OBJECTIVES: Treatment-resistant depression is a common clinical occurrence among patients with major depressive disorder (MDD), but its neurobiology is poorly understood. We used data collected as part of routine clinical care to study white matter integrity of the brain’s limbic system and its association to treatment response.
This paper presents a common stochastic modelling framework for physiological signals which allows patient simulation following a synthesis-by-analysis approach. Within this framework, we propose a general model-based methodology able to reconstruct missing or artifacted signal intervals in cardiovascular monitoring applications. The proposed model consists of independent stages which provide high flexibility to incorporate signals of different nature in terms of shape, cross-correlation and variability. The reconstruction methodology is based on model sampling and selection based on a wide range of boundary conditions, which include prior information. Results on real data show how the proposed methodology fits the particular approaches presented so far for electrocardiogram (ECG) reconstruction and how a simple extension within the framework can significantly improve their performance.
This paper presents a virtual model of patients with Deep Brain Stimulation implants. The model is based on Human Connectome and 7 Tesla Magnetic Resonance Imaging (MRI) data. We envision that the proposed virtual patient simulator will enable radio frequency power dosimetry on patients with deep brain stimulation implants undergoing MRI. Results from the proposed virtual patient study may facilitate the use of clinical MRI instead of computed tomography scans. The virtual patient will be flexible and morphable to relate to patient-specific neurological and psychiatric conditions such as Obsessive Compulsive Disorder, which benefit from deep brain stimulation.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.
We present work in progress on the virtual patient model for patients with Deep Brain Stimulation (DBS) implants based on Connectome and 7 Tesla Magnetic Resonance Imaging (MRI) data. Virtual patients are realistic computerized models of patients that allow medical-device companies to test new products earlier, helping the devices get to market more quickly and cheaply according to the Food and Drug Administration. We envision that the proposed new virtual patient simulator will enable radio frequency power dosimetry on patients with the DBS implant undergoing MRI. Future patients with DBS implants may profit from the proposed virtual patient by allowing for a MRI investigation instead of more invasive Computed Tomography (CT) scans. The virtual patient will be flexible and morphable to relate to neurological and psychiatric conditions such as Obsessive Compulsive Disorder (OCD), which benefit from DBS.
BACKGROUND: Obsessive-compulsive disorder (OCD) is a common and debilitating neuropsychiatric illness thought to involve abnormal connectivity of widespread brain networks, including frontal-striatal-thalamic circuits. At least half of OCD cases arise in childhood and their underlying neuropathology may differ at least in part from that of adult-onset OCD. Yet, only a few studies have examined brain white matter (WM) integrity in childhood-onset OCD using diffusion tensor imaging (DTI), and none have examined potential associations with age at onset. RESULTS: In this study, 17 youth with OCD and 19 healthy control subjects, ages 10 to 19 years, underwent DTI on a 3T Siemens scanner. DSM-IV diagnoses were established with standardized interviews, and OCD symptom severity was evaluated using the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Voxel-wise analyses were conducted on data processed with tract-based spatial statistics (TBSS) to derive measures of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). OCD patients had significantly lower FA in seven WM clusters, with over 80% of significant voxels in bilateral frontal cortex and corpus callosum (CC). There were no regions of significantly higher FA in patients compared with controls. Patients also had significantly higher RD in right frontal cortex and right body of the CC. Earlier age at onset of OCD correlated significantly with lower FA in the right thalamus and with higher RD in the right CC. FA and RD were not significantly associated with symptom severity. CONCLUSIONS: These findings point to compromised WM integrity and reduced myelination in some brain regions of children with OCD, particularly the CC and fiber tracts that connect the frontal lobes to widespread cortical and subcortical targets. They also suggest that age at onset may be a moderator of some of the WM changes in pediatric OCD.
BACKGROUND: Clues to the etiology and pathophysiology of schizophrenia can be examined in their first-degree relatives because they are genetically related to an ill family member, and have few confounds like medications. Brain abnormalities observed in young relatives are neurobiological indicators of vulnerability to illness. We examined the hypothesis that the hippocampus and parahippocampus are structurally abnormal and are related to default mode network (DMN) function and cognitive abnormalities in relatives of probands. METHODS: Subjects were 27 non-psychotic, first-degree relatives of individuals diagnosed with schizophrenia, and 48 normal controls, ages 13 to 28, undergoing high-resolution magnetic resonance imaging (MRI) at 1.5 T. After structural scan acquisition a subset of subjects performed 2-back working memory (WM) and 0-back tasks during functional MRI (fMRI) alternating with rest. fMRI data were analyzed using SPM-8. Volumes of total cerebrum, hippocampus, and parahippocampal gyrus were measured using semi-automated morphometry. RESULTS: Compared to controls, relatives had significantly smaller left hippocampi, without volumetric reduction in the parahippocampus. Relatives showed significantly less suppression of DMN activity in the left parahippocampal gyrus. Left hippocampal and posterior parahippocampal volumes were inversely and significantly associated with DMN processing (smaller volumes, less suppression) in relatives. Task suppression in parahippocampal gyrus significantly correlated with WM performance within the relatives. CONCLUSION: Results support the hypothesis that the vulnerability to schizophrenia includes smaller hippocampi and DMN suppression deficits, and these are associated with poorer WM. Findings suggest a primary structural, neurodevelopmental, medial temporal lobe abnormality associated with altered DMN function independent of psychosis.
Current research on concussion is primarily focused on injury identification and treatment. Prevention initiatives are, however, important for reducing the incidence of brain injury. This report examines the development and implementation of an interactive electronic teaching program (an e-module) that is designed specifically for concussion education within an adolescent population. This learning tool and the accompanying consolidation rubric demonstrate that significant engagement occurs in addition to the knowledge gained among participants when it is used in a school curriculum setting.
Measurements of water molecule diffusion along fiber tracts in CNS by diffusion tensor imaging (DTI) provides a static map of neural connections between brain centers, but does not capture the electrical activity along axons for these fiber tracts. Here, a modification of the DTI method is presented to enable the mapping of active fibers. It is termed dynamic diffusion tensor imaging (dDTI) and is based on a hypothesized "anisotropy reduction due to axonal excitation" ("AREX"). The potential changes in water mobility accompanying the movement of ions during the propagation of action potentials along axonal tracts are taken into account. Specifically, the proposed model, termed "ionic DTI model", was formulated as follows. First, based on theoretical calculations, we calculated the molecular water flow accompanying the ionic flow perpendicular to the principal axis of fiber tracts produced by electrical conduction along excited myelinated and non-myelinated axons.Based on the changes in molecular water flow we estimated the signal changes as well as the changes in fractional anisotropy of axonal tracts while performing a functional task.The variation of fractional anisotropy in axonal tracts could allow mapping the active fiber tracts during a functional task. Although technological advances are necessary to enable the robust and routine measurement of this electrical activity-dependent movement of water molecules perpendicular to axons, the proposed model of dDTI defines the vectorial parameters that will need to be measured to bring this much needed technique to fruition.
The brain morphometry of 21 children, who were followed from birth and underwent structural brain magnetic resonance imaging at 8-10 years, was studied. This cohort included 11 children with prenatal cocaine exposure (CE) and 10 noncocaine-exposed children (NCE). We compared the CE versus NCE groups using FreeSurfer to automatically segment and quantify the volume of individual brain structures. In addition, we created a pediatric atlas specifically for this population and demonstrate the enhanced accuracy of this approach. We found an overall trend towards smaller brain volumes among CE children. The volume differences were significant for cortical gray matter, the thalamus and the putamen. Here, reductions in thalamic and putaminal volumes showed a robust inverse correlation with exposure levels, thus highlighting effects on dopamine-rich brain regions that form key components of brain circuitry known to play important roles in behavior and attention. Interestingly, head circumferences (HCs) at birth as well as at the time of imaging showed a tendency for smaller size among CE children. HCs at the time of imaging correlated well with the cortical volumes for all subjects. In contrast, HCs at birth were predictive of the cortical volume only for the CE group. A subgroup of these subjects (6 CE, 4 NCE) was also scanned at 13-15 years of age. In subjects who were scanned twice, we found that the trend for smaller structures continued into teenage years. We found that the differences in structural volumes between the CE and NCE groups are largely diminished when the HCs are controlled for or matched by study design. Participants in this study were drawn from a unique longitudinal cohort and, while the small sample size precludes strong conclusions regarding the longitudinal findings reported, the results point to reductions in HCs and in specific brain structures that persist through teenage years in children who were exposed to cocaine in utero.
