Shen-Hsing Annabel Chen

A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI studies

A growing interest in cerebellar function and its involvement in higher cognition have prompted much research in recent years. Cerebellar presence in a wide range of cognitive functions examined within an increasing body of neuroimaging literature has been observed. We applied a meta‐analytic approach, which employed the activation likelihood estimate method, to consolidate results of cerebellar involvement accumulated in different cognitive tasks of interest and systematically identified similarities among the studies. The current analysis included 88 neuroimaging studies demonstrating cerebellar activations in higher cognitive domains involving emotion, executive function, language, music, timing and working memory. While largely consistent with a prior meta‐analysis by Stoodley and Schmahmann ( : Neuroimage 44:489‐501), our results extended their findings to include music and timing domains to provide further insights into cerebellar involvement and elucidate its role in higher cognition. In addition, we conducted inter‐ and intradomain comparisons for the cognitive domains of emotion, language, and working memory. We also considered task differences within the domain of verbal working memory by conducting a comparison of the Sternberg with the n‐back task, as well as an analysis of the differential components within the Sternberg task. Results showed a consistent cerebellar presence in the timing domain, providing evidence for a role in time keeping. Unique clusters identified within the domain further refine the topographic organization of the cerebellum. Hum Brain Mapp 35:593–615, 2014.

Comparison of rhyming and word generation with FMRI

Functional magnetic resonance imaging (FMRI) has been successfully used to non‐invasively map language function, but has several disadvantages. These include severe motion sensitivity, which limits overt verbal responses in behavioral paradigms, such as word generation. The lack of overt responses prevents behavioral validation, making data interpretation difficult. Our objective was to compare the FMRI activation patterns of a novel silent rhyme determination task requiring a non‐verbal response, to covert word generation from visually presented letters. Five strongly right‐handed subjects performed both tasks during multi‐slice coronal echo‐planar T2*–weighted FMRI. Single subject activation maps were generated for each task by correlation analysis of single pixel time series to a boxcar reference function. These maps for the two tasks were separately interpolated to 2563, transformed into Talairach space, summed, and thresholded at t>6. Combined activation maps from both tasks showed similar robust perisylvian language area activation, including inferior frontal gyrus, posterior superior temporal lobe, and fusiform gyrus. Subjects performed well on the rhyming task, which activated left hemisphere cortical regions more selectively than the word generation task. The rhyming task showed less activation than the word generation task in areas typically not considered specifically related to language function, such as the dorsolateral prefrontal cortex and anterior cingulate. The rhyming task is a useful tool for brain mapping and clinical applications, potentially more specific to cortical language areas than verbal fluency. Hum. Brain Mapping 10:99–106, 2000.

A study of persistent post-concussion symptoms in mild head trauma using positron emission tomography.

Background: Complaints of persistent cognitive deficits following mild head trauma are often uncorroborated by structural brain imaging and neuropsychological examination. Objective: To investigate, using positron emission tomography (PET), the in vivo changes in regional cerebral uptake of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and regional cerebral blood flow (rCBF) in patients with persistent symptoms following mild head trauma. Methods: Five patients with mild head trauma and five age and education matched healthy controls were imaged using FDG-PET to measure differences in resting regional cerebral glucose metabolism. Oxygen-15 labelled water (H215O)-PET was also used to measure group differences in rCBF changes during a spatial working memory task. In addition, neuropsychological testing and self report of dysexecutive function and post-concussion symptoms were acquired to characterise the sample. Results: There was no difference between patients and controls in normalised regional cerebral FDG uptake in the resting state in frontal and temporal regions selected a priori. However, during the spatial working memory task, patients had a smaller increase in rCBF than controls in the right prefrontal cortex. Conclusions: Persistent post-concussive symptoms may not be associated with resting state hypometabolism. A cognitive challenge may be necessary to detect cerebral changes associated with mild head trauma.

The effectiveness of computer-assisted cognitive rehabilitation for persons with traumatic brain injury

This study examined the efficacy of computer-assisted cognitive rehabilitation (CACR) in persons with traumatic brain injury (TBI). Twenty persons with TBI who received hierarchically based CACR following inpatient neurorehabilitation were compared to a group of 20 persons with TBI matched for age, education, days in coma and time between testing. The comparison group received various other therapies including speech therapy and occupational therapy. The difference between pre- and post-treatment neuropsychological test scores was used to measure improvements in the domains of attention, visual spatial ability, memory and problem-solving. CACR and the comparison group showed significant post-treatment gains on the neuropsychological test scores, with CACR making significant gains on 15 measures and the comparison group on seven measures. However, we found no significant differences between the groups on their post-treatment gains. Results from this preliminary study found that, though significant cognitive gains were obtained after CACR, the extent and nature of these gains remains to be shown in controlled, prospective group studies.

A meta-analysis of fMRI studies on Chinese orthographic, phonological, and semantic processing

A growing body of neuroimaging evidence has shown that Chinese character processing recruits differential activation from alphabetic languages due to its unique linguistic features. As more investigations on Chinese character processing have recently become available, we applied a meta-analytic approach to summarize previous findings and examined the neural networks for orthographic, phonological, and semantic processing of Chinese characters independently. The activation likelihood estimation (ALE) method was used to analyze eight studies in the orthographic task category, eleven in the phonological and fifteen in the semantic task categories. Converging activation among three language-processing components was found in the left middle frontal gyrus, the left superior parietal lobule and the left mid-fusiform gyrus, suggesting a common sub-network underlying the character recognition process regardless of the task nature. With increasing task demands, the left inferior parietal lobule and the right superior temporal gyrus were specialized for phonological processing, while the left middle temporal gyrus was involved in semantic processing. Functional dissociation was identified in the left inferior frontal gyrus, with the posterior dorsal part for phonological processing and the anterior ventral part for semantic processing. Moreover, bilateral involvement of the ventral occipito-temporal regions was found for both phonological and semantic processing. The results provide better understanding of the neural networks underlying Chinese orthographic, phonological, and semantic processing, and consolidate the findings of additional recruitment of the left middle frontal gyrus and the right fusiform gyrus for Chinese character processing as compared with the universal language network that has been based on alphabetic languages.

Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: An integrative review

Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder.

Tract-Specific and Region of Interest Analysis of Corticospinal Tract Integrity in Subcortical Ischemic Stroke: Reliability and Correlation with Motor Function of Affected Lower Extremity

BACKGROUND AND PURPOSE: TS analysis has been suggested as a useful method to evaluate the fiber integrity of white matter tracts. This study investigated the intrarater and interrater reliability and validity of a TS analysis for the CST and compared the results with those of a ROI-based analysis. MATERIALS AND METHODS: Diffusion spectrum imaging was performed on 7 patients with subcortical ischemic stroke on a 3T MR imaging system. For the TS analysis, seed regions were placed at the cerebral peduncle and the medial portion of the primary motor cortex to reconstruct the tracts of the CST for motor control of the lower extremity. The mean GFA was measured at the PLIC by calculating the weighted sum of the GFAs sampled by the CST tracts at this segment. For the ROI-based analysis, the posterior two-thirds of the PLIC were enclosed on the GFA maps, and the mean GFA in this ROI was calculated. RESULTS: The results showed good-to-excellent intrarater and interrater reliability on the seed region/ROI placement (mean κ values >0.80) and mean GFA values (ICCs >0.90) for both the TS and ROI-based analyses. Both the GFAPLIC-TS and GFAPLIC-ROI values were highly correlated with the motor function of the affected lower extremity (r = 0.76 and 0.80, respectively; P < .05). CONCLUSIONS: We demonstrated good reliability and validity of the TS and ROI-based analyses of the CST corresponding to lower extremity motor control in patients with subcortical ischemic stroke.

Role of the premotor cortex in leg selection and anticipatory postural adjustments associated with a rapid stepping task in patients with stroke

The premotor cortex (PMC) plays an important role in selecting and preparing for movement. This study investigates how stroke-induced PMC lesions affect stepping leg selection and anticipatory postural adjustments (APAs) preparation. Fifteen hemi-paretic patients (eight with PMC lesions (PMC(Lesion)) and seven PMC spared (PMC(Spared))) and eight age- and sex-matched healthy adults participated in the study. The subjects performed rapid forward stepping with the right or left leg under simple and choice reaction time conditions. The percentage of trials in which the subject showed the correct initial vertical ground reaction force pattern before lift-off of the stepping leg indicated the accuracy in selecting the designated stepping leg. The latency of bilateral contractions in the tibialis anterior (TA) and the reaction time (RT) of the stepping leg represented the time needed to prepare for stepping-related APAs and stepping movement, respectively. All three groups demonstrated a similar rate of accuracy of the stepping leg selection under both conditions. However, in both conditions, the PMC(Lesion) group exhibited a longer RT and TA contraction latency of the affected leg than the healthy and PMC(Spared) groups. The PMC(Lesion) group also presented a longer TA contraction latency of the unaffected leg than the healthy group in both conditions. These results suggest that the PMC is involved in APAs associated with leg stepping movement and that a PMC lesion in one hemisphere impairs APAs of both the contralateral and ipsilateral legs during stepping.

Age-related vulnerabilities along the hippocampal longitudinal axis.

Evidence for an anterior‐posterior gradient of age‐related volume reduction along the hippocampal longitudinal axis has been reported in normal aging, but functional changes have yet to be systematically investigated. The current study applied an advanced brain mapping technique, large deformation diffeomorphic metric mapping (LDDMM), automatically delineating the hippocampus into the anterior and posterior segments based on anatomical landmarks. We studied this anterior‐posterior gradient in terms of structural and functional MRI in 66 participants aged from 19 to 79 years. The results showed age‐related structural volume reduction in both anterior and posterior hippocampi, with greater tendency for anterior decrease. FMRI task contrasts that robustly activated the anterior (associative/relational processing) and posterior (novelty) hippocampus independently, showed only significant reduction of activation in the anterior hippocampus as age increased. Our results revealed positive correlation between structural atrophy and functional decrease in the anterior hippocampi, regardless of task performance in normal aging. These findings suggest that anatomy and functions related to the anterior hippocampus may be more vulnerable to aging, than previously thought. Hum Brain Mapp 33:2415–2427, 2012.

Evolution of Hippocampal Shapes Across the Human Lifespan

Aberrant hippocampal morphology plays an important role in the pathophysiology of aging. Volumetric analysis of the hippocampus has been performed in aging studies; however, the shape morphometry—which is potentially more informative in terms of related cognition—has yet to be examined. In this paper, we employed an advanced brain mapping technique, large deformation diffeomorphic metric mapping (LDDMM), and a dimensionality reduction approach, locally linear diffeomorphic metric embedding (LLDME), to explore age‐related changes in hippocampal shape as delineated from magnetic resonance (MR) images of 302 healthy adults aged from 18 to 94 years. Compared with the hippocampal volumes, the hippocampal shapes clearly showed the nonlinear trajectory of biological aging across the human lifespan, where the variation of hippocampal shapes by age was characterized by a cubic polynomial. By integrating of LDDMM and LLDME, we were also able to illustrate the average hippocampal shapes in each individual decade. In addition, LDDMM and LLDME facilitated the identification of 63 years as a threshold beyond which hippocampal morphological changes were accelerated. Adults over 63 years of age showed the inward‐deformation bilaterally in the head of the hippocampi and the left subiculum regardless of hippocampal volume reduction when compared to adults younger than 63. Hence, we demonstrated that the shape of anatomical structures added another dimension of structural morphological quantification beyond the volume in understanding aging. Hum Brain Mapp 34:3075–3085, 2013.