Leveraging expertise and optimizing clinical research: Initial success of a pediatric epilepsy surgery collaborative.

OBJECTIVE: Improve data-driven research to inform clinical decision-making with pediatric epilepsy surgery patients by expanding the Pediatric Epilepsy Research Consortium Epilepsy Surgery (PERC-Surgery) Workgroup to include neuropsychological data. This article reports on the process and initial success of this effort and characterizes the cognitive functioning of the largest multi-site pediatric epilepsy surgery cohort in the United States. METHODS: Pediatric neuropsychologists from 18 institutions completed surveys regarding neuropsychological practice and the impact of involvement in the collaborative. Neuropsychological data were entered through an online database. Descriptive analyses examined the survey responses and cognitive functioning of the cohort. Statistical analyses examined which patients were evaluated and if composite scores differed by domain, demographics, measures used, or epilepsy characteristics. RESULTS: Positive impact of participation was evident by attendance, survey responses, and the neuropsychological data entry of 534 presurgical epilepsy patients. This cohort, ages 6 months to 21 years, were majority White and non-Hispanic, and more likely to have private insurance. Mean intelligence quotient (IQ) scores were below to low average, with weaknesses in working memory and processing speed. Full-scale IQ (FSIQ) was lowest for patients with younger age at seizure onset, daily seizures, and magnetic resonance imaging (MRI) abnormalities. SIGNIFICANCE: We established a collaborative network and fundamental infrastructure to address questions outlined by the Epilepsy Research Benchmarks. There is a wide range in the age and IQ of patients considered for pediatric epilepsy surgery, yet it appears that social determinants of health impact access to care. Consistent with other national cohorts, this US cohort has a downward shift in IQ associated with seizure severity.

Impaired Behavioral Pattern Separation in Refractory Temporal Lobe Epilepsy and Mild Cognitive Impairment.

OBJECTIVE: Episodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI. METHOD: Patients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST). Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test-Second Edition scores, and MST performance were tested in the TLE group. RESULTS: Patients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance. CONCLUSION: Memory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.

The impact of cerebrovascular risk factors on postoperative memory decline in patients with left temporal lobe epilepsy.

Cerebrovascular risk factors (CVRFs) and comorbid cardiovascular and metabolic disease have been linked to accelerated cognitive aging and dementia in the general population; however, the contribution of these comorbidities to the risk of post anterior temporal lobectomy (ATL) memory decline has been unexamined. We explored the effects of CVRFs on postoperative verbal memory decline in a cohort of 22 patients with left temporal lobe epilepsy (LTLE) who completed pre- and one-year postsurgical neuropsychological testing. Diagnoses of interest included preoperative cardiovascular and metabolic disorders, as well as CVRFs [pulse pressure proxy, body mass index (BMI), and fasting glucose]. Twenty-three percent of patients had a history of cardiovascular disease, 9% of metabolic disorders, and 38% had a BMI indicating overweight or obese status. Higher preoperative BMI and glucose were associated with greater decline in verbal memory. The association between BMI and memory decline remained significant after controlling for age and left hippocampal volume. These findings suggest that modifiable health-related risk factors, including CVRFs, may impact the risk of postoperative cognitive decline, and that BMI in particular could be an important factor to consider and/or target for intervention early in clinical care to protect cognitive health.

Identifying the neural basis of a language-impaired phenotype of temporal lobe epilepsy.

OBJECTIVE: To identify neuroimaging and clinical biomarkers associated with a language-impaired phenotype in refractory temporal lobe epilepsy (TLE). METHODS: Eighty-five patients with TLE were characterized as language-impaired (TLE-LI) or non-language-impaired (TLE-NLI) based on comprehensive neuropsychological testing. Structural magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) were obtained in patients and 47 healthy controls (HC). fMRI activations and cortical thickness were calculated within language regions of interest, and fractional anisotropy (FA) was calculated within deep white matter tracts associated with language. Analyses of variance were performed to test for differences among the groups in imaging measures. Receiver operator characteristic curves were used to determine how well different clinical versus imaging measures discriminated TLE-LI from TLE-NLI. RESULTS: TLE-LI patients showed significantly less activation within left superior temporal cortex compared to HC and TLE-NLI, regardless of side of seizure onset. TLE-LI also showed decreased FA in the inferior longitudinal fasciculus and arcuate fasciculus compared to HC. Cortical thickness did not differ between groups in any region. A model that included language-related fMRI activations within the superior temporal gyrus, age at onset, and demographic variables was the most predictive of language impairment (area under the curve = 0.80). SIGNIFICANCE: These findings demonstrate a unique imaging signature associated with a language-impaired phenotype in TLE, characterized by functional and microstructural alterations within the language network. Reduced left superior temporal activation combined with compromise to language association tracts underlies this phenotype, extending our previous work on cognitive phenotypes that could have implications for treatment-planning or cognitive progression in TLE.

Differential sensitivity of structural, diffusion, and resting-state functional MRI for detecting brain alterations and verbal memory impairment in temporal lobe epilepsy.

OBJECTIVES: Temporal lobe epilepsy (TLE) is known to affect large-scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment. METHODS: Diffusion tensor imaging (DTI), volumetric magnetic resonance imaging (vMRI), and resting-state functional MRI (rs-fMRI) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [SWM]) for DTI and across neocortex for vMRI and rs-fMRI. The degree to which imaging alterations within left medial temporal lobe/posterior cingulate (LMT/PC) and left lateral temporal regions were associated with verbal memory performance was evaluated. RESULTS: Patients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [FA] and increased mean diffusivity [MD]) spanning the entire frontal and temporolimbic SWM, which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs-fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT/PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume. SIGNIFICANCE: These findings suggest that microstructural loss within the SWM is pronounced in patients with TLE, and injury to the SWM within the LMT/PC region plays a critical role in verbal memory impairment.

Does bilingualism increase brain or cognitive reserve in patients with temporal lobe epilepsy?

OBJECTIVE: Bilingual healthy adults have been shown to exhibit an advantage in executive functioning (EF) that is associated with microstructural changes in white matter (WM) networks. Patients with temporal lobe epilepsy (TLE) often show EF deficits that are associated with WM compromise. In this study, we investigate whether bilingualism can increase cognitive reserve and/or brain reserve in bilingual patients with TLE, mitigating EF impairment and WM compromise. METHODS: Diffusion tensor imaging was obtained in 19 bilingual and 26 monolingual patients with TLE, 12 bilingual healthy controls (HC), and 21 monolingual HC. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for the uncinate fasciculus (Unc) and cingulum (Cing), superior frontostriatal tract (SFS), and inferior frontostriatal tract (IFS). Measures of EF included Trail Making Test-B (TMT-B) and Delis-Kaplan Executive Function System Color-Word Inhibition/Switching. Analyses of covariance were conducted to compare FA and MD of the Unc, Cing, SFS, and IFS and EF performance across groups. RESULTS: In bilingual patients, FA was lower in the ipsilateral Cing and Unc compared to all other groups. For both patient groups, MD of the ipsilateral Unc was higher relative to HC. Despite more pronounced reductions in WM integrity, bilingual patients performed similarly to monolingual TLE and both HC groups on EF measures. By contrast, monolingual patients performed worse than HC on TMT-B. In addition, differences in group means between bilingual and monolingual patients on TMT-B approached significance when controlling for the extent of WM damage (P = .071; d = 0.62), suggesting a tendency toward higher performance for bilingual patients. SIGNIFICANCE: Despite poorer integrity of regional frontal lobe WM, bilingual patients performed similarly to monolingual patients and HC on EF measures. These findings align with studies suggesting that bilingualism may provide a protective factor for individuals with neurological disease, potentially through reorganization of EF networks that promote greater cognitive reserve.

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy.

OBJECTIVE: Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI's ability to separate intraaxonal diffusion (i.e., neurite density; ND) from diffusion associated with extraaxonal factors (e.g., inflammation; crossing fibers). METHODS: RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic-hindered (IH) and isotropic-free (IF) water, and crossing fibers (CFs) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. RESULTS: Reductions in FA were seen primarily in frontotemporal white matter in TLE, and they were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. SIGNIFICANCE: RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy.

The importance of basal-temporal white matter to pre- and post-surgical naming ability in temporal lobe epilepsy.

OBJECTIVE: Emerging research highlights the importance of basal-temporal cortex, centered on the fusiform gyrus, to both pre-surgical naming ability and post-surgical naming outcomes in temporal lobe epilepsy (TLE). In this study, we investigate whether integrity of the white matter network that interconnects this basal region to the distributed language network affects naming ability and risk for post-surgical naming decline. METHODS: Patients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-surgical dataset included 50 healthy controls, 47 left TLE (L-TLE), and 41 right TLE (R-TLE) patients. All participants completed pre-surgical T1- and diffusion-weighted MRI (dMRI), as well as neuropsychological tests of auditory and visual naming. Nineteen L-TLE and 18 R-TLE patients underwent anterior temporal lobectomy (ATL) and also completed post-surgical neuropsychological testing. Pre-surgical fractional anisotropy (FA) of the white matter directly beneath the fusiform neocortex (i.e., superficial white matter; SWM) and of deep white matter tracts with connections to the basal-temporal cortex [inferior longitudinal fasciculus (ILF) and inferior frontal occipital fasciculus (IFOF)] was calculated. Clinical variables, hippocampal volume, and FA of each white matter tract or region were examined in linear regressions with naming scores, or change in naming scores, as the primary outcomes. RESULTS: Pre-surgically, higher FA in the bilateral ILF, bilateral IFOF, and left fusiform SWM was associated with better visual and auditory naming scores (all ps < 0.05 with FDR correction). In L-TLE, higher pre-surgical FA was also associated with less naming decline post-surgically, but results varied across tracts. When including only patients with typical language dominance, only integrity of the right fusiform SWM was associated with less visual naming decline (p = .0018). DISCUSSION: Although a broad network of white matter network matter may contribute to naming ability pre-surgically, the reserve capacity of the contralateral (right) fusiform SWM may be important for mitigating visual naming decline following ATL in L-TLE. This shows that the study of the structural network interconnecting the basal-temporal region to the wider language network has implications for understanding both pre- and post-surgical naming in TLE.

The white matter connectome as an individualized biomarker of language impairment in temporal lobe epilepsy.

OBJECTIVE: The distributed white matter network underlying language leads to difficulties in extracting clinically meaningful summaries of neural alterations leading to language impairment. Here we determine the predictive ability of the structural connectome (SC), compared with global measures of white matter tract microstructure and clinical data, to discriminate language impaired patients with temporal lobe epilepsy (TLE) from TLE patients without language impairment. METHODS: T1- and diffusion-MRI, clinical variables (CVs), and neuropsychological measures of naming and verbal fluency were available for 82 TLE patients. Prediction of language impairment was performed using a robust tree-based classifier (XGBoost) for three models: (1) a CV-model which included demographic and epilepsy-related clinical features, (2) an atlas-based tract-model, including four frontotemporal white matter association tracts implicated in language (i.e., the bilateral arcuate fasciculus, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus), and (3) a SC-model based on diffusion MRI. For the association tracts, mean fractional anisotropy was calculated as a measure of white matter microstructure for each tract using a diffusion tensor atlas (i.e., AtlasTrack). The SC-model used measurement of cortical-cortical connections arising from a temporal lobe subnetwork derived using probabilistic tractography. Dimensionality reduction of the SC was performed with principal components analysis (PCA). Each model was trained on 49 patients from one epilepsy center and tested on 33 patients from a different center (i.e., an independent dataset). Randomization was performed to test the stability of the results. RESULTS: The SC-model yielded a greater area under the curve (AUC; .73) and accuracy (79%) compared to both the tract-model (AUC: .54, p < .001; accuracy: 70%, p < .001) and the CV-model (AUC: .59, p < .001; accuracy: 64%, p < .001). Within the SC-model, lateral temporal connections had the highest importance to model performance, including connections similar to language association tracts such as links between the superior temporal gyrus to pars opercularis. However, in addition to these connections many additional connections that were widely distributed, bilateral and interhemispheric in nature were identified as contributing to SC-model performance. CONCLUSION: The SC revealed a white matter network contributing to language impairment that was widely distributed, bilateral, and lateral temporal in nature. The distributed network underlying language may be why the SC-model has an advantage in identifying sub-components of the complex fiber networks most relevant for aspects of language performance.

Clinical utility of structural connectomics in predicting memory in temporal lobe epilepsy.

OBJECTIVE: To determine the predictive power of white matter neuronal networks (i.e., structural connectomes [SCs]) in discriminating memory-impaired patients with temporal lobe epilepsy (TLE) from those with normal memory. METHODS: T1- and diffusion MRI (dMRI), clinical variables, and neuropsychological measures of verbal memory were available for 81 patients with TLE. Prediction of memory impairment was performed with a tree-based classifier (XGBoost) for 4 models: (1) a clinical model including demographic and clinical features, (2) a hippocampal volume (HCV) model, (3) a tract model including 5 temporal lobe white matter association tracts derived from a dMRI atlas, and (4) an SC model based on dMRI. SCs were derived by extracting cortical-cortical connections from a temporal lobe subnetwork with probabilistic tractography. Principal component (PC) analysis was then applied to reduce the dimensionality of the SC, yielding 10 PCs. Multimodal models were also tested combining SCs and tracts with HCV. Each model was trained on 48 patients from 1 epilepsy center and tested on 33 patients from a different center. RESULTS: Multimodal models that included the SC + HCV model yielded the highest classification accuracy (81%; 0.90 sensitivity; 0.67 specificity), outperforming the clinical model (61%; p < 0.001) and HCV model (66%; p < 0.001). In addition, the unimodal SC model (76% accuracy) and tract model (73% accuracy) outperformed the clinical model (p < 0.001) and HCV model (p < 0.001) for classifying patients with TLE with and without memory impairment. Furthermore, the SC identified that short-range temporal-temporal connections were important contributors to memory performance. CONCLUSION: SCs and tract-based models are stronger predictors of memory impairment in TLE than HCVs and clinical variables. However, SCs may provide additional information about local cortical-cortical connectivity contributing to memory that is not captured in large association tracts.

Cognitive phenotypes in temporal lobe epilepsy are associated with distinct patterns of white matter network abnormalities.

OBJECTIVE: To identify distinct cognitive phenotypes in temporal lobe epilepsy (TLE) and evaluate patterns of white matter (WM) network alterations associated with each phenotype. METHODS: Seventy patients with TLE were characterized into 4 distinct cognitive phenotypes based on patterns of impairment in language and verbal memory measures (language and memory impaired, memory impaired only, language impaired only, no impairment). Diffusion tensor imaging was obtained in all patients and in 46 healthy controls (HC). Fractional anisotropy (FA) and mean diffusivity (MD) of the WM directly beneath neocortex (i.e., superficial WM [SWM]) and of deep WM tracts associated with memory and language were calculated for each phenotype. Regional and network-based SWM analyses were performed across phenotypes. RESULTS: The language and memory impaired group and the memory impaired group showed distinct patterns of microstructural abnormalities in SWM relative to HC. In addition, the language and memory impaired group showed widespread alterations in WM tracts and altered global SWM network topology. Patients with isolated language impairment exhibited poor network structure within perisylvian cortex, despite relatively intact global SWM network structure, whereas patients with no impairment appeared similar to HC across all measures. CONCLUSIONS: These findings demonstrate a differential pattern of WM microstructural abnormalities across distinct cognitive phenotypes in TLE that can be appreciated at both the regional and network levels. These findings not only help to unravel the underlying neurobiology associated with cognitive impairment in TLE, but they could also aid in establishing cognitive taxonomies or in the prediction of cognitive course in TLE.

Beyond depression: The impact of executive functioning on quality of life in patients with temporal lobe epilepsy.

