“Need to know” and the right temporal lobe: Impaired access to semantic knowledge in acquired obsessive-compulsive disorder?

Introduction : Idiopathic obsessive-compulsive disorder (I-OCD) has been linked to abnormalities in corticostriatal circuits. Few studies have examined if the same structures are also responsible of acquired OCD (A-OCD) or if damage to anatomically-connected brain regions (e.g., temporal lobes) are also implicated in its pathogenesis. Additionally, there are some discrete obsessive-compulsive (OC) symptoms that by virtue of their presumed low occurrence and difficultly of categorization have received less attention. Amongst these, one intriguing and potentially severe type of obsessive thinking is the so-called “need to know” (NtK), a strong drive to know and obtain given information. In some patients this specific symptom, presumably resulting from impaired access to conceptual knowledge for specific verbal information (proper names, names of places), may be the principal or major feature of OCD symptomatology. We here report the cases of two male patients who developed “NtK” as the only OC symptomatology in association with malignant neoplasms involving the right temporal lobe and connected corticostriatal circuits. Methods : We used Tractotron and Disconnectome map softwares in order to identify the regions of white matter damage overlap across both patients and the proportion of damage (lesion load) of each tract of interest for each patient. We quantified the severity of the disconnection by measuring the proportion of each tract of interest to be affected by each patient´s lesion by using Tractotron software. Additionally, Positron Emission Tomography was used in order to study metabolic abnormalities. The tracts of interest were: the uncinate fasciculus, the anterior commissure, the anterior thalamic radiations, the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus. Results : There was a high overlap across brain lesions in patients 1 and 2. There was also a high overlap between areas that were affected (disconnected) due to the lesion. As expected, all the a priori selected pathways in the right hemisphere were affected since they cross the anterior part of the temporal lobe. Disconnection maps and metabolic changes in our patients suggest that the expression of OC symptoms underpinned by a semantic deficit due to right temporal damage is secondary to involvement of the uncinate fasciculus linking the temporal pole with the orbitofrontal cortex. Discussion : Data from the present study concur with previous research on A-OCD and current findings in I-OCD which suggest that the temporal lobes participate in the phenomenological expression of OCD. Also, patients with lesions in the anterior temporal lobe are prone to show a specific “Need to Know” symptoms phenomenologically similar to patients with semantic dementia in later stages. The expression of OC symptoms underpinned by a semantic deficit because of anterior right temporal lobe lesion, are due to a disconnection of the uncinate fasciculus and the orbitofrontal cortex. Further research about the neurological underpinnings of specific OCD subtypes, its evaluation and treatment, are essential. References : Berthier ML et al. Neurology. (1996) 47: 353–61. Huey E et al. J Neuropsych Clin Neurosci (2008). 20(4):390-408 Keywords : Emotions & Social Cognition; patients; single case study; adults; psychiatric; lesion mapping, behavioural.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

From dysfunctional to extraordinary verbal repetition abilities: clinical implications and neural features

Three cases are presented to index the hypothesis that mitigated echolalia emerges from overreliance on the dorsal language stream, through the arcuate fasciculus, when the ventral stream is damaged; whereas conduite d’approche ensues when the ventral stream attempts to compensate a dorsal damage. The role of the right hemisphere and other alternative pathways in both cerebral hemispheres in the successful compensation of brain injury is also discussed. Further, Study 2 reconceptualizes different types of echolalia within a continuous of severity and communication capacity. To accomplish this new instantiation, it is proposed that different types of echolalia may be associated to failure in distinctive linguistic and non-linguistic cognitive functions. Recommendations for its evaluation and treatment are provided, suggesting that echolalia interfering with functional communication should be treated. Further, complementing the previous one, Study 3 reports a comprehensive single case study exploring response to treatment, and behavioral and neuroimaging features of a person with mitigated echolalia associated to a chronic fluent aphasia. Findings from such case include a reduction of mitigated echolalia after two weeks of intensive aphasia therapy as well as the maintenance of these gains with memantine alone for at least 6 months. Importantly, reduction of mitigated echolalia instances in response to treatment speeded up the time needed to complete comprehension tasks. Neuroimaging results, although indirectly, suggested that mitigated echolalia may be supported by the activity of the remaining components of the left dorsal stream and compensatory right hemisphere recruitment. Additionally, to further explore the neural and cognitive mechanisms involved in verbal repetition in a model of language expertise, Study 4 tackles cognitive features and neural correlates of verbal expertise in two healthy adult subjects displaying an extraordinary ability to orally reverse language, a condition referred to as backward speech. Results suggest that phonological expertise, as shown in backward speech, involves reshaping (or pre-existent differences) of cortical areas and tracts relevant for auditory-motor integration and semantic processing. Greater functional coupling between critical language areas and domain-general and high-order visual areas may further support reversing processes. Lastly, Study 5 presents a systematic review of the literature aimed to examine sex differences in the prevalence of repetition deficits in persons with post-stroke aphasia. Results show that the proportion of females in the group of aphasia characterized by repetition deficits (i.e., conduction aphasia) is lower than the expected by the prevalence of stroke among them. It is suggested that sex-related differences in the volume of areas of the right hemisphere homologues to the ones subserving repetition in the left hemisphere may be at the base of this difference. This finding poses sex as a relevant variable to account for variance in repetition abilities, and as a relevant factor to consider in future studies of language acquisition, maturation, and relearning promoted by aphasia therapy. Fecha de lectura de Tesis Doctoral: 16 de diciembre 2019Verbal repetition and audio-visual imitation stand as crucial functions for the acquisition and maturation of language in childhood, language learning in adulthood, and a major resource for language recovery after brain damage. Although modern neuroimaging techniques have allowed the identification of the brain areas involved in repetition tasks in healthy subjects, many clinical and neural aspects of this linguistic function are still overlooked in persons with aphasia and in emerging models of language expertise. Therefore, the present dissertation aims to explore cognitive correlates and neural features of verbal repetition from different perspectives including models of dysfunctional repetition (i.e., people with aphasia) and language expertise (i.e., healthy backward speakers). Generally, this thesis explores the potential of the dorsal and ventral components of the neural network supporting verbal repetition to assume, under certain circumstances (e.g., brain damage or extraordinary abilities), non-canonical functions. Further, this dissertation addresses clinical issues of some aphasic symptoms characterized by uncontrolled repetition (i.e., echolalia), as well as reviews sex as a source of variability in verbal repetition outcomes after brain damage. This dissertation includes five studies that are part of this dissertation. First, it reviews the mechanisms involved in dysfunctional repetition, especially in two repetitive verbal behaviors named conduite d’approche and mitigated echolalia (Study 1) and addresses clinical issues of the last one (Study 2 and 3). In this regard, Study 1 proposes that in the context of aphasia these symptoms (i.e., conduite d’approche and mitigated echolalia) may represent active attempts of verbal communication, rather than inconsequential repetitive verbal behaviors resulting from maladaptive neural changes

Contribution of Xenopus model to a better understanding of cardiac outflow tract

Contribution of Xenopus model to a better understanding of cardiac outflow tract. A Torres-Prioris 1, SJ Smith 2, TJ Mohun 2, B Fernández 1, AC Durán 1. 1 Department of Animal Biology, Faculty of Science, and Biomedical Research Institute of Málaga (IBIMA), University of Málaga, Spain. 2 Developmental Biology Division, The Francis Crick Institute, Mill Hill Laboratory, London, UK. The morphology and morphogenesis of the cardiac outflow tract is a major topic in the study of the vertebrate circulatory system, especially regarding the pathologies affecting this region in humans. Recent studies have demonstrated that, in fish, the cardiac outflow tract consists of a myocardial conus arteriosus and a nonmyocardial bulbus arteriosus. Moreover, the bulbus arteriosus of fish has been considered homologous to the intrapericardial base of the aortic and pulmonary trunks of birds and mammals. Under this perspective, we have conducted a study on the outflow tract of Xenopus laevis, using histological, immunohistochemical and 3D reconstruction techniques. It has been assumed that the outflow tract of Xenopus, which is intercalated between the ventricle and the great arterial trunks, is of myocardial nature. At its luminal side, it contains two sets of valves between which the so-called spiral valve lies. Our results demonstrate that, together with a proximal myocardial segment, a distal, nonmyocardial, intrapericardial segment is also present in amphibians. We propose that this distal segment, from which the pulmocutaneous and systemic arteries arise, is homologous to the bulbus arteriosus of fish. Therefore, the bulbus arteriosus is an evolutionarily conserved structure, which has become the aortic and pulmonary roots of birds and mammals. Our findings contribute to strengthening Xenopus as a good model to better understand the outflow tract morphology and evolution, and as an emerging model for studying human congenital heart diseases. This work was supported by CGL2010-16417, BES-2011-046901, Estancias Breves para FPI (2012, 2013) and FEDER funds.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. CGL2010-16417, BES-2011-046901, Estancias Breves para FPI (2012, 2013), FEDER funds

Neurobehavioral changes in people with post-stroke aphasia

At present, research on neurobehavioral disorders in people with post-stroke aphasia is scarce, especially in Spanish. The objective of this study is to design a new scale on neurobehavioral change, the Scale of Neurobehavioral Affectation in Aphasia (EANA, in Spanish) and to evaluate 14 people affected by chronic post-stroke aphasia (mean age: 51/ DT: 7.2) together with their main informants. At the same time, psychiatric (Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale, Stroke Aphasic Depression Questionnaire), cognitive (Mini Mental State examination, Informer Test) and functional instruments (Stroke and Aphaisa Quality of Life Scale and Barthel Index) have been used to provide a multidimensional description of the affected persons. The results show statistically significant neurobehavioral changes in multiple domains. According to the EANA, those affected with post-stroke aphasia communicate with less frequently, show more introversion, shyness, dependence and apathy, behave in a more infantile manner ("makes me grimaces"), in addition to showing heightened anxiety and impulsivity. Finally, the informants report more aggressive acts, both verbal (insults) and physical (throwing objects, hitting both objects as persons), that did not occur before the stroke. According to the psychiatric instruments, many of the affected cope with anxiety, agitation and apathy, as well as mild depression. At a cognitive level, affected individuals show mild to moderate deficits, especially in working memory and temporal orientation. Functionally most individuals maintain a medium-high level of functional independence in daily activities. These findings support the inclusion of recommendations for the routine assessment and management of neurobehavioral changes to help optimize long-term recovery in people with stroke and aphasia.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Estudio de la morfología y el desarrollo del tracto de salida cardíaco en Xenopus laevis. Implicaciones evolutivas.

La morfología y la morfogénesis del tracto de salida cardíaco (TSC) constituyen temas esenciales en el estudio del sistema circulatorio de los vertebrados. Los grupos animales empleados habitualmente en estas investigaciones han sido aves y mamíferos. En los últimos años, se están introduciendo nuevos modelos, como peces y anfibios, que añaden una perspectiva evolutiva. En la presente Tesis Doctoral se ha estudiado el TSC de Xenopus laevis, con los objetivos siguientes: (1) determinar la estructura de los elementos anatómicos que lo conforman, (2) averiguar si dichos componentes son equivalentes a los identificados en los elasmobranquios y los actinopterigios, (3) estudiar la morfogénesis los componentes del TSC de Xenopus para averiguar si son homólogos al cono arterioso (CA) y el bulbo arterioso (BA) de los elasmobranquios y los actinopterigios. En total se analizaron 18 corazones de individuos adultos, 1556 larvas y 42 individuos postmetamórficos. Se emplearon técnicas histoquímicas e inmunohistoquímicas para microscopía óptica, microscopía electrónica de barrido, reconstrucciones 3D e hibridación in situ. Las principales conclusiones derivadas del presente trabajo son: (1) Los datos morfológicos obtenidos en ejemplares adultos indican que el TSC está formado por dos componentes, uno proximal (CP) de naturaleza miocárdica y otro distal (CD), no miocárdico, que presenta musculatura lisa. Por tanto, siguiendo la nomenclatura adoptada en otros grupos de vertebrados, los términos para designar dichos componentes en los anfibios han de ser CA y BA, respectivamente. Además, desde el punto de vista histomorfológico, en una porción del TSC el CA y el BA se solapan. (2) En X. laevis el CA presenta en ambos extremos sendas hileras de válvulas y está recorrido internamente por la cresta espiral. En cada hilera se alinean cuatro válvulas. (3) Se han detectado melanóforos en el subepicardio de todas las cámaras cardíacas, exceptuando el seno venoso. (4) El estudio de la morfogénesis del TSC ha puesto de manifiesto que el BA se desarrolla tras la formación del CA embrionario. El patrón de expresión de genes específicos de linajes celulares indica que en la formación de la cresta espiral participan células derivadas de la cresta neural, mientras que en la del BA contribuye el campo cardíaco secundario. Además, la tabicación del BA tiene lugar con posterioridad a la formación de los troncos arteriales extrapericárdicos. Los resultados embriológicos relativos al desarrollo de los cojines endocárdicos sustentan la idea de que, en los anfibios, las válvulas conales se desarrollan por un proceso de transición epitelio-mesénquima. (5) Los datos obtenidos sugieren que el BA de los anfibios es homólogo a las porciones intrapericárdicas de la aorta y de la arteria pulmonar de las aves y los mamíferos. Las observaciones sobre la morfogénesis del BA indican que éste es un componente con entidad propia y no una prolongación de la aorta o una modificación de la porción cefálica del CA, como han propuesto las hipótesis clásicas. Además, que el CA y el BA, que han debido estar presentes desde el inicio de la historia evolutiva de los vertebrados gnatostomados, están conservados en los primeros tetrápodos

PIGMENTATION OF THE HEART IN THE BICHIR, POLYPTERUS SENEGALUS

El resumen aparece en el Program & Abstracts of the 10th International Congress of Vertebrate Morphology, Barcelona 2013. Anatomical Record, Volume 296, Special Feature — 1: P-078.The presence of melanin-containing cells in the heart has been documented in tetrapods, but not in fish. It has been even suggested that dark pigmented cells are exclusively associated with hearts having two atria and two ventricles. The aim here is to report the occurrence of pigment cells in the heart of the bichir, an extant representative of the polypteriformes, an ancient ray-finned fish lineage that split from the stem of the actinopterygians soon after their divergence from the sarcopterygians. The bichir heart is composed of sinus venosus, atrium, ventricle, conus arteriosus and bulbus arteriosus arranged sequentially within the pericardial cavity. Dendritic-shaped cells containing melanosomes were found in the five cardiac components of the 12 bichirs included in this study. Numerous melanophores were distributed regularly over the surface of all segments having myocardium in their walls, thus resulting in a marked pigmentation of the whole heart. The bulbus arteriosus, which in the bichir is reduced in size, showed an even more intense pigmentation. In all instances, the melanophores were localized in the subepicardial space. Pigment cells also occurred in the pericardium and ventral aorta. The functional role of melanocytes in the tetrapod heart remains obscure. Antiinflamatory activity, cytoprotection and effects on the viscoelastic properties of the cardiac tissue have been adduced as possible actions of such cells. The role of pigment cells in the bichir heart constitutes a new open question. Interestingly, however, the only cells that have been shown to form melanin-containing cells in the heart derive from the neural crest. If the melanophores of the bichir heart are indeed of neural crest origin, it would suggest a much more extensive contribution and persistence of elements from the neural crest in the primitive heart of jawed vertebrates as assumed so far in most papers devoted to vertebrate heart embryology.Proyecto CGL2010-16417/BOS; Fondos FEDER; Beca FPI ref. BES-2011-046901

DISTRIBUTION OF PIGMENT CELLS IN THE HEART OF THE RABBITFISH, CHIMAERA MONSTROSA (CONDRICHTHYES: HOLOCEPHALI)

El resumen aparece en el Program & Abstracts of the 10th International Congress of Vertebrate Morphology, Barcelona 2013. Anatomical Record, Volume 296, Special Feature — 1: P-076.The study of extracutaneous cells producing and storing melanin is of interest because it may provide valuable information about the presence of neural crest elements in internal organs and tissues. Here we report, for the first time, the presence and distribution of melanophores in the heart of a chondrichthyan species, the rabbitfish, Chimaera monstrosa. Pigment cells were found in all of 20 hearts examined. Pigment cells occur mainly in the cardiac outflow tract, which consists of two anatomical components, the proximal, myocardial conus arteriosus and the distal, non-myocardial bulbus arteriosus. A few groups of dark pigmented cells were found in the apex of the ventricle of one specimen and in the atrium of two specimens. In all instances, the melanophores were located in the subepicardial space, where they could be well recognized in both unstained and stained histological sections. The distribution and intensity of the pigmentation in the cardiac outflow tract varies markedly between individuals. In all cases, however, the pigmented area is larger on the dorsal than on the ventral surface. Dorsally, the size of the pigmented area ranges from a fringe that includes the bulbus and the distal part of the conus to the whole surface of the outflow tract. Ventrally, the pigmented area does not cover the entire conus arteriosus. The intensity of the pigmentation also varies widely; in general, it is highest at the distal portion of the conus. There is no relationship between the distribution and intensity of the pigmentation and the sex and age of the animals. The functional role of the pigmented cells is unknown. If the melanophores in the heart of C. monstrosa are indeed of neural crest origin, it would suggest a notable contribution of the neural crest cells to the cardiac outflow tract in holocephalans.Proyecto CGL2010-16417/BOS; Fondos FEDER BES-2011-04690

Conduite d'approche in conduction aphasia: Which psycholinguistic and experimental variables drive it – A case study.

Conduite d’approche (CdA) is a classic repetitive behavior reported frequently in persons with conduction aphasia, however, relatively little is known about it, both at the brain and cognitive level (e.g., whether it is a self-correcting mechanism based on comprehension or rather on production, Nickels and Howard, 1995; Ueno and Lambon-Ralph, 2013). In this work we address which psycholinguistic and experimental variables boost the occurrence of CdAs and are involved in reaching a successful CdA. Here we study ANC, a 79-year-old male with high sociocultural level who suffers from a reproduction conduction aphasia that caused frequent CdAs.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Práctica de laboratorio: Microscopía I

Presentación para apoyar el trabajo en el aula del alumnado del Grado en Educación Primaria en la primera sesión de las prácticas de laboratorio sobre microscopía

Aphasia with anatomical isolation of the language area: A reanalysis on the light of modern neuroimaging techniques

Introduction : Goldstein (1948) and Geschwind (1968), based in data derived from anatomical post-mortem studies, postulated that the disconnection of the perisylvian language areas (PSLA) from other cortical areas was responsible for impairments in spontaneous speech and language comprehension with preservation of verbal repetition and echolalia (isolation of speech area). Nevertheless, other mechanisms (right hemisphere or bilateral hypotheses) underlying echolalic repetition have been proposed. Herein, we examined the structure and function of the PSLAs in two cases of aphasia with echolalic repetition and isolation of the left PSLA. Methods : Two patients with chronic post-stroke aphasia associated to isolation of the left PSLA were studied. Both patients underwent cognitive-language assessment and multimodal imaging. In patient 1 (p1), structural MRI, diffusion tensor imaging (DTI), functional MRI (fMRI) during repetition of words and non-words, resting state fMRI (rsfMRI) were acquired, whereas only structural MRI was performed in patient 2 (p2). The Tractotron software was used to examine the severity of disconnection in each language-related white matter tract in both patients. We quantified the severity of the disconnection by measuring the proportion of each tract that was affected. 18FDG-PET was also acquired in both patients. Results : P1 had a mixed transcortical aphasia and p2 had a transcortical sensory/anomic aphasia. In both, the MRI showed separate left anterior and posterior lesions with relative preservation of the PSLA. In both, 18FDG-PET revealed significant decrements of metabolic activity in areas of the left PSLA, although some parts showed normal metabolic activity. In p1 the left arcuate fasciculus (AF) and the inferior fronto-occipital fasciculi (IFOF) could not be reconstructed. fMRI showed perilesional activity in the left hemisphere and increased activity in the right during word repetition. rsfMRI showed compensatory activity in both hemispheres (right greater than left). Analysis with the Tractotron software revealed disconnection of both the AF and the IFOF in the left hemisphere of both patients. Discussion : Although some parts of the left PSLA had preserved metabolic activity in both patients, our neuroimaging data revealed that preserved repetition ability did not rely exclusively on the residual activity of the left PSLA. In support, the connectivity between different components of the left PSLA was severely affected. This coupled with the increased metabolic activity of the right PSLA supports the bilateral hypothesis of residual repetition in transcortical aphasias. References : Goldstein, K. (1948). Language and Language Disturbances. Geschwind, et al. (1968). Neuropsychologia 6, 327–340.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec