Wavelet correlation between subjects: A time-scale data driven analysis for brain mapping using fMRI

Functional magnetic resonance imaging (fMRI) based on BOLD signal has been used to indirectly measure the local neural activity induced by cognitive tasks or stimulation. Most fMRI data analysis is carried out using the general linear model (GLM), a statistical approach which predicts the changes in the observed BOLD response based on an expected hemodynamic response function (HRF). In cases when the task is cognitively complex or in cases of diseases, variations in shape and/or delay may reduce the reliability of results. A novel exploratory method using fMRI data, which attempts to discriminate between neurophysiological signals induced by the stimulation protocol from artifacts or other confounding factors, is introduced in this paper. This new method is based on the fusion between correlation analysis and the discrete wavelet transform, to identify similarities in the time course of the BOLD signal in a group of volunteers. We illustrate the usefulness of this approach by analyzing fMRI data from normal subjects presented with standardized human face pictures expressing different degrees of sadness. The results show that the proposed wavelet correlation analysis has greater statistical power than conventional GLM or time domain intersubject correlation analysis. (C) 2010 Elsevier B.V. All rights reserved.

Depression in Parkinson`s disease: Convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus

Depression is the most frequent psychiatric disorder in Parkinson`s disease (PD). Although evidence Suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontall cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation. (C) 2009 Elsevier Inc. All rights reserved.

Validation of ASHA FACS-Functional Assessment of Communication Skills for Alzheimer Disease Population

This study vas aimed to validate the American Speech-Language-Hearing Association Functional Assessment Of Communication Skills (ASHA FACS) for a Brazilian population. The scale was translated and adapted into Portuguese. Thirty-two patients with mild Alzheimer disease (AD). 25 patients with moderate AD. and 51 elderly without dementia were examined with Mini Mental State Examination, Geriatric Depression Scale. and Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-cog). The ASHA FACS was answered by their relative/caregiver. The scale`s internal consistency. its inter-examiner and intra-examiner`s reproducibility. and scale`s criterion validity were researched by correlation with ADAS-cog,. The sensitivity and specificity Were also researched. Statistical analyses indicated that the ASHA FACS has excellent internal consistency (Cronbach alpha = 0.955), test-retest reliability (interclass correlation coefficient = 0.995; P < 0.001). and inter-examiners (interclass correlation coefficient = 0.998: P < 0.001). It showed excellent criterion validity when correlated with ADAS-cog,. The ASHA FACS scale showed good sensitivity (75.0%) and specificity (82.4%) values once it is an ecologic and broad evaluation. The ASHA FACS Portuguese version is a valid and reliable instrument to verify communication alterations in AD patients and fills an important gap of efficiency indicators for speech language therapy in our country.

Six-minute walk test: functional capacity of severely obese before and after bariatric surgery

Background: The 6-minute walk test (6MWT) is a well-known instrument for assessing the functional capacity of a variety of groups, including the obese. It is a simple, low-cost and easily applied method to objectively assess the level of exercise capacity. The aim of the present study was to study the functional capacity of a severely obese population before and after bariatric surgery. Methods: A total of 51 patients were studied. Of the 51 patients, 86.2% were women, and the mean age was 40.9 +/- 9.2 years. All 51 patients were evaluated preoperatively and 49 were evaluated 7-12 months postoperatively. The initial body mass index was 51.1 +/- 9.2 kg/m(2), and the final body mass index was 28.2 +/- 8.1 kg/m(2). All patients underwent Roux-en-Y gastric bypass. The 6MWT was performed in a hospital corridor, with patients attempting to cover as much distance as they could, walking back and forth for as long as possible within 6 minutes at their regular pace. The total distance, Borg Scale of perceived exhaustion, modified Borg dyspnea scale for shortness of breath, and physical complaints at the end of the test were recorded. In addition, the heart rate and respiratory frequency were assessed before and after the test. Results: The tolerance was good, and no injuries occurred at either evaluation. The patients` mean distance for the 6MWT was 381.9 +/- 49.3 m before surgery and 467.8 +/- 40.3 m after surgery (p < .0001). Similar results were observed for the other parameters assessed. Conclusion: The 6MWT provided useful information about the functional status of the obese patients undergoing bariatric surgery. A simple, safe, and powerful method to assess functional capacity of severely obese patients, the 6MWT is an objective test that might replace the conventional treadmill test for these types of patients. (Surg Obes Relat Dis 2009;5:540-543.) (C) 2009 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Profiles of functional deficits in mild cognitive impairment and dementia: benefits from objective measurement

The magnitude Of functional impairment that may indicate the threshold between MCI and incipient Alzheimer`s disease (AD) has not been clearly defined. The objective was to examine the pattern of functional impairment in the continuum MCI-AD. Eighty-nine older adults (32 cognitively unimpaired, 31 MCI, and 26 AD patients) were examined with the Brazilian version of the Direct Assessment of Functional Status (DAFS-BR) at a University-based memory clinic. MCI patients were sub-divided according to the progression to AD upon follow-up, and had baseline cognitive, functional and biological variables analyzed. MCI patients displayed mild deficits in functional abilities, with intermediate scores as compared to controls and AD. The DAFS-BR items that differentiated MCI from controls involved the ability to deal with finances and shopping skills. At baseline, scores obtained by MCI patients who converted to AD were not significantly different from scores of nonconverters. The magnitude of functional deficits was associated with AD-like pathological findings in the CSF. In conclusion, MCI patients present with early functional changes in complex, instrumental abilities that require the integrity of memory and executive functions. The objective measurement of the functional state may help identify older adults with increased risk of developing dementia in the MCI-AD continuum. (JINS, 2010, 16, 297-305.)

EVALUATION OF FUNCTIONAL GAIN OF THE ELBOW FOLLOWING STEINDLER SURGERY FOR BRACHIAL PLEXUS INJURY

Objective: To evaluate the gain in strength and range of motion after modified Steindler surgery of the elbow in patients with lesions of the upper trunk of the brachial plexus. Method: From 1998 to 2007, eleven patients with traumatic closed upper trunk lesion of the brachial plexus were studied. All the patients had development of at least 1 year of injury and degree of strength of elbow flexion ranging from M1 to M3. The patients underwent Steindler surgery with at least 6 months of follow-up. Pre- and post-operative assessments were carried out to determine gain in muscle strength, range of motion of the elbow, and DASH scale score. Results: Of the eleven patients studied, nine (82%) achieved a level of strength equal to or greater than M3 (MRC) with good functional recovery. Two (18%) reached strength level M2 (MRC). We observed that the patients had an average postoperative gain in range of motion of the elbow of 43.45 degrees. The average elbow flexion after surgery was 88 degrees. There was an improvement in elbow function, as demonstrated in the DASH Scale, in 81% of the patients studied. Conclusion: Modified Steindler surgery was effective in the treatment of patients with injuries of the upper trunk of the brachial plexus, with statistically significant gains in range of motion. In all the cases studied, there was some degree of gain in strength and range of elbow flexion, the gain being correlated with the initial muscle strength. Level of Evidence: Level II, prospective clinical trial.

Pain Relief and Functional Recovery in Patients with Complex Regional Pain Syndrome after Motor Cortex Stimulation

In addition to pain and neurovegetative symptoms, patients with severe forms of complex regional pain syndrome (CRPS) develop a broad range of symptoms, including sensory disturbances, motor impairment and dystonic posturing. While most patients respond to medical therapy, some are considered refractory and become surgical candidates. To date, the most commonly used surgical procedure for CRPS has been spinal cord stimulation. This therapy often leads to important analgesic effects, but no sensory or motor improvements. We report on 2 patients with pain related to CRPS and severe functional deficits treated with motor cortex stimulation (MCS) who not only had significant analgesic effects, but also improvements in sensory and motor symptoms. In the long term (27 and 36 months after surgery), visual analog scale pain scores were improved by 60-70% as compared to baseline. There was also a significant increase in the range of motion in the joints of the affected limbs and an improvement in allodynia, hyperpathia and hypoesthesia. Positron emission tomography scan in both subjects revealed that MCS influenced regions involved in the circuitry of pain. Copyright (C) 2011 S. Karger AG, Basel

Abnormal Left and Right Amygdala-Orbitofrontal Cortical Functional Connectivity to Emotional Faces: State Versus Trait Vulnerability Markers of Depression in Bipolar Disorder

Background: Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). Methods: Thirty-one BD (type 1; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. Results: The BD versus HC showed significantly greater right amygdala-OFC FC (p <= .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001). Conclusions: In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC-FA relationships in BID and HC require further study.

Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder

In social anxiety disorder (SAD), impairments in limbic/paralimbic structures are associated with emotional dysregulation and inhibition of the medial prefrontal cortex (MPFq. Little is known, however, about alterations in limbic and frontal regions associated with the integrated morphometric, functional, and structural architecture of SAD. Whether altered gray matter volume is associated with altered functional and structural connectivity in SAD. Three techniques were used with 18 SAD patients and 18 healthy controls: voxel-based morphometry; resting-state functional connectivity analysis; and diffusion tensor imaging tractography. SAD patients exhibited significantly decreased gray matter volumes in the right posterior inferior temporal gyrus (ITG) and right parahippocampal/hippocampal gyrus (PHG/HIP). Gray matter volumes in these two regions negatively correlated with the fear factor of the Liebowitz Social Anxiety Scale. In addition, we found increased functional connectivity in SAD patients between the right posterior ITG and the left inferior occipital gyrus, and between the right PHF/HIP and left middle temporal gyms. SAD patients had increased right MPFC volume, along with enhanced structural connectivity in the genu of the corpus callosum. Reduced limbic/paralimbic volume, together with increased resting-state functional connectivity, suggests the existence of a compensatory mechanism in SAD. Increased MPFC volume, consonant with enhanced structural connectivity, suggests a long-time overgeneralization of structural connectivity and a role of this area in the mediation of clinical severity. Overall, our results may provide a valuable basis for future studies combining morphometric, functional and anatomical data in the search for a comprehensive understanding of the neural circuitry underlying SAD. (C) 2011 Elsevier B.V. All rights reserved.

Matrix metalloproteinase-9 genotypes and haplotypes are associated with multiple sclerosis and with the degree of disability of the disease

Multiple sclerosis (MS) is an autoimmune disease causing severe neurological disability. This study was carried out in order to determine whether the MMP-9 C(-1562)T and (CA)(13-25) polymorphisms are associated with MS. A total of 165 patients (92 whites/73 mulattos) and 191 controls (96 whites/95 mulattos) were enrolled in the study. While no difference in C(-1562)T polymorphism was observed between MS and healthy subjects, (CA)(n) genotypes and alleles were associated with MS. Moreover, the haplotypes are not associated with MS but seem to be relevant to the clinical status of MS. Thus the (CA)(n) polymorphism may contribute to MS susceptibility, but C(-1562)T and (CA)(n) haplotypes may modulate disease severity. (c) 2009 Elsevier B.V. All rights reserved.

Validation of the Brazilian version of the quality of life scale for patients with Alzheimer`s disease and their caregivers (QOL-AD)

Quality of life (QOL) has been extensively studied in clinical trials and in research on chronic degenerative diseases and dementia. The aim of this study was to assess the reliability and construct validity of the Brazilian version of the QOL scale in Alzheimer`s disease (AD; QOL-AD). The QOL-AD was administered to 60 patients with mild or moderate AD and to their caregivers. The construct validation was accomplished through correlations amongst total scores of patients` and caregivers` reports on patients` quality of life (PQOL and C-PQOL, respectively), and data related to cognitive impairment, depressive symptoms, functional performance, behavioral disturbances and a generic instrument of quality of life (WHOQOL-brief), as well as correlation of total score of caregivers` reports on their own quality of life (CQOL) with the measurements cited above, QOL-AD patient reports, and depressive symptoms. The reliability was high for PQOL, C-PQOL, and CQOL versions (Cronbach`s alpha = 0.80, 0.83, and 0.86, respectively). We observed significant correlations in the construct validity of all three versions regarding the variables associated with the disease and also with WHOQOL-brief. The scale took, on average, six min for each version. The results indicate reliability and construct validity of the Brazilian version of the QOL-AD in the studied sample.

Relationship among eccentric hip and knee torques, symptom severity and functional capacity in females with patellofemoral pain syndrome

Objective: To determine the relationships between eccentric hip and knee torques, symptom severity and functional capacity in females with patellofemoral pain syndrome (PFPS). Design: Within-subject correlational study. Setting: University biomechanics laboratory. Participants: 10 females diagnosed with PFPS. Main outcome measures: Eccentric strength of the hip abductors and lateral rotators, and knee extensors were assessed using an isokinetic dynamometer. A 10-cm visual analog scale was used to determine usual knee pain in the last week. The Anterior Knee Pain Scale (AKPS) was used to determine the functional capacity of the patients. Results: The study found that the greater the eccentric knee extensor and hip lateral rotator torques, the higher the functional capacity of the patients (p = 0.02, r = 0.72; p = 0.02, r = 0.72). It was also shown that the greater hip lateral rotator torque, the less the usual pain reported in the last week (p = 0.004, r = -0.84). Despite the lack of statistical significance (p = 0.11), it was also found a modest negative relationship between the eccentric knee extensor torque and the usual pain reported in the last week (r = -0.56) that was considered clinically meaningful (d = 1.4). Conclusions: This study showed that eccentric knee extensor and hip lateral rotator torques were associated with functional capacity and pain level in females with PFPS. Further investigations should be carried out to verify the effects of an intervention program focused on the eccentric action of these muscles with respect to the symptoms in patients with PFPS. (C) 2011 Elsevier Ltd. All rights reserved.

Stability improvement of the fatty acid binding protein Sm14 from S. mansoni by Cys replacement: Structural and functional characterization of a vaccine candidate

The Schistosoma mansoni fatty acid binding protein (FABP), SmA, is a vaccine candidate against, S. mansoni and F hepatica. Previously, we demonstrated the importance of a correct fold to achieve protection in immunized animals after cercariae challenge [[10]. C.R.R. Ramos, R.C.R. Figueredo, T.A. Pertinhez, M.M. Vilar, A.L.T.O. Nascimento, M. Tendler, I. Raw, A. Spisni, P.L. Ho, Gene structure and M20T polymorphism of the Schistosoma mansoni Sm14 fatty acid-binding protein: structural, functional and immunoprotection analysis. J. Biol. Chem. 278 (2003) 12745-12751]. Here we show that the reduction of vaccine efficacy over time is due to protein dimerization and subsequent aggregation. We produced the mutants Sm14-M20(C62S) and Sm14M20(C62V) that, as expected, did not dimerize in SDS-PAGE. Molecular dynamics calculations and unfolding experiments highlighted a higher structural stability of these mutants with respect to the wild-type. In addition, we found that the mutated proteins, after thermal denaturation, refolded to their active native molecular architecture as proved by the recovery of the fatty acid binding ability. Sm14-M20(C62V) turned out to be the more stable form over time, providing the basis to determine the first 3D solution structure of a Sm14 protein in its apo-form. Overall, Sm14-M20(C62V) possesses an improved structural stability over time, an essential feature to preserve its immunization capability and, in experimentally immunized animals, it exhibits a protection effect against S. mansoni cercariae infections comparable to the one obtained with the wild-type protein. These facts indicate this protein as a good lead molecule for large-scale production and for developing an effective Sm14 based anti-helminthes vaccine. (C) 2008 Elsevier B.V. All rights reserved.

A simple, inexpensive and easily reproducible model of spinal cord injury in mice: Morphological and functional assessment

Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance, and significantly impacts life expectancy and quality. Animal models provide a good opportunity to test therapeutic strategies in vivo. C57BL/6 mice were subjected to laminectomy at T9 and compression with a vascular clip (30 g force, 1 min). Two groups were analyzed: injured group (SCI, n = 33) and laminectomy only (Sham, n = 15). Locomotor behavior (Basso mouse scale-BMS and global mobility) was assessed weekly. Morphological analyses were performed by LM and EM. The Sham group did not show any morphofunctional alteration. All SCI animals showed flaccid paralysis 24 h after injury. with subsequent improvement. The BMS score of the SCI group improved until the intermediate phase (2.037 +/- 1.198): the Sham animals maintained the highest BMS score (8.981 +/- 0.056). p < 0.001 during the entire time. The locomotor speed was slower in the SCI animals (5.581 +/- 0.871) than in the Sham animals (15.80 +/- 1.166), p < 0.001. Morphological analysis of the SCI group showed, in the acute phase, edema, hemorrhage, multiple cavities, fiber degeneration, cell death and demyelination. In the chronic phase we observed glial scarring, neuron death, and remyelination of spared axons by oligodendrocytes and Schwann cells. In conclusion, we established a simple, reliable, and inexpensive clip compression model in mice, with functional and morphological reproducibility and good validity. The availability of producing reliable injuries with appropriate outcome measures represents great potential for studies involving cellular mechanisms of primary injury and repair after traumatic SCI. (C) 2008 Elsevier B.V. All rights reserved.

Síndrome do X Frágil com variante de Dandy-Walker: estudo clínico das manifestações comunicativas orais e escritas

A síndrome do X Frágil é a causa mais frequente de deficiência intelectual hereditária. A variante de Dandy-Walker trata-se de uma constelação específica de achados neurorradiológicos. Este estudo relata achados da comunicação oral e escrita de um menino de 15 anos com diagnóstico clínico e molecular da síndrome do X-Frágil e achados de neuroimagem do encéfalo compatíveis com variante de Dandy-Walker. A avaliação fonoaudiológica foi realizada por meio da Observação do Comportamento Comunicativo, aplicação do ABFW - Teste de Linguagem Infantil - Fonologia, Perfil de Habilidades Fonológicas, Teste de Desempenho Escolar, Teste Illinois de Habilidades Psicolinguísticas, avaliação do sistema estomatognático e avaliação audiológica. Observou-se: alteração de linguagem oral quanto às habilidades fonológicas, semânticas, pragmáticas e morfossintáticas; déficits nas habilidades psicolinguísticas (recepção auditiva, expressão verbal, combinação de sons, memória sequencial auditiva e visual, closura auditiva, associação auditiva e visual); e alterações morfológicas e funcionais do sistema estomatognático. Na leitura verificou-se dificuldades na decodificação dos símbolos gráficos e na escrita havia omissões, aglutinações e representações múltiplas com o uso predominante de vogais e dificuldades na organização viso-espacial. Em matemática, apesar do reconhecimento numérico, não realizou operações aritméticas. Não foram observadas alterações na avaliação audiológica periférica. A constelação de sintomas comportamentais, cognitivos, linguísticos e perceptivos, previstos na síndrome do X-Frágil, somada às alterações estruturais do sistema nervoso central, pertencentes à variante de Dandy-Walker, trouxeram interferências marcantes no desenvolvimento das habilidades comunicativas, no aprendizado da leitura e escrita e na integração social do indivíduo.