Nobuko Kemmotsu

MRI analysis in temporal lobe epilepsy: Cortical thinning and white matter disruptions are related to side of seizure onset

Purpose:  Past studies reported more widespread structural brain abnormalities in patients with left compared to right temporal lobe epilepsy (TLE), but the profile of these differences remains unknown. This study investigated the relationship between cortical thinning, white matter compromise, epilepsy variables, and the side of seizure onset, in patients with TLE.

Temporal Lobe Epilepsy: Quantitative MR Volumetry in Detection of Hippocampal Atrophy

PURPOSE To determine the ability of fully automated volumetric magnetic resonance (MR) imaging to depict hippocampal atrophy (HA) and to help correctly lateralize the seizure focus in patients with temporal lobe epilepsy (TLE). MATERIALS AND METHODS This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Volumetric MR imaging data were analyzed for 34 patients with TLE and 116 control subjects. Structural volumes were calculated by using U.S. Food and Drug Administration-cleared software for automated quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR imaging were compared with visual detection of atrophy, and, when available, with histologic specimens. Receiver operating characteristic analyses were performed to determine the optimal sensitivity and specificity of quantitative MR imaging for detecting HA and asymmetry. A linear classifier with cross validation was used to estimate the ability of quantitative MR imaging to help lateralize the seizure focus. RESULTS Quantitative MR imaging-derived hippocampal asymmetries discriminated patients with TLE from control subjects with high sensitivity (86.7%-89.5%) and specificity (92.2%-94.1%). When a linear classifier was used to discriminate left versus right TLE, hippocampal asymmetry achieved 94% classification accuracy. Volumetric asymmetries of other subcortical structures did not improve classification. Compared with invasive video electroencephalographic recordings, lateralization accuracy was 88% with quantitative MR imaging and 85% with visual inspection of volumetric MR imaging studies but only 76% with visual inspection of clinical MR imaging studies. CONCLUSION Quantitative MR imaging can depict the presence and laterality of HA in TLE with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Thus, quantitative MR imaging may enhance standard visual analysis, providing a useful and viable means for translating volumetric analysis into clinical practice.

White matter microstructure complements morphometry for predicting verbal memory in epilepsy.

Verbal memory is the most commonly impaired cognitive domain in patients with temporal lobe epilepsy (TLE). Although damage to the hippocampus and adjacent temporal lobe structures is known to contribute to memory impairment, little is known of the relative contributions of white versus gray matter structures, or whether microstructural versus morphometric measures of temporal lobe pathology are stronger predictors of impairment. We evaluate whether measures of temporal lobe pathology derived from diffusion tensor imaging (DTI; microstructural) versus structural MRI (sMRI; morphometric) contribute the most to memory performances in TLE, after controlling for hippocampal volume (HCV). DTI and sMRI were performed on 26 patients with TLE and 35 controls. Verbal memory was measured with the Logical Memory (LM) subtest of the Wechsler Memory Scale-III. Hierarchical regression analyses were performed to examine unique contributions of DTI and sMRI measures to verbal memory with HCV entered in block 1. In patients, impaired recall was associated with increased mean diffusivity (MD) of multiple fiber tracts that project through the temporal lobes. In addition, increased MD of the left cortical and bilateral pericortical white matter was associated with impaired recall. After controlling for left HCV, only microstructural measures of white matter pathology contributed to verbal recall. The best predictive model included left HCV and MD of the left inferior longitudinal fasciculus (ILF) and pericortical white matter beneath the left entorhinal cortex. This model explained 60% of the variance in delayed recall and revealed that MD of the left ILF was the strongest predictor. These data reveal that white matter microstructure within the temporal lobe can be used in conjunction with left HCV to enhance the prediction of verbal memory impairment, and speak to the complementary nature of DTI and sMRI for understanding cognitive dysfunction in epilepsy and possibly other memory disorders.

Frontolimbic Brain Networks Predict Depressive Symptoms in Temporal Lobe Epilepsy

Psychiatric co-morbidities in epilepsy are of great concern. The current study investigated the relative contribution of structural and functional connectivity (FC) between medial temporal (MT) and prefrontal regions in predicting levels of depressive symptoms in patients with temporal lobe epilepsy (TLE). Twenty-one patients with TLE [11 left TLE (LTLE); 10 right TLE (RTLE)] and 20 controls participated. Diffusion tensor imaging was performed to obtain fractional anisotropy (FA) of the uncinate fasciculus (UF), and mean diffusivity (MD) of the amygdala (AM) and hippocampus (HC). Functional MRI was performed to obtain FC strengths between the AM and HC and prefrontal regions of interest including anterior prefrontal (APF), orbitofrontal, and inferior frontal regions. Participants self-reported depression symptoms on the Beck Depression Inventory-II. Greater depressive symptoms were associated with stronger FC of ipsilateral HC-APF, lower FA of the bilateral UF, and higher MD of the ipsilateral HC in LTLE, and with lower FA of the contralateral UF in RTLE. Regression analyses indicated that FC of the ipsilateral HC-APF was the strongest contributor to depression in LTLE, explaining 68.7% of the variance in depression scores. Both functional and microstructural measures of frontolimbic dysfunction were associated with depressive symptoms. These connectivity variables may be moderating which patients present with depression symptoms. In particular, FC MRI may provide a more sensitive measure of depression-related dysfunction, at least in patients with LTLE. Employing sensitive measures of frontolimbic network dysfunction in TLE may help provide new insight into mood disorders in epilepsy that could eventually guide treatment planning.

Alterations in functional connectivity between the hippocampus and prefrontal cortex as a correlate of depressive symptoms in temporal lobe epilepsy

Depression is a common comorbidity in temporal lobe epilepsy (TLE) that is thought to have a neurobiological basis. This study investigated the functional connectivity (FC) of medial temporal networks in depression symptomatology of TLE and the relative contribution of structural versus FC measures. Volumetric MRI and functional connectivity MRI (fcMRI) were performed on nineteen patients with TLE and 20 controls. The hippocampi and amygdalae were selected as seeds, and five prefrontal and five cingulate regions of interest (ROIs) were selected as targets. Low-frequency blood-oxygen-level-dependent signals were isolated from fcMRI data, and ROIs with synchronous signal fluctuations with the seeds were identified. Depressive symptoms were measured by the Beck Depression Inventory-II. The patients with TLE showed greater ipsilateral hippocampal atrophy (HA) and reduced FC between the ipsilateral hippocampus and the ventral posterior cingulate cortex (vPCC). Neither HA nor hippocampal-vPCC FC asymmetry was a robust contributor to depressive symptoms. Rather, hippocampal-anterior prefrontal FC was a stronger contributor to depressive symptoms in left TLE (LTLE). Conversely, right amygdala FC was correlated with depressive symptoms in both patient groups, with a positive and negative correlation in LTLE and right TLE (RTLE), respectively. Frontolimbic network dysfunction is a strong contributor to levels of depressive symptoms in TLE and a better contributor than HA in LTLE. In addition, the right amygdala may play a role in depression symptomatology regardless of the side of the epileptogenic focus. These findings may inform the treatment of depressive symptoms in TLE and inspire future research to help guide surgical planning.

Functional Connectivity of the Hippocampus in Temporal Lobe Epilepsy: Feasibility of a Task-Regressed Seed-Based Approach

OBJECTIVE Resting-state functional connectivity (FC) has revealed marked network dysfunction in patients with temporal lobe epilepsy (TLE) compared to healthy controls. However, the nature and the location of these changes have not been fully elucidated nor confirmed by other methodologies. We assessed the presence of hippocampal FC changes in TLE based on the low frequency residuals of task-related functional magnetic resonance imaging data after the removal of task-related activation [i.e., task-regressed functional connectivity MRI (fcMRI)]. METHOD We employed a novel, task-regressed approach to quantify hippocampal FC, and compare hippocampal FC in 17 patients with unilateral TLE (9 left) with 17 healthy controls. RESULTS Our results suggest widespread FC reductions in the mesial cortex associated with the default mode network (DMN), and some local FC increases in the lateral portions of the right hemisphere. We found more pronounced FC decreases in the left hemisphere than in the right, and these FC decreases were greatest in patients with left TLE. Moreover, the FC reductions observed between the hippocampus and posterior cingulate, inferior parietal, paracentral regions are in agreement with previous resting state studies. CONCLUSIONS Consistent with the existing literature, FC reductions in TLE appear widespread with prominent reductions in the medial portion of the DMN. Our data expand the literature by demonstrating that reductions in FC may be greatest in the left hemisphere and in patients with left TLE. Overall, our findings suggest that task-regressed FC is a viable alternative to resting state and that future studies may extract similar information on network connectivity from already existing datasets.

Age-related changes in the neurophysiology of language in adults: Relationship to regional cortical thinning and white matter microstructure

Although reading skill remains relatively stable with advancing age in humans, neurophysiological measures suggest potential reductions in efficiency of lexical information processing. It is unclear whether these age-related changes are secondary to decreases in regional cortical thickness and/or microstructure of fiber tracts essential to language. Magnetoencephalography, volumetric MRI, and diffusion tensor imaging were performed in 10 young (18–33 years) and 10 middle-aged (42–64 years) human individuals to evaluate the spatiotemporal dynamics and structural correlates of age-related changes in lexical-semantic processing. Increasing age was associated with reduced activity in left temporal lobe regions from 250 to 350 ms and in left inferior prefrontal cortex from 350 to 450 ms (i.e., N400). Hierarchical regression indicated that age no longer predicted left inferior prefrontal activity after cortical thickness and fractional anisotropy (FA) of the uncinate fasciculus (UF) were considered. Interestingly, FA of the UF was a stronger predictor of the N400 response than cortical thickness. Age-related reductions in left-lateralization of language responses were observed between 250 and 350 ms, and were associated with left temporal thinning and frontotemporal FA reductions. N400 reductions were not associated with poorer task performance. Rather, increasing age was associated with reduction in the left prefrontal N400, which in turn was also associated with slower response time. These results reveal that changes in the neurophysiology of language occur by middle age and appear to be partially mediated by structural brain loss. These neurophysiological changes may reflect an adaptive process that ensues as communication between left perisylvian regions declines.

Does medial temporal lobe thickness mediate the association between risk factor burden and memory performance in middle-aged or older adults with metabolic syndrome?

Metabolic syndrome (MetS) is a cluster of cardiovascular and metabolic abnormalities that together may increase the risk of developing cognitive decline and dementia; however, the neural substrate is incompletely understood. We investigated cortical thickness in the medial temporal lobe (MTL), hippocampal volume, as well as relationships among metabolic risk factor burden, structure and memory performance. Path-analytic models were tested to explore the relations between MetS risk factor, structure and memory performance. Participants were 65 non-demented, middle-aged and older adults, 34 with and 31 without metabolic syndrome. We analyzed archival T1-weighted magnetic resonance imaging (MRI) acquired at 3T and Total Recall and Delayed Recall scores from the Brief Visuospatial Memory Test Revised (BVMT-R). Middle-aged adults with MetS showed less MTL thickness, particularly in entorhinal cortex; while older adults showed a trend for left hippocampal volume loss. Lower MTL thickness, particularly in entorhinal cortex, was associated with greater metabolic risk factor burden in middle-aged adults. In older adults, hippocampal volume was associated with Total Recall and Delayed Recall, while in middle-age entorhinal cortical thickness mediated the association between metabolic disease burden and episodic memory function. The differential findings in middle-aged and older adults with MetS contribute to an understanding of the relationships between metabolic syndrome, structural changes in the brain and increased risk for cognitive decline.

Multimodal imaging of language reorganization in patients with left temporal lobe epilepsy

HighlightsMultimodal imaging can help to localize language networks in LTLE.Interhemispheric language reorganization is associated with alternations to the ARC.Structural and functional shifts mitigate language impairment in LTLE. ABSTRACT This study explored the relationships among multimodal imaging, clinical features, and language impairment in patients with left temporal lobe epilepsy (LTLE). Fourteen patients with LTLE and 26 controls underwent structural MRI, functional MRI, diffusion tensor imaging, and neuropsychological language tasks. Laterality indices were calculated for each imaging modality and a principal component (PC) was derived from language measures. Correlations were performed among imaging measures, as well as to the language PC. In controls, better language performance was associated with stronger left‐lateralized temporo‐parietal and temporo‐occipital activations. In LTLE, better language performance was associated with stronger right‐lateralized inferior frontal, temporo‐parietal, and temporo‐occipital activations. These right‐lateralized activations in LTLE were associated with right‐lateralized arcuate fasciculus fractional anisotropy. These data suggest that interhemispheric language reorganization in LTLE is associated with alterations to perisylvian white matter. These concurrent structural and functional shifts from left to right may help to mitigate language impairment in LTLE.

Performance of Older Japanese American Adults on Selected Cognitive Instruments

This study examined cognitive test performance of second- and third-generation Japanese American (JA) adults, a relatively homogeneous Asian American subgroup. Sixty-five JA and 65 non-Hispanic White (NHW) adults, ages between 45 and 91, were administered the Boston Naming Test-2 (BNT), Letter Fluency Test, Semantic Fluency Test, California Verbal Learning Test (CVLT), Brief Visuospatial Memory Test-Revised (BVMT-R), and Trail Making Test. Levels of acculturation, quality of educational attainment, and generation status in the United States, were also collected. There were no significant differences in the scores between the two groups on the tests administered. JA and NHW groups, however, differed in the patterns of the associations between some of the test performance and demographic variables. JA adults showed a stronger age-score relationship on BNT, CVLT, and the BVMT-R. Furthermore, second-generation JA adults performed lower than the third-generation adults even after controlling for basic demographic variables on CVLT and Trail Making Test. Acculturation on the other hand did not explain score differences once demographic variables were considered. Our results suggest the importance of considering unique history and characteristics of ethnic groups, and interactions of the aging process and culture on tasks with different cognitive demands.