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BACKGROUND: Given the prevalence of adolescent depression and the modest effects of current treatments, research ought to inform development of effective intervention strategies. Self-compassion is inversely associated with depression, and self-compassion interventions have demonstrated promising effects on reducing depression. However, little is known about the neural mechanisms underlying that relationship. Maladaptive self-processing is a characteristic of depression that contributes to the onset and chronicity of depression. Because our own face is an automatic and direct cue for self-processing, this study investigated whether self-compassion was associated with neural responses during sad v. neutral self-face recognition and explore their relationship with depression severity in depressed adolescents and healthy controls (HCs). METHODS: During functional magnetic resonance imaging, 81 depressed youth and 37 HCs were instructed to identify whether morphed self or other faces with sad, happy, or neutral expressions resembled their own. RESULTS: Self-compassion correlated negatively with activity during sad v. neutral self-face recognition in the dorsal anterior cingulate cortex in the total sample, and in the right posterior cingulate cortex/precuneus in HCs, respectively. In depressed adolescents, higher self-compassion correlated with lower activity during sad v. neutral self-face recognition in the right dorsolateral prefrontal cortex (DLPFC), implying that less cognitive effort might be needed to avoid dwelling on sad self-faces and/or regulate negative affect induced by them. Moreover, higher self-compassion mediated the relationship between lower DLPFC activity and reduced depression severity. CONCLUSIONS: Our findings imply that DLPFC activity might be a biological marker of a successful self-compassion intervention as potential treatment for adolescent depression.
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Reconocimiento Facial , Adolescente , Corteza Prefontal Dorsolateral , Emociones/fisiología , Expresión Facial , Reconocimiento Facial/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Corteza Prefrontal/diagnóstico por imagen , AutocompasiónRESUMEN
BACKGROUND: Age, human immunodeficiency virus (HIV) infection, illicit drug use, and central nervous system (CNS) opportunistic infections can affect brain structure, with the striatum being particularly sensitive to HIV effects. Nevertheless, the impact of non-CNS AIDS-defining illness (ADI) on brain structure has been less investigated. We examined ADI and HIV effects on brain volume. METHODS: In a cross-sectional study, including 95 virally suppressed seropositive and 84 demographically matched, seronegative participants, we examined serostatus and ADI effects. Cortical and subcortical gray matter volume (GMV) regions of interest were estimated with computational neuroanatomy techniques applied to high-resolution, T1-weighted magnetic resonance imaging data. Linear regression was used to model HIV serostatus and ADI effects on global and regional GMV, adjusting for age, sex, CD4 nadir, drug use, and total intracranial volume. RESULTS: While HIV serostatus was associated with lower striatal volume (Bâ =â -.59 [95% confidence interval {CI},â -1.08 to -.10]), co-occurring ADI was independently associated with lower striatal volume (B = -.73 [95% CI, -1.36 to -.09]). ADI was also associated with lower global (B = -19.35 [95% CI, -32.42 to -6.29]) and regional GMV. CONCLUSIONS: While HIV infection is associated with a localized effect on striatal structure, having a prior ADI is a strong predictor of smaller global and regional GMV. The lack of interaction between HIV serostatus or ADI with age suggests that chronic HIV infection and ADI have independent effects on brain structure, without associated accelerated lower volume with age. ADI history should be incorporated into statistical adjustments in HIV neuroimaging analysis. These findings also lend support to current HIV treatment guidelines urging prompt antiretroviral therapy initiation after HIV diagnosis.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Encéfalo/diagnóstico por imagen , Estudios Transversales , Sustancia Gris/diagnóstico por imagen , Infecciones por VIH/complicaciones , Humanos , Imagen por Resonancia Magnética , NeuroimagenRESUMEN
OBJECTIVE: Consuming sweet foods, even when sated, can lead to unwanted weight gain. Contextual factors, such as longer time fasting, subjective hunger, and body mass index (BMI), may increase the likelihood of overeating. Nevertheless, the neural mechanisms underlying these moderating influences on energy intake are poorly understood. METHODS: We conducted both categorical meta-analysis and meta-regression of factors modulating neural responses to sweet stimuli, using data from 30 functional magnetic resonance imaging (fMRI) articles incorporating 39 experiments (N = 995) carried out between 2006 and 2019. RESULTS: Responses to sweet stimuli were associated with increased activity in regions associated with taste, sensory integration, and reward processing. These taste-evoked responses were modulated by context. Longer fasts were associated with higher posterior cerebellar, thalamic, and striatal activity. Greater self-reported hunger was associated with higher medial orbitofrontal cortex (OFC), dorsal striatum, and amygdala activity and lower posterior cerebellar activity. Higher BMI was associated with higher posterior cerebellar and insular activity. CONCLUSIONS: Variations in fasting time, self-reported hunger, and BMI are contexts associated with differential sweet stimulus responses in regions associated with reward processing and homeostatic regulation. These results are broadly consistent with a hierarchical model of taste processing. Hunger, but not fasting or BMI, was associated with sweet stimulus-related OFC activity. Our findings extend existing models of taste processing to include posterior cerebellar regions that are associated with moderating effects of both state (fast length and self-reported hunger) and trait (BMI) variables.
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Índice de Masa Corporal , Sacarosa en la Dieta/administración & dosificación , Hambre , Encéfalo/fisiología , Ingestión de Energía , Humanos , Imagen por Resonancia Magnética , Recompensa , GustoRESUMEN
BACKGROUND AND PURPOSE: Spontaneous visual recovery is rare after cortical blindness. While visual rehabilitation may improve performance, no visual therapy has been widely adopted, as clinical outcomes are variable and rarely translate into improvements in activities of daily living (ADLs). We explored the potential value of a novel rehabilitation approach "cognitive therapeutic exercises" for cortical blindness. CASE DESCRIPTION: The subject of this case study was 48-year-old woman with cortical blindness and tetraplegia after cardiac arrest. Prior to the intervention, she was dependent in ADLs and poorly distinguished shapes and colors after 19 months of standard visual and motor rehabilitation. Computed tomographic images soon after symptom onset demonstrated acute infarcts in both occipital cortices. INTERVENTION: The subject underwent 8 months of intensive rehabilitation with "cognitive therapeutic exercises" consisting of discrimination exercises correlating sensory and visual information. OUTCOMES: Visual fields increased; object recognition improved; it became possible to watch television; voluntary arm movements improved in accuracy and smoothness; walking improved; and ADL independence and self-reliance increased. Subtraction of neuroimaging acquired before and after rehabilitation showed that focal glucose metabolism increases bilaterally in the occipital poles. DISCUSSION: This study demonstrates feasibility of "cognitive therapeutic exercises" in an individual with cortical blindness, who experienced impressive visual and sensorimotor recovery, with marked ADL improvement, more than 2 years after ischemic cortical damage.Video Abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A173).
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Ceguera Cortical/psicología , Ceguera Cortical/rehabilitación , Terapia Cognitivo-Conductual , Terapia por Ejercicio , Actividades Cotidianas , Ceguera Cortical/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Recuperación de la Función , Visión Ocular , CaminataRESUMEN
BACKGROUND: Deficient empathic processing is thought to foster conduct disorder (CD). It is important to determine the extent to which neural response associated with perceiving harm to others predicts CD symptoms and callous disregard for others. METHODS: A total of 107 9- to 11-year-old children (52 female) were recruited from pediatric and mental health clinics, representing a wide range of CD symptoms. Children were scanned with functional magnetic resonance imaging while viewing brief video clips of persons being harmed intentionally or accidentally. RESULTS: Perceiving harm evoked increased hemodynamic response in the anterior insula (aINS), anterior cingulate cortex (ACC), amygdala, periaqueductal gray (PAG), caudate, and inferior parietal lobe (IPL) across all participants. Intentionally caused, relative to unintentional harm was associated with greater activity in the aINS, amygdala, and temporal pole. There was an inverse association of number of CD symptoms with right posterior insula in both the Harm > No Harm and the Intentional > Unintentional Harm contrasts. Furthermore, an inverse association between callousness and posterior insula activation was found in the Harm > No Harm contrast, with the opposite pattern for reactive aggression scores. An interaction revealed a stronger association in girls between CD symptoms and the right posterior superior temporal sulcus (pSTS) in the Intentional Harm versus Unintentional Harm contrast. CONCLUSIONS: Children with greater CD and callousness exhibit dampened hemodynamic response to viewing others being harmed in the insula, a region which plays a key role in empathy and emotional awareness. Sex differences in the neural correlates of CD were observed.
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Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Corteza Cerebral/fisiopatología , Trastorno de la Conducta/fisiopatología , Empatía/fisiología , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Factores SexualesRESUMEN
OBJECTIVE: We examined the preliminary acceptability and efficacy of family-based therapy (FBT) for weight restoration in young adults (FBTY) with Anorexia Nervosa (AN). METHOD: Twenty-two primarily female participants ranging from age 18 to 26, with AN or atypical AN (ICD-10) and their support adults were enrolled in a 6-month open trial of FBTY. Participants were assessed at baseline, after treatment, and at six and 12 month follow-up visits. The primary outcome was BMI and secondary outcomes included eating disorder psychopathology, current eating disorder obsessions, and compulsions, number of other Axis I disorders and global assessment of functioning. RESULTS: Although FBTY was rated as suitable by participants and their support adults, during FBTY, 9/22 participants dropped out and 3/22 dropped out at follow-up assessments. Despite being offered 18-20 sessions over six months, a mean of 12 FBTY sessions (SD = 6) were attended. After FBTY, 15 of the intent-to-treat sample of 22 were no longer underweight (BMIs ≥ 19 kg/m(2) ) and 12 months after treatment, 13/22 were no longer underweight. The magnitude of the BMI increase during FBTY (Hedges g = 1.20, 95th percentile CI = 0.55-1.85) was comparable to findings for adolescent FBT for AN. Secondary outcomes also improved. DISCUSSION: FBTY for young adults with AN and atypical AN, which involves support adults participants have chosen, results in weight restoration that is sustained up to a year after treatment. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:701-707).
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Anorexia Nerviosa/terapia , Terapia Familiar , Adolescente , Adulto , Anorexia Nerviosa/fisiopatología , Índice de Masa Corporal , Femenino , Humanos , Masculino , Resultado del Tratamiento , Aumento de Peso , Adulto JovenRESUMEN
Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.
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Encéfalo/fisiología , Meditación , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas , DescansoRESUMEN
OBJECTIVE: Anorexia Nervosa (AN) is associated with excessive self-control. This iterative case series describes the augmentation of Dialectical Behavior Therapy (DBT) for outpatient adult AN with skills addressing emotional and behavioral overcontrol. An overly controlled style is theorized to develop from the transaction between an individual with heightened threat sensitivity and reduced reward sensitivity, interacting with an environment reinforcing overcontrol and punishing imperfection. METHOD: Case Series 1 utilized standard DBT, resulting in retention of 5/6 patients and a body mass index (BMI) effect size increase of d = -0.5 from pre- to post-treatment. Case series 2, using standard DBT augmented with skills addressing overcontrol, resulted in retention of 8/9 patients with an effect size increase in BMI at post-treatment that was maintained at 6- and 12-months follow-up (d = -1.12, d = -0.87, and d = -1.12). DISCUSSION: Findings suggest that skills training targeting rigidity and increasing openness and social connectedness warrant further study of this model and treatment for AN.
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Anorexia Nerviosa/terapia , Terapia Conductista/métodos , Adulto , Atención Ambulatoria , Anorexia Nerviosa/psicología , Índice de Masa Corporal , Emociones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Proyectos de Investigación , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Although neuroimaging studies have revealed specific patterns of reorganization in the sensorimotor control network after stroke, their role in recovery remains unsettled. To review the existing evidence systematically, we performed activation likelihood estimation meta-analysis of functional neuroimaging studies investigating upper limb movement-related brain activity after stroke. METHODS: Twenty-four studies using sensorimotor tasks in standardized coordinates were included, totaling 255 patients and 145 healthy controls. Across the entire brain, we compared task-related activity patterns in good and poor recovery and assessed the magnitude of spatial shifts in sensorimotor activity in cortical motor areas after stroke. RESULTS: When compared with healthy controls, patients showed higher activation likelihood estimation values in contralesional primary motor soon after stroke that abated with time, but were not related to motor outcome. The observed activity changes were consistent with restoration of typical interhemispheric balance. In contrast, activation likelihood estimation values in ipsilesional medial-premotor and primary motor cortex were associated with good outcome, reorganization that may reflect vicarious processes associated with ventral activity shifts from BA4a to 4p. In the anterior cerebellum, a novel finding was the association of poor recovery with increased vermal activity, possibly reflecting behaviorally inadequate compensatory strategies engaging the fastigio-thalamo-cortical and corticoreticulospinal systems. CONCLUSIONS: Activity in ipsilesional primary motor and medial-premotor cortices in chronic stroke signals good motor recovery, whereas cerebellar vermis activity signals poor recovery. Functional MRI may be useful in identifying recovery biomarkers.
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Brazo/fisiología , Corteza Motora/fisiología , Trastornos del Movimiento/fisiopatología , Recuperación de la Función/fisiología , Accidente Cerebrovascular/fisiopatología , Isquemia Encefálica/fisiopatología , Cerebelo/fisiopatología , Enfermedad Crónica , Femenino , Lateralidad Funcional/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Corteza Somatosensorial/fisiología , Factores de TiempoRESUMEN
BACKGROUND: Depression is one of the most concerning mental disorders in youth. Because atypical excessive neural activity during self-referential processing is often implicated in depression, identifying psychological factors that link to lower depression and less excessive neural activity during self-referential processing is critical for treatment development. This study examined the relationship between self-compassion - a protective factor of youth depression - and neural activity during self-appraisals, a well-established experimental paradigm for studying self-referential processing, and their associations with depression severity in depressed and healthy youth. METHODS: The sample consisted of 115 youth (79 met the clinical diagnosis of depression; 36 were matched healthy controls) aged from 11 to 17 years (68 females). Self-compassion and depression severity were measured with self-reported scales. In the scanner, participants were asked to judge whether the phrases they heard described them from four perspectives (self, mother, classmate, and best friend). RESULTS: Higher self-compassion was associated with lower PCC/precuneus activity especially during negatively-valenced self-appraisals and explained its association with reduced depression severity. In depressed youth, higher self-compassion was associated with lower superior temporal gyrus/operculum/postcentral gyrus/insula activity especially during positively-valenced self-appraisals. In healthy youth, higher self-compassion was associated with higher activity in these regions. CONCLUSIONS: Self-compassion was associated with less excessive experiential immersion and/or autobiographical memory retrieval during negative self-appraisals. Neural stimulation interventions targeting PCC/precuneus activity during negative self-appraisals combined with behavioral interventions targeting self-compassion could be a promising approach to youth depression treatment.
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Autoevaluación Diagnóstica , Autocompasión , Femenino , Humanos , Adolescente , Madres , Lóbulo Parietal , Autoinforme , Depresión/psicología , EmpatíaRESUMEN
Autistics often exhibit enhanced perceptual abilities when engaged in visual search, visual discrimination, and embedded figure detection. In similar fashion, while performing a range of perceptual or cognitive tasks, autistics display stronger physiological engagement of the visual system than do non-autistics. To account for these findings, the Enhanced Perceptual Functioning Model proposes that enhanced autistic performance in basic perceptual tasks results from stronger engagement of sensory processing mechanisms, a situation that may facilitate an atypically prominent role for perceptual mechanisms in supporting cognition. Using quantitative meta-analysis of published functional imaging studies from which Activation Likelihood Estimation maps were computed, we asked whether autism is associated with enhanced task-related activity for a broad range of visual tasks. To determine whether atypical engagement of visual processing is a general or domain-specific phenomenon, we examined three different visual processing domains: faces, objects, and words. Overall, we observed more activity in autistics compared to non-autistics in temporal, occipital, and parietal regions. In contrast, autistics exhibited less activity in frontal cortex. The spatial distribution of the observed differential between-group patterns varied across processing domains. Autism may be characterized by enhanced functional resource allocation in regions associated with visual processing and expertise. Atypical adult organizational patterns may reflect underlying differences in developmental neural plasticity that can result in aspects of the autistic phenotype, including enhanced visual skills, atypical face processing, and hyperlexia.
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Trastorno Autístico/fisiopatología , Encéfalo/fisiología , Percepción Visual/fisiología , Mapeo Encefálico/métodos , Humanos , Modelos Neurológicos , Estimulación Luminosa/métodosRESUMEN
Physiological noise arising from a variety of sources can significantly degrade the detection of task-related activity in BOLD-contrast fMRI experiments. If whole head spatial coverage is desired, effective suppression of oscillatory physiological noise from cardiac and respiratory fluctuations is quite difficult without external monitoring, since traditional EPI acquisition methods cannot sample the signal rapidly enough to satisfy the Nyquist sampling theorem, leading to temporal aliasing of noise. Using a combination of high speed magnetic resonance inverse imaging (InI) and digital filtering, we demonstrate that it is possible to suppress cardiac and respiratory noise without auxiliary monitoring, while achieving whole head spatial coverage and reasonable spatial resolution. Our systematic study of the effects of different moving average (MA) digital filters demonstrates that a MA filter with a 2 s window can effectively reduce the variance in the hemodynamic baseline signal, thereby achieving 57%-58% improvements in peak z-statistic values compared to unfiltered InI or spatially smoothed EPI data (FWHM = 8.6 mm). In conclusion, the high temporal sampling rates achievable with InI permit significant reductions in physiological noise using standard temporal filtering techniques that result in significant improvements in hemodynamic response estimation.
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Encéfalo/fisiología , Neuroimagen Funcional/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Artefactos , Simulación por Computador , HumanosRESUMEN
Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups. Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention. Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests. Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.
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BACKGROUND: Numerous studies have used magnetic resonance spectroscopy (MRS) neurometabolite measurements to study HIV infection effects. While many have reported differences in total N-Acetylaspartate (tNAA), myo-Inositol (mI), and total Choline (tCho), there have been no meta-analyses performed to evaluate concordance across studies. PURPOSE: To evaluate the consistency of HIV serostatus effects on brain metabolites. STUDY SELECTION: The sample included studies conducted between 1993 and 2019 reporting HIV infection effects measured using proton MRS. tNAA/tCr ratios (21 papers), tCho/tCr ratios (21 papers), mI/tCr ratios (17 papers) and quantitative tCr (9 papers), sampling from basal ganglia (BG), gray matter (GM), and white matter (WM) were included. DATA ANALYSIS: Random effects meta-analysis using inverse variance weighting and bias corrected standardized mean differences (SMDs) was used. Meta-regression examined effects of publication year and data acquisition technique differences. DATA SYNTHESIS: BG SMDs related to positive serostatus were -0.10 [-0.39; 0.18] tNAA/tCr, 0.27 [0.05; 0.49] tCho/tCr, 0.60 [0.31; 0.90] mI/tCr, and -0.26 [-0.59; 0.06] tCr. GM SMDs related to serostatus were -0.29 [-0.49; -0.09] tNAA/tCr, 0.37 [0.19; 0.54] tCho/tCr, 0.41 [0.15; 0.68] mI/tCr, and -0.24 [-0.45; -0.03] tCr. WM SMDs related to serostatus were -0.52 [-0.79; -0.25] tNAA/tCr, 0.41 [0.21; 0.61] tCho/tCr, 0.59 [0.24; 0.94] mI/tCr, and -0.03 [-0.25; 0.19] tCr. WM regions showed larger serostatus effect sizes than BG and GM. I2 ranged from 52 to 88% for the metabolite ratios. Both GM and WM tNAA/tCr SMDs were lower with increasing calendar year. LIMITATIONS: Many studies pooled participants with varying treatment, infection, and comorbidity durations. CONCLUSIONS: HIV neurometabolite studies showed consistently lower tNAA/tCr, higher tCho/tCr and higher mI/tCr ratios associated with chronic HIV infection. Substantial between-study variation may have resulted from measurement technique variations, study population differences and HIV treatment changes over time. Higher WM tCho/tCr and mI/tCr may reflect reactive gliosis or myelin turnover. Neurometabolite measurements can reliably detect chronic HIV infection effects and may be useful in understanding the pathophysiology of cognitive and sensorimotor decline following HIV infection. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence of neurometabolite differences in chronic HIV infection.
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Infecciones por VIH , Ácido Aspártico , Encéfalo/diagnóstico por imagen , Colina , Creatina , Humanos , Inositol , Imagen por Resonancia Magnética , Espectroscopía de Resonancia MagnéticaRESUMEN
While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up. We enrolled patients aged 18-70 years less than 2 weeks following moderate-severe ischemic carotid stroke. Patients were randomized 2:1 to receive intravenous MSCs or not. Primary outcomes assessed feasibility and safety. Secondary outcomes assessed global and motor recovery. Passive wrist movement functional MRI (fMRI) activity in primary motor cortex (MI) was employed as a motor recovery biomarker. We compared "treated" and "control" groups using as-treated analyses. Of 31 enrolled patients, 16 patients received MSCs. Treatment feasibility was 80%, and there were 10 and 16 adverse events in treated patients, and 12 and 24 in controls at 6-month and 2-year follow-up, respectively. Using mixed modeling analyses, we observed no treatment effects on the Barthel Index, NIHSS, and modified-Rankin scores, but significant improvements in motor-NIHSS (p = 0.004), motor-Fugl-Meyer scores (p = 0.028), and task-related fMRI activity in MI-4a (p = 0.031) and MI-4p (p = 0.002). Intravenous autologous MSC treatment following stroke was safe and feasible. Motor performance and task-related MI activity results suggest that MSCs improve motor recovery through sensorimotor neuroplasticity. ClinicalTrials.gov Identifier NCT00875654.
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Autoinjertos , Isquemia Encefálica/terapia , Accidente Cerebrovascular Isquémico/terapia , Células Madre Mesenquimatosas/citología , Recuperación de la Función , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Trasplante de Células Madre Mesenquimatosas/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Tasks employing parametric variation in movement rate are associated with predictable modulations in neural activity and provide a convenient context for developing new techniques for system identification. Using a multistage approach, we explored the functional and effective connectivity of a visuomotor control system by combining generalized partial least squares (gPLS) with subsequent structural equation modeling (SEM) to reveal the relationships between neural activity and finger movement rate in an experiment involving visually paced left or right thumb flexion. The gPLS in the first analysis stage automatically identified spatially distributed sets of BOLD-contrast signal changes using linear combinations of sigmoidal basis functions parameterized by kinematic variables. The gPLS provided superior sensitivity in detecting task-related functional activity patterns via a step-wise comparison with both classical linear modeling and behavior correlation analysis. These activity patterns were used in the second analysis stage, which employed SEM to characterize the areal regional interactions. The hybrid gPLS/SEM procedure allowed modeling of complex regional interactions in a network including primary motor cortex, premotor areas, cerebellum, thalamus, and basal ganglia, with differential activity modulations with respect to rate observed in the corticocerebellar and corticostriate subsystems. This effective connectivity analysis of visuomotor control circuits showed that both the left and right corticocerebellar and corticostriate circuits exhibited movement rate-related modulation. The identification of the functional connectivity among regions participating particular classes of behavior using gPLS, followed by the estimation of the effective connectivity using SEM is an efficient means to characterize the neural interactions underlying variations in sensorimotor behavior.
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Encéfalo/fisiología , Modelos Neurológicos , Desempeño Psicomotor/fisiología , Percepción Visual/fisiología , Adolescente , Adulto , Algoritmos , Fenómenos Biomecánicos , Mapeo Encefálico , Femenino , Dedos , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Actividad Motora/fisiología , Vías Nerviosas/fisiología , Análisis de Regresión , Adulto JovenRESUMEN
Recent behavioral investigations have revealed that autistics perform more proficiently on Raven's Standard Progressive Matrices (RSPM) than would be predicted by their Wechsler intelligence scores. A widely-used test of fluid reasoning and intelligence, the RSPM assays abilities to flexibly infer rules, manage goal hierarchies, and perform high-level abstractions. The neural substrates for these abilities are known to encompass a large frontoparietal network, with different processing models placing variable emphasis on the specific roles of the prefrontal or posterior regions. We used functional magnetic resonance imaging to explore the neural bases of autistics' RSPM problem solving. Fifteen autistic and eighteen non-autistic participants, matched on age, sex, manual preference and Wechsler IQ, completed 60 self-paced randomly-ordered RSPM items along with a visually similar 60-item pattern matching comparison task. Accuracy and response times did not differ between groups in the pattern matching task. In the RSPM task, autistics performed with similar accuracy, but with shorter response times, compared to their non-autistic controls. In both the entire sample and a subsample of participants additionally matched on RSPM performance to control for potential response time confounds, neural activity was similar in both groups for the pattern matching task. However, for the RSPM task, autistics displayed relatively increased task-related activity in extrastriate areas (BA18), and decreased activity in the lateral prefrontal cortex (BA9) and the medial posterior parietal cortex (BA7). Visual processing mechanisms may therefore play a more prominent role in reasoning in autistics.
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Trastorno Autístico/fisiopatología , Mapeo Encefálico , Inteligencia/fisiología , Percepción Visual/fisiología , Adolescente , Adulto , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Pruebas de Inteligencia , Imagen por Resonancia Magnética , Masculino , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
While resting state fMRI (rs-fMRI) has gained widespread application in neuroimaging clinical research, its penetration into clinical medicine has been more limited. We surveyed a neuroradiology professional group to ascertain their experience with rs-fMRI, identify perceived barriers to using rs-fMRI clinically and elicit suggestions about ways to facilitate its use in clinical practice. The electronic survey also collected information about demographics and work environment using Likert scales. We found that 90% of the respondents had adequate equipment to conduct rs-fMRI and 82% found rs-fMRI data easy to collect. Fifty-nine percent have used rs-fMRI in their past research and 72% reported plans to use rs-fMRI for research in the next year. Nevertheless, only 40% plan to use rs-fMRI in clinical practice in the next year and 82% agreed that their clinical fMRI use is largely confined to pre-surgical planning applications. To explore the reasons for the persistent low utilization of rs-fMRI in clinical applications, we identified barriers to clinical rs-fMRI use related to the availability of robust denoising procedures, single-subject analysis techniques, demonstration of functional connectivity map reliability, regulatory clearance, reimbursement, and neuroradiologist training opportunities. In conclusion, while rs-fMRI use in clinical neuroradiology practice is limited, enthusiasm appears to be quite high and there are several possible avenues in which further research and development may facilitate its penetration into clinical practice.
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Brain imaging studies have explored the neural mechanisms of recovery in adults following acquired disorders and, more recently, childhood developmental disorders. However, the neural systems underlying adult rehabilitation of neurobiologically based learning disabilities remain unexplored, despite their high incidence. Here we characterize the differences in brain activity during a phonological manipulation task before and after a behavioral intervention in adults with developmental dyslexia. Phonologically targeted training resulted in performance improvements in tutored compared to nontutored dyslexics, and these gains were associated with signal increases in bilateral parietal and right perisylvian cortices. Our findings demonstrate that behavioral changes in tutored dyslexic adults are associated with (1) increased activity in those left-hemisphere regions engaged by normal readers and (2) compensatory activity in the right perisylvian cortex. Hence, behavioral plasticity in adult developmental dyslexia involves two distinct neural mechanisms, each of which has previously been observed either for remediation of developmental or acquired reading disorders.
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Corteza Cerebral/fisiopatología , Dislexia/rehabilitación , Lateralidad Funcional/fisiología , Educación Compensatoria/métodos , Adulto , Análisis de Varianza , Terapia Conductista , Mapeo Encefálico , Estudios de Casos y Controles , Corteza Cerebral/anatomía & histología , Corteza Cerebral/irrigación sanguínea , Dislexia/fisiopatología , Humanos , Pruebas del Lenguaje , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Fonética , Estimulación Física/métodos , Lectura , Resultado del Tratamiento , Conducta Verbal/fisiologíaRESUMEN
Accurate estimation of the timing of neural activity is required to fully model the information flow among functionally specialized regions whose joint activity underlies perception, cognition and action. Attempts to detect the fine temporal structure of task-related activity would benefit from functional imaging methods allowing higher sampling rates. Spatial filtering techniques have been used in magnetoencephalography source imaging applications. In this work, we use the linear constraint minimal variance (LCMV) beamformer localization method to reconstruct single-shot volumetric functional magnetic resonance imaging (fMRI) data using signals acquired simultaneously from all channels of a high density radio-frequency (RF) coil array. The LCMV beamformer method generalizes the existing volumetric magnetic resonance inverse imaging (InI) technique, achieving higher detection sensitivity while maintaining whole-brain spatial coverage and 100 ms temporal resolution. In this paper, we begin by introducing the LCMV reconstruction formulation and then quantitatively assess its performance using both simulated and empirical data. To demonstrate the sensitivity and inter-subject reliability of volumetric LCMV InI, we employ an event-related design to probe the spatial and temporal properties of task-related hemodynamic signal modulations in primary visual cortex. Compared to minimum-norm estimate (MNE) reconstructions, LCMV offers better localization accuracy and superior detection sensitivity. Robust results from both single subject and group analyses demonstrate the excellent sensitivity and specificity of volumetric InI in detecting the spatial and temporal structure of task-related brain activity.