Brain functional and effective connectivity underlying the information processing speed assessed by the Symbol Digit Modalities Test.

Delayed Information Processing Speed (IPS) often underlies attention deficits and is particularly evident in patients with traumatic brain injury, Parkinson's disease, depression, dementia, and multiple sclerosis. Therefore, it is of interest to determine the brain network that is responsible for such essential cognitive function to understand IPS deficits and to develop effective rehabilitation programs. We assessed brain functional connectivity and effective connectivity during the performance of an adapted version of the Symbol Digit Modalities Test. Using dynamic causal modeling, we focused on obtaining a network model for IPS function in healthy subjects. Sixteen right-handed volunteers (seven women, age: 29.7 ±â€¯5.0 years) were included in the study after giving written consent for participating. Functional magnetic resonance images were acquired in a 3T scanner. According to our results, two systems interact during the IPS task performance. One is formed by frontoparietal and fronto-occipital networks, related to the control of goal-directed (top-down) selection for stimuli and response, while the second is composed of the temporoparietal and inferior frontal cortices, which are associated with stimulus-driven attention in the brain. Additionally, the default-mode network showed a significant correlation with networks positively associated with the task, mainly those related to visual detection and processing, indicating its relevant role in functional integration involving IPS. Therefore, an IPS-related network was proposed through a methodology that may be useful for future studies considering other cognitive functions and tasks, clinical groups, and longitudinal assessments.

Symbol Digit Modalities Test adaptation for Magnetic Resonance Imaging environment: A systematic review and meta-analysis.

BACKGROUND: The Symbol Digit Modalities Test (SDMT) is widely used for cognitive evaluation of information processing speed (IPS), required in many cognitive operations. Despite being unspecific for different neurological disorders, it is sensitive to assess impaired performance related to stroke, Parkinson's disease, traumatic brain injury, and multiple sclerosis. However, in addition to evaluate the presence and severity of IPS impairment, it is of interest to determine the localization and integration of brain regions responsible for the functions assessed by the SDMT. OBJECTIVE: To review the studies that adapted the SDMT to the magnetic resonance environment and obtain the brain areas associated with the performance of the task in healthy subjects with a meta-analysis. METHODOLOGY: A systematic review was performed using ten studies published between 1990 and 2017, and selected from four databases. All studies included participants of both genders and age between 18 and 50 years, used Functional Magnetic Resonance Imaging (fMRI) and SDMT adaptation and reported brain regions associated with the task. Six of them also reported the region coordinates in a standard space, so they were included in a meta-analysis. Activation Likelihood Estimation algorithm, with significance for p < 0.05 corrected for multiple comparisons, was used to identify areas that are robustly related to the performance of the SDMT. RESULTS: The areas predominantly reported in the studies of our meta-analysis were regions of the frontoparietal attentional network and occipital cortex, as well as cuneus, precuneus, and cerebellum. Individually all regions that survived the statistical threshold are consistent with what is expected after reviewing prospective studies. CONCLUSIONS: The present study allowed the identification of brain areas activated during the performance of the SDMT in healthy subjects, and therefore it will help understanding the differences in brain activation by this task in clinical populations. Moreover, it may guide future studies of therapeutic strategies and interventions in those populations.

Cerebral blood flow and vasoreactivity in aging: an arterial spin labeling study.

Regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in young and elderly participants were assessed using pulsed arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) techniques in combination with inhalation of CO2. Pulsed ASL and BOLD-MRI were acquired in seventeen asymptomatic volunteers (10 young adults, age: 30±7 years; 7 elderly adults, age: 64±8 years) with no history of diabetes, hypertension, and neurological diseases. Data from one elderly participant was excluded due to the incorrigible head motion. Average baseline CBF in gray matter was significantly reduced in elderly (46±9 mL·100 g-1·min-1) compared to young adults (57±8 mL·100 g-1·min-1; P=0.02). Decreased pulsed ASL-CVR and BOLD-CVR in gray matter were also observed in elderly (2.12±1.30 and 0.13±0.06 %/mmHg, respectively) compared to young adults (3.28±1.43 and 0.28±0.11 %/mmHg, respectively; P<0.05), suggesting some degree of vascular impairment with aging. Moreover, age-related decrease in baseline CBF was observed in different brain regions (inferior, middle and superior frontal gyri; precentral and postcentral gyri; superior temporal gyrus; cingulate gyri; insula, putamen, caudate, and supramarginal gyrus). In conclusion, CBF and CVR were successfully investigated using a protocol that causes minimal or no discomfort for the participants. Age-related decreases in baseline CBF and CVR were observed in the cerebral cortex, which may be related to the vulnerability for neurological disorders in aging.