OBJECTIVE: Individuals with temporal lobe epilepsy (TLE) often experience diminished quality of life (QoL). Although comorbid depression is one of the most recognized predictors of poor QoL in TLE, impairments in verbal memory (VM) and executive functioning (EF), have also been identified as risk factors, independent of other biological and psychosocial factors. In this study, we examine the contribution of depression, VM, and EF to QoL in 52 well-characterized medically-refractory TLE patients. METHODS: Quality of life was assessed with the Quality of Life in Epilepsy (QOLIE-31) questionnaire and depression symptomatology was evaluated with the Beck Depression Inventory-II (BDI-II). Tests of VM included the California Verbal Learning Test-Second Edition and the Wechsler Memory Scale-Third Edition, Logical Memory and Verbal Paired Associates subtests. Tests of EF included the D-KEFS Category Switching and Color Word Interference Tests, and the Trail Making Test. Using these measures, a principal component (PC) was derived for VM and for EF. Hierarchical multiple linear regression analysis was used to evaluate the unique contributions of BDI-II Score, VM PC, and EF PC to the QOLIE-31 Total Score, while controlling for important clinical and demographic variables. Post-hoc analyses were also performed to examine the contribution of each variable to specific QOLIE subscales. RESULTS: Of the clinical variables, only number of antiepileptic drugs contributed to QOLIE scores. As expected, severity of depressive symptoms was the most significant predictor of QOLIE Total Score, explaining 43.4% of the variance in total QoL. The VM PC did not contribute to the QOLIE Total Score. Rather, our EF PC emerged as an important predictor of QoL, explaining an additional 5% of the variance, after controlling for clinical variables, depression severity, and VM performance. SIGNIFICANCE: These findings suggest that a combination of clinical, affective, and cognitive factors influence QoL in patients with TLE. Designing interventions with careful attention to depression and EF may be needed to optimize QoL in patients with refractory TLE and potentially other epilepsy syndromes.

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.

Levels of processing effects on recognition memory in patients with schizophrenia.

This study sought to characterize the performance of patients with schizophrenia, as compared with healthy participants, on a memory task that required encoding of items to different depths. Participants included 21 individuals with schizophrenia and 26 healthy controls. During the encoding phase of the study, participants processed successively presented words in two ways: perceptually (by making a decision as to whether the letter "a" was present in the word) or semantically (by making a living/nonliving decision for each word). During the recognition phase of the study, participants were presented with a list of words containing items that had been presented during the encoding phase (during either the letter decision task or the semantic decision task), as well as items that had not been seen before (foils). Though patients with schizophrenia performed more poorly overall on the recognition task, recognition was facilitated by semantic encoding to an equivalent degree in both groups. In other words, while significant main effects were present for group and encoding, no groupxencoding condition was present. This result is consistent with previous findings of a lack of qualitative differences in performance on learning and memory tasks between patients with schizophrenia and healthy controls. It also suggests that strategies that place constraints on the encoding processes used by patients may help improve the efficiency with which they learn and remember information.

Face and place processing in Williams syndrome: evidence for a dorsal-ventral dissociation.

Individuals with Williams syndrome (WMS) show an interesting dissociation of ability within the visuospatial domain, particularly between face perception and other visuospatial tasks. In this population, using tasks matched for stimuli, required response, and difficulty (for controls) is critical when comparing performance across these areas. We compared WMS individuals with a sample of typically developing 8- and 9-year-old children, and with a sample of adults, closer to the WMS participants in chronological age, in order to investigate performance across two precisely matched perceptual tasks, one assessing face processing and the other assessing proficiency in processing stimuli location. The pattern of performance seen in WMS, but not in controls, implicates a specific deficit of dorsal stream functioning in this syndrome.

Reduced verbal fluency for proper names in nondemented patients with Parkinson's disease: a quantitative and qualitative analysis.

There has been an increasing interest within neuropsychology in comparing verbal fluency for different grammatical classes (e.g., verb generation vs. noun generation) in neurological populations, including Parkinson's disease (PD). However, to our knowledge, few studies have compared verbal fluency for common nouns and proper names in PD. Common nouns and proper names differ in terms of their semantic characteristics, as categories of common nouns are organized hierarchically based on semantics, while categories of proper nouns lack a well-defined semantic organization. In addition, there is accumulating evidence that the retrieval of these distinct grammatical classes are subserved by somewhat distinct neural systems. Given that verbal fluency deficits are among the first impairments to emerge in PD, and that such deficits are predictors of future cognitive decline, it is important to examine all aspects of verbal fluency in this population. For the current study, we compared the performance of a group of 32 nondemented PD patients with 32 healthy participants (HP) on verbal fluency tasks for common nouns (animals) and proper names (boys' first names). A significant interaction between verbal fluency task and diagnostic status emerged, as the PD group performed significantly worse on only the proper name fluency task. This finding may reflect the absence of well-defined semantic organization that structures the verbal search for first names, thus placing a greater onus on strategic or "executive" verbal retrieval processes.

Amygdala response to faces parallels social behavior in Williams syndrome.

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder.