubin, and transaminase levels. Therefore, hepatic primary and secondary cholesterol deposition and damage occur simultaneously during Niemann-Pick C disease progression.
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Colesterol/metabolismo , Modelos Animales de Enfermedad , Hepatopatías/complicaciones , Hígado/metabolismo , Enfermedad de Niemann-Pick Tipo C/metabolismo , Proteínas/genética , Animales , Ácidos y Sales Biliares/sangre , Bilirrubina/sangre , Colesterol/análisis , Progresión de la Enfermedad , Células Madre Embrionarias , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Hígado/patología , Hepatopatías/genética , Hepatopatías/metabolismo , Hepatopatías/patología , Masculino , Ratones , Ratones Noqueados , Proteína Niemann-Pick C1 , Enfermedad de Niemann-Pick Tipo C/complicaciones , Enfermedad de Niemann-Pick Tipo C/genética , Enfermedad de Niemann-Pick Tipo C/patología , Proteínas/metabolismo , Transaminasas/sangreRESUMEN
INTRODUCTION: Physical activity acts as an adjuvant in the treatment of numerous diseases and in the promotion of healthy aging. Increasing longevity entails an increase in the demand for professionals who prescribe physical activity, specifically physiotherapists and physical-activity educators. OBJECTIVES: The main objective of this study was to explore the perceptions of a group of third- and fourth-year Physiotherapy students (n=9) and Sport Sciences students (n=5), and experts who work with older adults (n=3) about their knowledge of the older adult population and healthy aging. The secondary objectives were to: (a) explore what knowledge future professionals need about physical activity programming and about physical activity programs aimed at maintaining and improving health among older adults; (b) explore what would be the best methodology to acquire such knowledge; and (c) explore whether a relationship is perceived between knowledge about the older adult population and motivation to work with this population group. METHODS: Two discussion groups with students and three interviews with experts were conducted. Discussion groups and interviews were transcribed verbatim and analyzed through a reflexive thematic analysis, following the steps described by Braun and Clarke (2021). RESULTS: Three themes were identified from the discussion groups: (1) conception and ideas about older adults, (2) skills and knowledge perceived as important, and (3) proposals for motivational intervention addressed to the older population. Four themes were identified from the interviews with experts: (1) characteristics of the future professional, (2) physical activity programs for older people: the recipe for success, (3) the role of enjoyment as key to success, and (4) barriers/obstacles along the path. CONCLUSION: Students of both degrees and experts believe that more practical training opportunities are needed, to enable students to interact with the older population and get to know their needs, motivations, and barriers, to increase physical activity levels in this population group.
Asunto(s)
Ejercicio Físico , Envejecimiento Saludable , Humanos , Ejercicio Físico/psicología , Masculino , Femenino , Envejecimiento Saludable/psicología , Adulto , Promoción de la Salud , Actitud del Personal de Salud , Anciano , Deportes , Conocimientos, Actitudes y Práctica en Salud , Motivación , Adulto Joven , Estudiantes del Área de la Salud/psicología , Persona de Mediana EdadRESUMEN
Prior research has revealed distinctive patterns of impaired language abilities across the three variants of Primary Progressive Aphasia (PPA): nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). However, little is known about whether, and to what extent, non-verbal cognitive abilities, such as processing speed, are impacted in PPA patients. This is because neuropsychological tests typically contain linguistic stimuli and require spoken output, being therefore sensitive to verbal deficits in aphasic patients. The aim of this study is to investigate potential differences in processing speed between PPA patients and healthy controls, and among the three PPA variants, using a brief non-verbal tablet-based task (Match) modeled after the WAIS-III digit symbol coding test, and to determine its neural correlates. Here, we compared performance on the Match task between PPA patients (n = 61) and healthy controls (n = 59) and across the three PPA variants. We correlated performance on Match with voxelwise gray and white matter volumes. We found that lvPPA and nfvPPA patients performed significantly worse on Match than healthy controls and svPPA patients. Worse performance on Match across PPA patients was associated with reduced gray matter volume in specific parts of the left middle frontal gyrus, superior parietal lobule, and precuneus, and reduced white matter volume in the left parietal lobe. To conclude, our behavioral findings reveal that processing speed is differentially impacted across the three PPA variants and provide support for the potential clinical utility of a tabled-based task (Match) to assess non-verbal cognition. In addition, our neuroimaging findings confirm the importance of a set of fronto-parietal regions that previous research has associated with processing speed and executive control. Finally, our behavioral and neuroimaging findings combined indicate that differences in processing speed are largely explained by the unequal distribution of atrophy in these fronto-parietal regions across the three PPA variants.