Super- resolution of 3D MRI corrupted by heavy noise with the median filter transform

The acquisition of 3D MRIs is adversely affected by many degrading factors including low spatial resolution and noise. Image enhancement techniques are commonplace, but there are few proposals that address the increase of the spatial resolution and noise removal at the same time. An algorithm to address this vital need is proposed in this presented work. The proposal tiles the 3D image space into parallelepipeds, so that a median filter is applied in each parallelepiped. The results obtained from several such tilings are then combined by a subsequent median computation. The convergence properties of the proposed method are formally proved. Experimental results with both synthetic and real images demonstrate our approach outperforms its competitors for images with high noise levels. Moreover, it is demonstrated that our algorithm does not generate any hallucinations.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Language as a Threat: Multimodal Evaluation and Interventions for Overwhelming Linguistic Anxiety in Severe Aphasia

Linguistic anxiety (LA) is an abnormal stress response induced by situations that require the use of verbal behavior, and it is accentuated during language testing in persons with aphasia (PWA). The presence of LA in PWA may jeopardize the interpretation of cognitive evaluations, leading to biased conclusions about the severity of the language alteration and the effectiveness of the treatments. In the present study, we report the case of a woman (Mrs. A) with severe chronic mixed transcortical aphasia due to left frontal and parietal hemorrhages that partially spared the perisylvian area. Mrs. A was treated with the dopamine agonist Rotigotine alone and combined with Intensive Language-Action Therapy (ILAT). Complementary evaluations included autonomic reactivity during the performance of different language tasks, resting state functional magnetic resonance imaging (rs-fMRI) and [18F]-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). We found that formal language testing in a clinical setting triggered a dramatic increase of automatic echolalia, perseverations and frustration, making the task completion difficult. The treatment improved aphasia, but gains were more robust when evaluation was performed by Mrs. A’s husband at home than by clinicians. Autonomic evaluation under Rotigotine revealed higher reactivity during tasks tapping an impaired function in comparison with a task evaluating a preserved function (verbal repetition). Baseline 18F-FDG-PET analysis showed decreased metabolic activity in left limbic-paralimbic areas, whereas rs-fMRI revealed compensatory activity in the right hemisphere. We also analyzed the different factors (e.g., premorbid personality traits, task difficulty) that may have contributed to LA in Mrs. A during language testing. Our findings emphasize the usefulness of implicating adequately trained laypersons in the evaluation and treatment of PWA showing LA. Further studies using multidimensional evaluations are needed to disentangle the interplay between anxiety and abnormal language as well as the neural mechanisms underpinning LA in PWA

Ecolalia mitigada y conducta de aproximación: plasticidad compensatoria en los circuitos cerebrales de lenguaje

Introducción. Las descripciones tradicionales de afasia atribuyen las alteraciones lingüísticas a daño de tejido cerebral, principalmente en el hemisferio izquierdo. Esta es una explicación lógica para aquellos síntomas que implican alteración de las funciones lingüísticas previas (capacidad de comprensión reducida, anomia, etc.). Sin embargo, los síntomas caracterizados por errores (parafasias, perseveraciones, etc.) o repetición verbal excesiva (ecolalia), no pueden emanar de áreas totalmente disfuncionales. Dentro de estos, hay dos síntomas que se observan con frecuencia en personas con afasia (PcA): conduite d´approach (aproximaciones sucesivas a la palabra objetivo, [CdA]) y ecolalia mitigada (EM). Objetivo. Explorar los mecanismos funcionales y estructurales que sustentan la CdA y EM, y cómo estos se relacionan con cambios plásticos dentro de la red del lenguaje. Para este fin, presentamos datos comportamentales y de neuroimagen de 3 PcA crónica. El paciente 1 presentaba un lenguaje caracterizada por múltiples instancias de CdA, el paciente 2 presentaba predominantemente EM y el paciente 3 instancias de ambos síntomas. Conclusiones. La CdA parece reflejar actividad de la vía ventral del lenguaje tras daño de la vía dorsal, mientras que la EM refleja hiperactividad de la vía dorsal en un intento por compensar un daño en la vía ventral.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Is the emergence of speech errors in chronic post-stroke aphasia a result of ongoing compensatory brain plasticity mechanisms?

Traditional descriptions of aphasia have ascribed language disturbances to tissue damage but symptoms expressed as repetitive verbal behaviors such as echolalia, perseverations and so forth, cannot emanate from fully dysfunctional. We propose that in aphasia, repetitive verbal behaviors (such as conduite d’approche (CdA) and mitigated echolalia (ME)) may be compensatory behaviors emerging from ongoing plastic changes occurring in the preserved tissue. CdA is the repetitive and self-initiated approximation to a target word during spontaneous speech or naming tasks. ME refers to the echoing of a just heard sentence introducing a subtle change. At brain level, language deficits usually result from lesions affecting the dorsal and the ventral streams. Damage to the main dorsal pathway is related to deficits in verbal repetition and fluency, while lesions affecting the ventral pathway are related to comprehension deficits. Thus, we propose that ME may emerge from spared dorsal stream when the ventral system is compromised, while CdA may result as an attemp of the ventral stream to compensate dorsal damage. In this study we analysed three cases of aphasia at linguistic and structural (MRI and PET) levels. In patient 1, speech was predominantly characterized by instances of CdA, patient 2 presented predominantly ME instances, and patient 3 had both CdA and ME. Results showed that patient 1 had a disconnection pattern that greatly overlapped with the dorsal language pathway, while patient 2 ́s lesion location bisected the ventral pathway discontinuing the projection of fibers that run through it. Patient 3 presented a disconnection pattern in-between the two previous ones. These findings suggest that symptoms as CdA and ME, that frequently appear in the chronic stage of aphasia may represent the behavioral expression of plastic changes occurring within the preserved language network in an attempt to compensate the linguistic functions associated to the damaged pathway.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

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

Beneficial effects of pharmacological treatment in post-stroke dynamic aphasia: a behavioural and neuroimaging study

Introduction : Dynamic Aphasia (DA) is a rare form of language disorder characterized by reduced spontaneous speech with preservation of other language functions. Two types of DA have been described: language-specific type (type I DA) and domain-general type (type II DA). In type I DA, deficits are selective for word and sentence generation, whereas in type II DA impairments affect discourse generation, narrative, fluency, and non-verbal generation tasks. There is little information on the treatment of DA. Although treatment with a cognitive enhancing drug (bromocriptine) improved outcome in previous studies, pharmacological interventions combining two drugs acting on other neurotransmitter systems in DA have not been reported so far. Methods : We report an open-label pharmacological single case study (n = 1) in a male patient with a chronic type I/II DA secondary to an ischemic infarction in the left fronto-opercular and insular regions. After baseline evaluation, the patient received donepezil 5 mg/day (2 months), donepezil 10 mg/day (2 months), donepezil 10 mg/day plus memantine 20 mg/day (4½ months) followed by a washout period (1½ months). No speech-language therapy was used. A comprehensive cognitive and language evaluation was carried out at baseline and at different endpoints. 18FDG-PET was performed at the four timepoints. Results : Donepezil (5 mg/day) significantly improved type I DA features (normalization of verbs generation, p = 0.01), whereas donepezil (10 mg/day) improved some type II features (normalizing spontaneous speech, verbal fluency and improving generation of novel thoughts, p = 0.004), along with improvement of executive-attentional functioning. Combined therapy further enhanced cognitive function, but did not additionally improved DA. 18 FDG-PET revealed significant reductions of perilesional hypometabolic activity mainly after donepezil (10 mg/day) and washout. Discussion : Treatment with donepezil improved language deficits in a patient with chronic post-stroke type I/II DA. Combined therapy (donepezil plus memantine) further enhanced executive-attentional functioning. Beneficial changes were associated with improvements in perilesional metabolic activity. References : Luria AR et al.Acta Neurologica et Psychiatrica (1967). Robinson G et al. Brain (1998). Keywords : Language; patients; single case study; adults; cerebrovascular; behavioural, functional imaging.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

“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

Correlatos cerebrales y cognitivos de la potenciación farmacológica en un caso de afasia dinámica

Introducción. La afasia dinámica (AD) es un tipo raro de alteración del lenguaje caracterizada por una reducción del habla espontánea. La AD tipo lingüístico (AD I) se caracteriza por dificultades en la generación de palabras/frases, mientras que la AD tipo general (AD II) se caracteriza por problemas en la generación del discurso y la fluencia. Nuestro objetivo fue evaluar el efecto de dos fármacos combinados (donepezilo y memantina) que actúan sobre los sistemas de neurotransmisión colinérgico y dopaminérgico, respectivamente, en la recuperación de la AD. Descripción y resultados. Reportamos un estudio abierto de caso único de un paciente con AD I/II post-ictus. Se realizaron 5 evaluaciones cognitivas/lingüísticas y 18FDG-PET en 5 momentos: línea base, donepezilo-5mg/día (2 meses) , donepezilo-10mg/día (2 meses9, donepezilo-10mg/día más memantina-20mg/día (4½ meses) y período de lavado (1½ mes). Donepezilo-5mg/día mejoró la sintomatología de la AD I, mientras que el donepezilo-10mg/día mejoró la sintomatología AD II y las funciones ejecutivas/atencionales. El 18FDG-PET mostró un restablecimiento de la actividad metabólica perilesional después del donepezilo-10mg/día y del periodo de lavado. Conclusiones. El tratamiento con donepezilo mejoró los déficits lingüísticos en un paciente con AD I/II post-ictus. La terapia combinada produjo mejorías principalmente en funciones ejecutivas/atención, y estos beneficios, estaban asociados a mejorías de la actividad metabólica perilesional.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Neural signatures of treatment-induced benefits in apathy and depression amongst persons with aphasia

Intensive language-action therapy (ILAT) reduces symptoms of depression in persons with aphasia (PWA) due to stroke. The neural correlates of such improvement remain unexplored. Here we evaluated apathy and depression in PWA receiving treatment with the cholinesterase inhibitor donepezil (DP) alone and combined with ILAT as well as the brain changes promoted by these interventions. Ten PWA with chronic left perisylvian strokes participated in a 10-week open-label pilot study. They received DP alone (wk 0-8) and thereafter combined with ILAT (wk 8-10 30 hours, wks 8-10). Structural MRI and resting state [18]fluorodeoxyglucose PET (18FDG-PET) were acquired for at 3 time-points in order to measure grey matter density (Voxel-based morphometry, VBM) and metabolic changes. The primary outcome measures were: Aphasia Quotient of the Western Aphasia Battery (AQ-WAB), Communicative Activity Log (CAL), Stroke Aphasic Depression Questionnaire (SADQ), and Stroke and Aphasia Quality of Life Scale-39 (SAQoL-39). The 21-item SADQ was used to examine apathy (7 items) and depression (14 items). Significant improvements with DP alone and under DP-ILAT were seen in AQ-WAB, CAL and SAQoL-39. Improvements in symptoms of apathy and depression were observed when comparing DP-ILAT with baseline. 18FDG-PET analysis revealed that DP alone induced significant increments in metabolic activity in cortical and subcortical areas that correlated with improvement in apathetic and depressive symptoms. VBM analyses revealed that DP alone and combined DP-ILAT induced increases in grey matter density in areas of the right hemisphere previously associated to improvements in apathy and depression. In conclusion, treatment with DP alone and combined with ILAT improved aphasia, communication and quality of life as well as associated symptoms of apathy and depression by modulating regions innervated by the left medial, right lateral and brainstem cholinergic pathways.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Language as a Threat: Multimodal Evaluation and Interventions for Overwhelming Linguistic Anxiety in Severe Aphasia.

Linguistic anxiety (LA) is an abnormal stress response induced by situations that require the use of verbal behavior, and it is accentuated during language testing in persons with aphasia (PWA). The presence of LA in PWA may jeopardize the interpretation of cognitive evaluations, leading to biased conclusions about the severity of the language alteration and the effectiveness of the treatments. In the present study, we report the case of a woman (Mrs. A) with severe chronic mixed transcortical aphasia due to left frontal and parietal hemorrhages that partially spared the perisylvian area. Mrs. A was treated with the dopamine agonist Rotigotine alone and combined with Intensive Language-Action Therapy (ILAT). Complementary evaluations included autonomic reactivity during the performance of different language tasks, resting state functional magnetic resonance imaging (rs-fMRI) and [18F]-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). We found that formal language testing in a clinical setting triggered a dramatic increase of automatic echolalia, perseverations and frustration, making the task completion difficult. The treatment improved aphasia, but gains were more robust when evaluation was performed by Mrs. A's husband at home than by clinicians. Autonomic evaluation under Rotigotine revealed higher reactivity during tasks tapping an impaired function in comparison with a task evaluating a preserved function (verbal repetition). Baseline 18F-FDG-PET analysis showed decreased metabolic activity in left limbic-paralimbic areas, whereas rs-fMRI revealed compensatory activity in the right hemisphere. We also analyzed the different factors (e.g., premorbid personality traits, task difficulty) that may have contributed to LA in Mrs. A during language testing. Our findings emphasize the usefulness of implicating adequately trained laypersons in the evaluation and treatment of PWA showing LA. Further studies using multidimensional evaluations are needed to disentangle the interplay between anxiety and abnormal language as well as the neural mechanisms underpinning LA in PWA