Impaired CBF regulation and high CBF threshold contribute to the increased sensitivity of spontaneously hypertensive rats to cerebral ischemia.

The correlation between temporal changes of regional cerebral blood flow (rCBF) and the severity of transient ischemic stroke in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) was investigated using T2-, diffusion- and perfusion-weighted magnetic resonance imaging at six different time points: before and during 1h of unilateral middle cerebral artery occlusion (MCAO), 1h after reperfusion, and 1 day, 4 days and 7 days after MCAO. rCBF values were measured in both hemispheres, and the perfusion-deficient lesion (PDL) was defined as the area of the brain with a 57% or more reduction in basal CBF. Within the PDL, regions were further refined as ischemic core (rCBF=0-6 mL/100 g/min), ischemic penumbra (rCBF=6-15 mL/100 g/min) and benign oligemia (rCBF>15 mL/100 g/min). SHR and WKY had identical initial volume of the PDLs (WKY: 32.52 ± 4.08% vs. SHR: 33.95 ± 3.68%; P>0.05) and the maximum rCBF measured within those lesions (WKY: 38.20 ± 3.57 mL/100g/min vs. SHR: 38.46 ± 6.22 mL/100 g/min; P>0.05) during MCAO. However, in SHR virtually all of the PDL progressed to become the final ischemic lesion (33.02 ± 5.41%, P>0.05), while the final ischemic lesion volume of WKY (12.62 ± 9.19%) was significantly smaller than their original PDL (P<0.01) and similar to the ischemic core (13.13 ± 2.96%, P>0.05). The region with the lowest range of rCBF was positively correlated with the final ischemic lesion volume (r=0.716, P<0.01). Both during ischemia and after reperfusion, rCBF in either ipsilesional and contralesional brain hemispheres of SHR could not be restored to pre-ischemic levels, and remained lower than in WKY until up to 4 days after MCAO. The data suggest that impaired CBF regulation and relatively high CBF threshold for ischemia are strong contributors to the increased susceptibility of SHR to ischemic stroke.

Quantitative evaluation of hemodynamic response after hypercapnia among different brain territories by fMRI.

The brain vascular system has an autoregulatory mechanism that maintains blood perfusion within normal limits at the capillary level. Partially due to its clinical importance, it is of interest to better understand the mechanisms involved in vascular regulation. Therefore, using functional magnetic resonance imaging (fMRI), we quantitatively investigated hemodynamic response characteristics of regions supplied by the main cerebral arteries, during two breath holding tests (BHT): after inspiration and after expiration. We used an auto-regressive method capable of estimating four signal parameters: onset delay, full width at half maximum (FWHM), time-to-peak and amplitude. The onset delay was significantly longer for the posterior cerebral artery (PCA) than for middle cerebral artery (MCA) and anterior arteries (ACA). FWHM and time-to-peak were larger in the ACA territory, indicating a slower blood flow in this region. Differences were also observed in the amplitude among the three areas, where MCA and PCA territories showed the smallest and the highest amplitudes, respectively. Moreover, differences were found in amplitude and onset when BHT was performed after inspiration as compared to BHT after expiration. Time-to-peak and FWHM showed no statistical differences between these two challenges. Such results are related to regional anatomical specificities and biochemical mechanisms responsible for vasodilation, such as those related to vascularity and vessel sizes.