Christian La

Alterations in regional homogeneity of resting‐state brain activity in mesial temporal lobe epilepsy

The purpose of the present study was to identify abnormal areas of regional synchronization in patients with mesial temporal lobe epilepsy and hippocampus sclerosis (mTLE‐HS) compared to healthy controls, by applying a relatively novel method, the Regional Homogeneity (ReHo) method to resting state fMRI (RS‐fMRI) data.

Functional connectivity changes in the language network during stroke recovery

Several neuroimaging studies have examined language reorganization in stroke patients with aphasia. However, few studies have examined language reorganization in stroke patients without aphasia. Here, we investigated functional connectivity (FC) changes after stroke in the language network using resting‐state fMRI and performance on a verbal fluency (VF) task in patients without clinically documented language deficits.

Regional homogeneity (ReHo) changes in new onset versus chronic benign epilepsy of childhood with centrotemporal spikes (BECTS): A resting state fMRI study.

OBJECTIVE The purpose of this study was to investigate regional homogeneity (ReHo) in children with new-onset drug-naïve Benign Epilepsy with Centrotemporal Spikes (BECTS), chronic BECTS and healthy controls (HC) using the Regional Homogeneity (ReHo) method applied to resting state fMRI data. METHODS Resting state fMRI data was collected from three groups of children aged 6-13, including new onset drug naïve BECTS, chronic BECTS with medication, and HC; the data analyzed by ReHo method. Mandarin school exams scores were acquired and compared across groups. RESULTS There were three main findings. Firstly, compared with HC, abnormally increased ReHo was observed in bilateral sensorimotor regions in new onset BECTS which normalized or even reversed in the chronic BECTS group. Secondly, enhanced ReHo was found in the left frontal language region in the two BECTS groups, with even higher ReHo value in the chronic group. Lastly, decreased ReHo was found in regions of the default mode network (DMN), bilateral occipital lobes and cerebellum in both the new onset and chronic BECTS groups, lower in chronic BECTS. Behavioral analyses of school scores showed the chronic BECTS group presented significantly lower scores compared to HC (p<.05). SIGNIFICANCE The coherence of low frequency fluctuations is disrupted in sensorimotor, language and DMN-related regions in new-onset BECTS. Some of these effects seem to be selectively normalized in chronic BECTS, thus allowing us to explore possible chronicity and AED-induced effects on BECTS. Abnormal ReHo in left language and DMN regions could be responsible for impairments of cognitive function.

Current Status and Future Perspectives of Magnetic Resonance High-Field Imaging: A Summary

There are several magnetic resonance (MR) imaging techniques that benefit from high-field MR imaging. This article describes a range of novel techniques that are currently being used clinically or will be used in the future for clinical purposes as they gain popularity. These techniques include functional MR imaging, diffusion tensor imaging, cortical thickness assessment, arterial spin labeling perfusion, white matter hyperintensity lesion assessment, and advanced MR angiography.

Differing Patterns of Altered Slow-5 Oscillations in Healthy Aging and Ischemic Stroke

The ‘default-mode’ network (DMN) has been investigated in the presence of various disorders, such as Alzheimer’s disease and Autism spectrum disorders. More recently, this investigation has expanded to include patients with ischemic injury. Here, we characterized the effects of ischemic injury in terms of its spectral distribution of resting-state low-frequency oscillations and further investigated whether those specific disruptions were unique to the DMN, or rather more general, affecting the global cortical system. With 43 young healthy adults, 42 older healthy adults, 14 stroke patients in their early stage (<7 days after stroke onset), and 16 stroke patients in their later stage (between 1 to 6 months after stroke onset), this study showed that patterns of cortical system disruption may differ between healthy aging and following the event of an ischemic stroke. The stroke group in the later stage demonstrated a global reduction in the amplitude of the slow-5 oscillations (0.01–0.027 Hz) in the DMN as well as in the primary visual and sensorimotor networks, two ‘task-positive’ networks. In comparison to the young healthy group, the older healthy subjects presented a decrease in the amplitude of the slow-5 oscillations specific to the components of the DMN, while exhibiting an increase in oscillation power in the task-positive networks. These two processes of a decrease DMN and an increase in ‘task-positive’ slow-5 oscillations may potentially be related, with a deficit in DMN inhibition, leading to an elevation of oscillations in non-DMN systems. These findings also suggest that disruptions of the slow-5 oscillations in healthy aging may be more specific to the DMN while the disruptions of those oscillations following a stroke through remote (diaschisis) effects may be more widespread, highlighting a non-specificity of disruption on the DMN in stroke population. The mechanisms underlying those differing modes of network disruption need to be further explored to better inform our understanding of brain function in healthy individuals and following injury.

Age-Related Changes in Inter-Network Connectivity by Component Analysis

Healthy aging is associated with brain changes that reflect an alteration to a functional unit in response to the available resources and architecture. Even before the onset of noticeable cognitive decline, the neural scaffolds underlying cognitive function undergo considerable change. Prior studies have suggested a disruption of the connectivity pattern within the “default-mode” network (DMN), and more specifically a disruption of the anterio-posterior connectivity. In this study, we explored the effects of aging on within-network connectivity of three DMN subnetworks: a posterior DMN (pDMN), an anterior DMN (aDMN), and a ventral DMN (vDMN); as well as between-network connectivity during resting-state. Using groupICA on 43 young and 43 older healthy adults, we showed a reduction of network co-activation in two of the DMN subnetworks (pDMN and aDMN) and demonstrated a difference in between-component connectivity levels. The older group exhibited more numerous high-correlation pairs (Pearsons rho > 0.3, Number of comp-pairs = 46) in comparison to the young group (Number of comp-pairs = 34), suggesting a more connected/less segregated cortical system. Moreover, three component-pairs exhibited statistically significant differences between the two populations. Visual areas V2–V1 and V2–V4 were more correlated in the older adults, while aDMN–pDMN correlation decreased with aging. The increase in the number of high-correlation component-pairs and the elevated correlation in the visual areas are consistent with the prior hypothesis that aging is associated with a reduction of functional segregation. However, the aDMN-pDMN dis-connectivity may be occurring under a different mechanism, a mechanism more related to a breakdown of structural integrity along the anterio-posterior axis.

Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions

Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the “default-mode” network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction (PPI) analysis demonstrated an independence of these two systems, with the onset of task not influencing the correlation between the two systems. Our results suggest that the language network and the DMN may be non-dependent systems, potentially correlated through the re-allocation of cortical resources, and that aging may affect those two systems differently.

Recovery of slow-5 oscillations in a longitudinal study of ischemic stroke patients

Functional networks in resting-state fMRI are identified by characteristics of their intrinsic low-frequency oscillations, more specifically in terms of their synchronicity. With advanced aging and in clinical populations, this synchronicity among functionally linked regions is known to decrease and become disrupted, which may be associated with observed cognitive and behavioral changes. Previous work from our group has revealed that oscillations within the slow-5 frequency range (0.01–0.027 Hz) are particularly susceptible to disruptions in aging and following a stroke. In this study, we characterized longitudinally the changes in the slow-5 oscillations in stroke patients across two different time-points. We followed a group of ischemic stroke patients (n = 20) and another group of healthy older adults (n = 14) over two visits separated by a minimum of three months (average of 9 months). For the stroke patients, one visit occurred in their subacute window (10 days to 6 months after stroke onset), the other took place in their chronic window (> 6 months after stroke). Using a mid-order group ICA method on 10-minutes eyes-closed resting-state fMRI data, we assessed the frequency distributions of a components representative time-courses for differences in regards to slow-5 spectral power. First, our stroke patients, in their subacute stage, exhibited lower amplitude slow-5 oscillations in comparison to their healthy counterparts. Second, over time in their chronic stage, those same patients showed a recovery of those oscillations, reaching near equivalence to the healthy older adult group. Our results indicate the possibility of an eventual recovery of those initially disrupted network oscillations to a near-normal level, providing potentially a biomarker for stroke recovery of the cortical system. This finding opens new avenues in infra-slow oscillation research and could serve as a useful biomarker in future treatments aimed at recovery.

Delay period activity of the substantia nigra during proactive control of response selection as determined by a novel fmri localization method

The ability to proactively control motor responses, particularly to overcome overlearned or automatic actions, is an essential prerequisite for adaptive, goal-oriented behavior. The substantia nigra (SN), an element of the BG, has figured prominently in current models of response selection. However, because of its small size and proximity to functionally distinct subcortical structures, it has been challenging to test the SNs involvement in response selection using conventional in vivo functional neuroimaging approaches. We developed a new fMRI localization method for directly distinguishing, on echo-planar images, the SN BOLD signal from that of neighboring structures, including the subthalamic nucleus (STN). Using this method, we tested the hypothesis that the SN supports the proactive control of response selection. We acquired high-resolution EPI volumes at 3 T from 16 healthy participants while they completed the Preparing to Overcome Prepotency task of proactive control. There was significantly elevated delay period signal selectively during high- compared with low-control trials in the SN. The STN did not show delay period activity in either condition. SN delay period signal was significantly inversely associated with task performance RTs across participants. These results suggest that our method offers a novel means for measuring SN BOLD responses, provides unique evidence of SN involvement in cognitive control in humans, and suggests a novel mechanism for proactive response selection.

Characterizing Recovery of the Human Brain following Stroke: Evidence from fMRI Studies

Abstract Stroke remains a major source of disability in the United States as well as in many industrialized countries. Although most patients survive acute stroke and some spontaneous recovery is common, the restoration of function is rarely complete, leaving persistent deficits that affect a patients activities of daily living. While the structural damage is usually rather localized, the functional damage can be vast, impacting regions physically remote from the area of infarct. Functional magnetic resonance imaging (fMRI) allows us to pursue, noninvasively, the investigation of stroke-related disruptions and brain recovery from such injuries. There is an emerging consensus from these fMRI studies in terms of the recovery process of the brain after a stroke. Task-based motor fMRI studies with patients exhibiting motor deficit have revealed initial recruitment of perilesional areas to the infarcted regions of the primary motor cortex as well as the homologous area in the contralesional hemisphere reaching high levels of activity at the subacute stages of recovery. The recruitment of such activity is thought to provide assistance initially in the execution of the motor functional task. This activity is then reduced in the later stages of recovery, mostly associated with further improvement of motor functions. Similarly, in patients exhibiting language deficit, perilesional areas to the infarcted regions of the language areas as well as the homologous areas in the contralesional hemisphere are recruited, reaching high levels of activity at the subacute stages of recovery and overall improvement of language function. This activity is then reduced in the later stages of recovery, mostly associated with further improvement of language functions. Although there is no clear consensus, most of these studies suggest a benefit of suppression of contralesional activation over time, which has shown promise in therapeutic rehabilitation strategies such as constraint-induced therapy and noninvasive brain stimulation methods. A third type of deficit that is common in stroke patients is hemispatial neglect caused by lesions that affect the directing of attention (the dorsal attention network). There is some fMRI evidence suggesting that recovery mechanisms within such a population involves reestablishment of the weighted activity within the dorsal attention network as well as involvement of a ventral attention network. Moreover, from analysis of networks in patients with stroke injury, interhemispheric connectivity initially disrupted by the onset of the injury is preferentially reestablished in the later stages if possible. Regaining of interhemispheric connectivity does not necessarily translate into increased activity, but rather translates into better communication between the two hemispheres, excitatory or inhibitory. There also exists a reestablishment of greater top-down modulatory control of higher level cortical areas on the lower cortices, such as premotor cortex exerting modulatory influence on the primary motor cortex in the motor system. Although the brain organization of a recovered patient returns to a “normal-like” pattern of activation with better recovery, graph theoretical analyses have demonstrated that neural reorganization after stroke may progress through the establishment of nonoptimal network structures, with the incorporation of previously unrecruited areas. Altogether, fMRI has consistently been proved to be a valuable and pragmatic tool in the investigation of the underlying mechanisms of stroke impairment and recovery. This allows us to hope that better treatment strategies will soon emanate and decrease the persistent burden that the injury of stroke imposes on the patient and society. Additionally, the use of fMRI provides several prospects in rehabilitation strategies such as future use of fMRI in real-time feedback modulation of neural activity in therapeutic protocols.