Jen-Kai Chen

Retrosplenial and hippocampal brain regions in human navigation: complementary functional contributions to the formation and use of cognitive maps

The ability to orientate within familiar environments relies on the formation and use of a mental representation of the environment, namely a cognitive map. Neuropsychological and neuroimaging studies suggest that the retrosplenial and hippocampal brain regions are involved in topographical orientation. We combined functional magnetic resonance imaging with a virtual‐reality paradigm to investigate the functional interaction of the hippocampus and retrosplenial cortex during the formation and utilization of cognitive maps by human subjects. We found that the anterior hippocampus is involved during the formation of the cognitive map, while the posterior hippocampus is involved when using it. In conjunction with the hippocampus, the retrosplenial cortex was active during both the formation and the use of the cognitive map. In accordance with earlier studies in non‐human animals, these findings suggest that, while navigating within the environment, the retrosplenial cortex complements the hippocampal contribution to topographical orientation by updating the individuals location as the frame of reference changes.

Neural Substrates of Symptoms of Depression Following Concussion in Male Athletes With Persisting Postconcussion Symptoms

CONTEXT Depressed mood is frequently reported by individuals who have sustained cerebral concussion but little is known about the nature of this alteration in mood state. OBJECTIVE To investigate whether the symptoms of depression reflect an ongoing pathophysiological change following concussion. DESIGN Cohort study with male athletes using functional and structural neuroimaging. SETTING Hospital laboratory and imaging facility. PARTICIPANTS Fifty-six male athletes with and without concussion were divided into (1) a no depression symptom, concussed group, (2) a mild depression symptom, concussed group, (3) a moderate depression symptom, concussed group, and (4) a healthy control group. INTERVENTIONS All athletes filled out a postconcussive symptoms checklist and the Beck Depression Inventory II and underwent a magnetic resonance imaging session, which included T1, T2, and fluid-attenuated inversion recovery sequences, as well as functional magnetic resonance imaging (fMRI), during which they performed a working memory task. MAIN OUTCOME MEASURES (1) Behavioral: response speed and accuracy on the working memory task performed during the fMRI session; (2) functional imaging: brain activation patterns associated with the working memory task obtained using blood oxygen level-dependent fMRI; and (3) structural imaging: voxel-based morphometry examining gray matter concentration. RESULTS (1) Behavioral: there was no performance difference between the groups; and (2) imaging: athletes with concussion with depression symptoms showed reduced activation in the dorsolateral prefrontal cortex and striatum and attenuated deactivation in medial frontal and temporal regions. The severity of symptoms of depression correlated with neural responses in brain areas that are implicated in major depression. Voxel-based morphometry confirmed gray matter loss in these areas. CONCLUSIONS The results suggest that depressed mood following a concussion may reflect an underlying pathophysiology consistent with a limbic-frontal model of depression. Given that depression is associated with considerable functional disability, this finding has important clinical implications for the management of individuals with a cerebral concussion.

A validation of the post concussion symptom scale in the assessment of complex concussion using cognitive testing and functional MRI

Background: Clinical assessment of cerebral concussion relies on the presence and duration of post concussive symptoms (PCS). Given that these PCS are subjective reports and not always specific to concussion, their usefulness remains to be validated. Objective: To evaluate the usefulness of self-reported PCS by means of cognitive tests and functional MRI (fMRI). Method: 28 male athletes with and without concussion were grouped according to their PCS score. They were then administered a computerised cognitive test battery and submitted to an fMRI session where cerebral activations associated with verbal and non-verbal working memory tasks were analysed. Results: Behaviourally, response accuracy and speed on the cognitive test battery were comparable for the control and low PCS group. The moderate PCS group showed significantly slower response times than the control group on the matching (p<0.05) and one-back tasks (p<0.05). The functional MRI study showed reduced task related activation patterns in the dorsolateral prefrontal cortex for both low and moderate PCS groups. Activation peaks outside the regions of interest, not seen in the control group, were also noted for both PCS groups. Regression analyses indicated an inverse relationship between PCS scores and performances on several CogSport subtests. Severity of PCS also predicted fMRI blood oxygen level dependent signal changes in cerebral prefrontal regions. Conclusion: Self-reported PCS is associated with an ongoing cerebral haemodynamic abnormality as well as with mild cognitive impairment. These results support the use of the PCS scale in the assessment of cerebral concussion and in monitoring recovery.

New Frontiers in Diagnostic Imaging in Concussive Head Injury

Concussed athletes may have documented incapacitating postconcussive symptoms, neuropsychological deficits, and consequent important changes in their lives and sport, yet the majority of neuroimaging attempts reveal few findings to account for these signs and symptoms. In this paper, we explore new techniques in the neuroimaging of concussion including diffusion-weighted magnetic resonance imaging and functional brain imaging technology.

Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals.

We examined the effects of learning a second language (L2) on brain structure. Cortical thickness was measured in the MRI datasets of 22 monolinguals and 66 bilinguals. Some bilingual subjects had learned both languages simultaneously (0-3 years) while some had learned their L2 after achieving proficiency in their first language during either early (4-7 years) or late childhood (8-13 years). Later acquisition of L2 was associated with significantly thicker cortex in the left inferior frontal gyrus (IFG) and thinner cortex in the right IFG. These effects were seen in the group comparisons of monolinguals, simultaneous bilinguals and early and late bilinguals. Within the bilingual group, significant correlations between age of acquisition of L2 and cortical thickness were seen in the same regions: cortical thickness correlated with age of acquisition positively in the left IFG and negatively in the right IFG. Interestingly, the monolinguals and simultaneous bilinguals did not differ in cortical thickness in any region. Our results show that learning a second language after gaining proficiency in the first language modifies brain structure in an age-dependent manner whereas simultaneous acquisition of two languages has no additional effect on brain development.

Voxel-based analysis of the evolution of magnetization transfer ratio to quantify remyelination and demyelination with histopathological validation in a multiple sclerosis lesion.

We present a new method for advanced image processing to separately quantify significant decreases and increases in the magnetization transfer ratio (MTR) of individual voxels of MS lesions as markers of demyelination and remyelination. We used this method to analyze the evolution of MTR in individual voxels of an acute, Gadolinium (Gd)-enhancing lesion that was available for pathology. Over 6.5 months following enhancement, MTR was low and stable in the lesion center (81% of the initially Gd-enhancing lesion volume (GdLV)) and MTR increased at the lesion border with normal-appearing white matter (14%GdLV). The estimated error of these measurements was less than 1.8%GdLV based on scan/rescan analysis. Histopathological analysis confirmed a demyelinated lesion centre with diffuse presence of macrophages/microglia and marked loss of oligodendrocytes and a partially remyelinated lesion border with diffuse presence of macrophages/microglia and relatively more oligodendrocytes compared to the lesion centre. The correlation of imaging and histopathological findings support the validity and sensitivity of our method of voxel-based MTR image processing for monitoring demyelination and remyelination in vivo.

Recovery from mild head injury in sports: evidence from serial functional magnetic resonance imaging studies in male athletes.

Objective:To examine functional brain activation patterns before and after postconcussive symptoms (PCS) resolution. Design:Prospective serial study with male athletes using functional magnetic resonance imaging (fMRI). Setting:Hospital laboratory and imaging facility. Participants:9 symptomatic concussed athletes who experienced persisting PCS at least 1 month postinjury and 6 healthy athletes. Interventions:All athletes filled out a PCS checklist and underwent an fMRI session during which they performed a working-memory task. Main outcome measurements:Behavioral outcomes were response speed and accuracy on the working memory tasks performed during the fMRI session. Functional imaging outcomes were blood oxygen level-dependent fMRI activation patterns associated with a working memory task. Results:There was no difference in behavioral performance between the groups. Despite normal structural MRI findings, all symptomatic concussed athletes initially showed atypical brain activation patterns in the dorsolateral prefrontal cortex (DLPC). Compared to the initial postinjury evaluation, those athletes at follow-up with PCS resolved showed significant increases in activation in the left DLPC. Concussed athletes whose PCS status remained unchanged at follow-up continued to show atypical activation in DLPC. Healthy athletes showed remarkably clear and consistent brain activations in DLPC initially as well as in follow-up, highlighting the test-retest reliability of fMRI. Conclusions:The results demonstrate the feasibility of using fMRI to detect an underlying pathology in symptomatic concussed athletes with normal structural imaging results and its potential to document recovery. Such information may be of considerable value for clinical judgment and patient management.

Bilingual brain organization: A functional magnetic resonance adaptation study

We used functional magnetic resonance adaptation (fMRA) to examine whether intra-voxel functional specificity may be present for first (L1)- and second (L2)-language processing. We examined within- and across-language adaptation for spoken words in English-French bilinguals who had acquired their L2 after the age of 4 years. Subjects listened to words presented binaurally through earphones. In two control conditions (one for each language), six identical words were presented to obtain maximal adaptation. The remaining six conditions each consisted of five words that were identical followed by a sixth word that differed. There were thus a total of eight experimental conditions: no-change (sixth word identical to first five); a change in meaning (different final word in L1); a change in language (final item translated into L2); a change in meaning and language (different final word in L2). The same four conditions were presented in L2. The study also included a silent baseline. At the neural level, within- and across-language word changes resulted in release from adaptation. This was true for separate analyses of L1 and L2. We saw no evidence for greater recovery from adaptation in across-language relative to within-language conditions. While many brain regions were common to L1 and L2, we did observe differences in adaptation for forward translation (L1 to L2) as compared to backward translation (L2 to L1). The results support the idea that, at the lexical level, the neural substrates for L1 and L2 in bilinguals are shared, but with some populations of neurons within these shared regions showing language-specific responses.

Electrophysiology and Functional MRI in Post-Acute Mild Traumatic Brain Injury

Symptoms persisting beyond the acute phase (>2 months) after a mild traumatic brain injury (MTBI) are often reported, but their origin remains controversial. Some investigators evoke dysfunctional cerebral mechanisms, while others ascribe them to the psychological consequences of the injury. We address this controversy by exploring possible cerebral dysfunction with functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) in a group of patients during the post-acute phase. Fourteen MTBI symptomatic patients (5.7±2.9 months post-injury) were tested with fMRI and ERP using a visual externally ordered working memory task, and were compared with 23 control subjects. Attenuated blood oxygen level dependent (BOLD) signal changes in the left and right mid-dorsolateral prefrontal cortex (mid-DLPFC), the putamen, the body of the caudate nucleus, and the right thalamus were found in the MTBI group compared with the control group. Moreover, symptom severity and BOLD signal changes were correlated: patients with more severe symptoms had lower BOLD signal changes in the right mid-DLPFC. For ERP, a group×task interaction was observed for N350 amplitude. A larger amplitude for the working memory task than for the control task was found in control subjects, but not in MTBI subjects, who had weak amplitudes for both tasks. This study confirms that persistent symptoms after MTBI cannot be uniquely explained by psychological factors, such as depression and/or malingering, and indicates that they can be associated with cerebral dysfunction. ERP reveals decreased amplitude of the N350 component, while fMRI demonstrates that the more severe the symptoms, the lower the BOLD signal changes in the mid-DLPFC.

Local magnetization transfer ratio signal inhomogeneity is related to subsequent change in MTR in lesions and normal-appearing white-matter of multiple sclerosis patients

Multiple sclerosis (MS) lesions show differing degrees of demyelination and remyelination. Changes in myelin content are associated with changes in magnetization transfer on MRI. Since acute inflammation and demyelination are spatially and temporally inhomogeneous, we hypothesized that local magnetic transfer ratio (MTR) heterogeneity might be predictive of subsequent changes in MTR. To test this hypothesis, we analyzed MTR images obtained in 14 subjects, at baseline and after 2 months follow-up. We segmented lesions and normal-appearing white-matter (NAWM), calculated MTR signal inhomogeneity maps at baseline and MTR lesion difference maps between baseline and follow-up. We found that regions with low MTR inhomogeneity at baseline experienced little further change in MTR on follow-up. The mean change in lesion MTR between baseline and follow-up was 0.10 +/- 3.70; in NAWM it was -0.09 +/- 2.02. We found that regions with high MTR inhomogeneity at baseline would change MTR on follow-up: (1) voxels with significantly high MTR in regions of high MTR inhomogeneity at baseline showed a mean decrease in MTR between baseline and follow-up of -2.51 +/- 4.68 in lesions and -1.41 +/- 3.00 in NAWM; (2) voxels with low MTR in regions of high MTR inhomogeneity at baseline showed a mean increase in MTR between baseline and follow-up of 2.61 +/- 6.07 in lesions. These changes in MTR were significantly different (P < 0.001). These results suggest that calculation of MTR signal inhomogeneity may provide a method for quantifying the potential for remyelination and demyelination, and thus could provide an important MRI biomarker for assessing the efficacy of therapies targeting remyelination.