Synergistic associations of cognitive and motor impairments with functional outcome in covert cerebral small vessel disease

Background Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH). Methods Participants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation. Results Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single-leg stance, timed up-and-go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant-evaluated IADL, but not on self-evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance. Conclusion The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment.Peer reviewe

Anatomical atlas-guided diffuse optical tomography of brain activation

We describe a neuroimaging protocol that utilizes an anatomical atlas of the human head to guide diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median-nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject-specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of diffuse optical tomography images of brain activation.National Institutes of Health (U.S.) (U54-EB-005149)National Institutes of Health (U.S.) (P41-RR14075)National Institutes of Health (U.S.) (P41-RR13218

Muscles in “Concert”: Study of Primary Motor Cortex Upper Limb Functional Topography

BACKGROUND: Previous studies with Transcranial Magnetic Stimulation (TMS) have focused on the cortical representation of limited group of muscles. No attempts have been carried out so far to get simultaneous recordings from hand, forearm and arm with TMS in order to disentangle a 'functional' map providing information on the rules orchestrating muscle coupling and overlap. The aim of the present study is to disentangle functional associations between 12 upper limb muscles using two measures: cortical overlapping and cortical covariation of each pair of muscles. Interhemispheric differences and the influence of posture were evaluated as well. METHODOLOGY/PRINCIPAL FINDINGS: TMS mapping studies of 12 muscles belonging to hand, forearm and arm were performed. Findings demonstrate significant differences between the 66 pairs of muscles in terms of cortical overlapping: extremely high for hand-forearm muscles and very low for arm vs hand/forearm muscles. When right and left hemispheres were compared, overlapping between all possible pairs of muscles in the left hemisphere (62.5%) was significantly higher than in the right one (53.5% ). The arm/hand posture influenced both measures of cortical association, the effect of Position being significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2% with supine hand, but only for pairs of muscles belonging to hand and forearm, while no changes occurred in the overlapping of proximal muscles with those of more distal districts. CONCLUSIONS/SIGNIFICANCE: Larger overlapping in the left hemisphere could be related to its lifetime higher training of all twelve muscles studied with respect to the right hemisphere, resulting in larger intra-cortical connectivity within primary motor cortex. Altogether, findings with prone hand might be ascribed to mechanisms facilitating coupling of muscles for object grasping and lifting -with more proximal involvement for joint stabilization- compared to supine hand facilitating actions like catching. TMS multiple-muscle mapping studies permit a better understanding of motor control and 'plastic' reorganization of motor system

Effect of analysis strategy on reproducibility of detected fMRI activations

this paper is as follows [3]: First, as an initialization step the classification is initialized using Eq. (1). After the initialization, the voxels are re-classified. In the reclassification, a voxel is considered as active if z i + (u i 2) >T (2) and otherwise as non-active. Constant N n is the number of neighbors under consideration. By defining the neighborhood to consist of 26 closest voxels, N n =26. Variable u i is the number of currently active neighborhood voxels of voxel i . The parameter # determines the weighting of neighborhood information, and when positive, encourages neighbors to be of like class. One way to set the # is to write # = s . (3) Parameter s is a user specified parameter and may have any real positive value. Intuitively, s can be understood as a required excess of activated voxels (= u i 2) in the neighborhood of voxel i to transform a value of zero to the level of T . Classification rule (2) is repeated until convergence or oscillation between states occurs. During each iteration the classification and u i 's are updated. It is easy to see that as s approaches the contextual clustering approaches the voxel-by-voxel thresholding technique. As s approaches zero, the contextual clustering approaches a recursive majority vote classificatio

A contextual analysis method for multi-subject fMRI data

In this article, we present a novel approach to create single subject fMRI (functional magnetic resonance imaging) activation maps by utilizing the group data of several subjects on the individual level. Classification of a voxel as either activated or non-activated is based on its z-value and classification in the neighborhood. We defined the neighborhood of a voxel to consist of corresponding and neighboring voxels in two subjects in addition to the neighbourhood voxels within the subject itself. Determination of the two neighboring subjects was based on kappa-statistics between single subject activation maps calculated without data from other subjects. This approach was taken using multi-subject contextual clustering. Both fully simulated and real subject null data with simulated activations were used. ROC (receiver operator characteristics) analysis showed increased classification accuracy of activated and non-activated voxels when using the described approach.</p

Morphine-sparing Effect of Acetaminophen in Pediatric Day-case Surgery

Background. Postoperative pain is a major problem in daycase surgery in children. Nonsteroidal antiinflammatory drugs have gained popularity in management of pediatric surgical patients to reduce the need for opioids. The aim of this study was to evaluate the efficacy of different doses of rectal acetaminophen in day-case surgery in children. Methods: A randomized, double-blinded, placebo-controlled study design was used. Patients (n = 120) were randomized to receive a single dose of 0, 20, 40, or 60 mg/kg of rectal acetaminophen after induction of anesthesia. General anesthesia was induced by mask ventilation with sevoflurane (7%) in nitrous oxide and oxygen and maintained with 2.5-4.0% end-tidal sevoflurane. Opioids or local anesthetics were not used. Postoperative pain was evaluated by behavioral assessment and physiologic measurements every 10 min after arrival at the postanesthesia care unit. The pain intensity was scored using a 0-100 visual analog scale used in the authors&apos; clinic. The need for rescue medication, intravenous morphine 0.1 mg/kg, was decided by the nurse, who was unaware of the rectal acetaminophen dose. The parents were interviewed by phone after 24 h regarding pain and its treatment, nausea, and vomiting. Rescue analgesia at home was rectal ibuprofen, 10 mg/kg. Results: In the postanesthesia care unit pain scores were significantly lower in the 40-and 60-mg/kg groups compared with placebo and 2O-mg/kg groups. Acetaminophen resulted in a dose-related reduction in the number of children who r e quired postoperative rescue opioid, with significance reached with 40 or 60 mg/kg doses. Calculated dose of acetaminophen a

Global Burden of Small Vessel Disease–Related Brain Changes on MRI Predicts Cognitive and Functional Decline

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. / Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. / Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. / Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment