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.

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.

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.

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.

Effects of language and acculturation on neurocognitive performance of Japanese Americans.

OBJECTIVE: Despite significant work in African and Hispanic American populations, little information is available regarding performance of Japanese Americans on neuropsychological tests. The aim of this study was to examine the effects of dominant language and acculturation levels on the performance of Japanese Americans on selected neurocognitive tests. METHOD: Based on their self-identified dominant language, 48 English-dominant speaking (ES) Japanese Americans (Mage = 64.48, SD = 10.52) and 52 Japanese-dominant speaking (JS) Japanese Americans (Mage = 60.17, SD = 11.15) were assessed on a neurocognitive battery. RESULTS: Significant differences in test performance were observed between the groups, with the JS group performing poorer on the measures of naming ability, verbal and olfactory learning/memory, and language, compared to the ES group. Levels of acculturation explained that group difference. The Brief Visuospatial Memory Test-Revised (BVMT-R) showed no group differences, suggesting lack of language proficiency and acculturation biases in this ethnic sample. Within the JS group, self-reported English proficiency and years of education obtained in Japan explained variance in addition to age, education, and gender, in performance on the Boston Naming Test and the Letter Fluency Test, respectively. CONCLUSIONS: The present study highlights the need for culturally sensitive evaluation in the neuropsychological assessment of this population. The variability in backgrounds contributed to the variability in performance between and within groups. Factors in addition to age and education, including the effects of primary language and acculturation, warrant consideration when evaluating the neuropsychological performance of Japanese Americans in research and clinical settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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. METHODS: We performed diffusion tensor imaging tractography and cortical thickness analyses of 18 patients with left TLE (LTLE), 18 patients with right TLE (RTLE), and 36 controls. We investigated the relationship among brain structural abnormalities, side of seizure onset, age of seizure onset, and disease duration. KEY FINDINGS: Patients with TLE displayed cortical thinning and white matter compromise, predominately on the side ipsilateral to the seizure onset. Relative to RTLE, patients with LTLE showed more widespread abnormalities, particularly in white matter fiber tracts. Greater compromise in white matter integrity was associated with earlier age of seizure onset, whereas cortical thinning was marginally associated with disease duration. SIGNIFICANCE: These data support previous findings of LTLE showing greater structural compromise than RTLE, and suggest that mechanisms may not be uniform for gray and white matter compromise in patients with LTLE and RTLE. These results may indicate that LTLE is different from RTLE, possibly due to greater vulnerability of the left hemisphere to early injury and the progressive effects of seizures.

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.

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.

Restrained eaters show altered brain response to food odor.

Do restrained and unrestrained eaters differ in their brain response to food odor? We addressed this question by examining restrained eaters' brain response to food (chocolate) and non-food (geraniol, floral) odors, both when odor was attended to and when ignored. Using olfactory event-related potentials (OERPs), we found that restrained eaters and controls responded similarly to the non-food odor; however, unlike controls, restrained eaters showed no increase in brain response to the food odor when they focused attention on it. Rather, restrained eaters showed attenuated OERP amplitudes to the food odor in both attended and ignored conditions, suggesting that the brain's response to attended food odor was abnormally suppressed.

Activity and functional connectivity of inferior frontal cortex associated with response conflict.

The traditional Stroop test of cognitive interference requires overt speech responses. One alternative, the counting Stroop, generates cognitive interference similar to the traditional Stroop test but allows button press responses. Previous counting Stroop studies have used concrete words in the control condition, which may have masked inferior frontal activation. We studied 7 healthy young adults using fMRI on a counting Stroop condition, with a nonlinguistic control condition (geometric shapes). As expected, we found activation in bilateral inferior frontal gyri, as well as in lateral and medial prefrontal, inferior parietal, and extrastriate cortices. Additional functional connectivity analyses using inferior frontal activation clusters (right area 44, left area 47) as seed volumes showed connectivity with superior frontal area 8 and anterior cingulate gyrus, suggesting that the role of inferior frontal cortex was related to response conflict and inhibition. Connectivity with left perisylvian language areas was not observed, which further underscores the nonlinguistic nature of inferior frontal activity. We conclude that bilateral inferior frontal cortex is involved in response suppression associated with interference in the counting Stroop task.

Abnormal variability and distribution of functional maps in autism: an FMRI study of visuomotor learning.

OBJECTIVE: Autism is a neurally based psychiatric disorder, but there is no consensus regarding the underlying neurofunctional abnormalities. Previous functional magnetic resonance imaging (fMRI) studies of simple movement suggested individually variable and scattered functional brain organization in autism. The authors examined whether such abnormalities generalize to multimodal processing (visually driven motor sequence learning). METHOD: Eight male autistic patients and eight comparison subjects matched with the patients on age, gender, and handedness were examined by using fMRI while they performed finger press movements prompted by visually presented repeating six-digit sequences. Hemodynamic responses to the six-digit sequences were statistically compared to responses to single-digit stimuli in one experiment and to regular six-digit sequences in another experiment. RESULTS: Both groups showed activations in bilateral premotor, superior parietal, and occipital cortices in both experiments. Task-by-group interactions showed that superior parietal activations were less pronounced in the autism group, whereas prefrontal cortex and more posterior parietal loci showed greater activation in the autism group than in the comparison group. The distances between Individual subjects' activation peaks and the groupwise peak were greater in the autism group than in the comparison group. CONCLUSIONS: The results support earlier findings of abnormal variability and scatter of functional maps in autism. They are consistent with evidence from other studies suggesting early-onset disturbances in the development of cerebello-thalamo-cortical pathways in autism.

Functional MRI of motor sequence acquisition: effects of learning stage and performance.

Neural networks of motor control are well understood and the motor domain therefore lends itself to the study of learning. Neuroimaging of motor learning has demonstrated fronto-parietal, subcortical, and cerebellar involvement. However, there is conflicting evidence on the specific functional contributions of individual regions and their relative importance for early and advanced stages of learning. Using functional MRI (fMRI), we examined hemodynamic effects in seven right-handed men during brief episodes of explicit learning of novel six-digit sequences (experiments 1 and 2) and during prolonged learning of an eight-digit sequence (experiment 3), all performed with the dominant hand. Brief episodes of new learning were predominantly associated with bilateral activations in premotor and supplementary motor areas, superior and inferior parietal cortices, and anterior cerebellum. In experiment 2, which included a control condition matched for complexity of motor execution, we also found unexpectedly strong activation in the bilateral inferior frontal lobes. In experiment 3, analysis of task by learning stage interactions showed greater involvement of the bilateral superior parietal lobes, the right middle frontal gyrus, and the left caudate nucleus during early stages, whereas left occipito-temporal and superior frontal cortex as well as the bilateral parahippocampal region were more activated during late learning stages. Analysis of task by performance interactions (based on each subject's response times and accuracy during each scan) showed effects in bilateral fronto-polar, right hippocampal, and anterior cerebellar regions associated with high levels of performance, as well as inverse effects in bilateral occipito-parietal regions. We conclude that superior parietal and occipital regions are most intensely involved in visually driven explicit digit sequence learning during early stages and low performance, whereas later stages of acquisition and higher levels of performance are characterized by stronger recruitment of prefrontal and mediotemporal regions.

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.

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.

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.

Pre- and post- GPi DBS neuropsychological profiles in a case of X-linked dystonia-Parkinsonism.

We present the pre to post bilateral globus pallidus interna (GPi) deep brain stimulation neuropsychological profiles of a 69-year-old patient with a 12-year history of X-linked dystonia-Parkinsonism (XDP). Pre-operative cognitive function was impaired in almost all domains and this impaired performance was not dependent on his medications. Following DBS, changes in neuropsychological functioning were examined using Reliable Change Indices and standardized z-score comparisons. Results showed reductions in processing speed in the context of stable performance in language and visuospatial domains. Post-operative improvements occurred on a cognitive screening measure, verbal memory, and a test of problem-solving skills. This is the first report on an individual with XDP who was cognitively impaired, but had good outcome following GPi bilateral stimulation to treat debilitating motor symptoms. The possible mechanisms for his stable cognitive performance include the target of his DBS, reduced medication dosage, and improvement in dystonia that may in turn have reduced patient's pain.

Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism.

Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and eight handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional.