Search

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.

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.

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.

Objective/methods Neuroimaging research has predominantly focused on exploring how cortical or subcortical brain abnormalities are related to language dysfunction in patients with neurological disease through the use of single modality imaging. Still, limited knowledge exists on how various MRI measures relate to each other and to patients' language performance. In this study, we explored the relationship between measures of regional cortical thickness, gray–white matter contrast (GWMC), white matter diffusivity [mean diffusivity (MD) and fractional anisotropy (FA)] and the relative contributions of these MRI measures to predicting language function across patients with temporal lobe epilepsy (TLE) and healthy controls. T1- and diffusion-weighted MRI data were collected from 56 healthy controls and 52 patients with TLE. By focusing on frontotemporal regions implicated in language function, we reduced each domain of MRI data to its principal component (PC) and quantified the correlations among these PCs and the ability of these PCs to explain the variation in vocabulary, naming and fluency. We followed up our significant findings by assessing the predictive power of the implicated PCs with respect to language impairment in our sample. Results We found significant positive associations between PCs representing cortical thickness, GWMC and FA that appeared to be partially mediated by changes in total brain volume. We also found a significant association between reduced FA and increased MD after controlling for confounding factors (e.g., age, field strength, total brain volume). Reduced FA was significantly associated with reductions in visual naming while increased MD was associated with reductions in auditory naming scores, even after controlling for the variability explained by reductions in hippocampal volumes. Inclusion of FA and MD PCs in predictive models of language impairment resulted in significant improvements in sensitivity and specificity of the predictions. Conclusions Quantitative MRI measures from T1 and diffusion-weighted scans are unlikely to represent perfectly orthogonal vectors of disease in individuals with epilepsy. On the contrary, they exhibit highly intercorrelated PCs in their factor structures, which is consistent with an underlying pathological process that affects both the cortical and the subcortical structures simultaneously. In addition to hippocampal volume, the PCs of diffusion weighted measures (FA and MD) increase the sensitivity and specificity for determining naming impairment in patients with TLE. These findings underline the importance of combining multimodal imaging measures to better predict language performance in TLE that could extend to other patients with prominent language impairments., Highlights • We integrate structural and diffusion MRI data from TLE patients and controls. • We use PCA to characterize disease-related volumetric and tract-based changes. • Increased left hemisphere FA is associated with worse visual naming. • Decreased left hemisphere MD is associated with worse auditory naming. • Using diffusion-based MRI metrics improves prediction of language function in TLE.

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.

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 remain unknown. This study investigated the relationship between cortical thinning, white matter compromise, epilepsy variables, and the side of seizure onset, in patients with TLE.

Neural circuits mediating repetition effect for semantically congruous words on functional MRI were investigated in seventeen normal elderly (mean age = 70). Participants determined if written words were semantically congruent (50% probability) with spoken statements. Subsequent cued-recall revealed robust explicit memory only for congruous items (83% versus 8% for incongruous). Event-related BOLD responses to New > Old congruous words were found in the left > right cingulate and fusiform gyri, left parahippocampal cortex, middle and inferior frontal gyri (IFG). A group with above-median subsequent recall had markedly more widespread BOLD responses than a Low-Recall subgroup, with larger responses in the left medial temporal lobe (LMTL), IFG, and bilateral cingulate gyri. The magnitude of LMTL activation (New–Old) correlated with subsequent cued-recall, while the spatial extent of LMTL activation (New > Old) correlated with recall and recognition. Both magnitude and spatial extent of left fusiform activation correlated with subsequent recall/recognition. A neural circuit of left-hemisphere brain regions, many identified as P600 generators by invasive electrophysiological studies, was activated by New > Old congruous words, likely mediating successful verbal encoding.

Objective: To investigate postoperative changes in fiber tract integrity in patients with temporal lobe epilepsy (TLE) following anterior temporal lobectomy (ATL) and to determine whether postoperative changes are 1) stable vs progressive and 2) related to visual field defects. Methods: Diffusion tensor imaging (DTI) was obtained in 7 patients with TLE before, 2 months after, and 1 year after ATL. Changes in fractional anisotropy (FA) were evaluated in a whole-brain voxel-wise analysis, as well within specific fiber tracts. Repeated-measures analysis of variance was performed to examine the time course of FA changes within ipsilateral and contralateral fiber tracts. Quantitative visual field analysis was performed to determine whether decreases in regional FA were related to the extent or location of visual field defects. Results: Patients showed decreased FA 2 months post-ATL in ipsilateral fiber tracts transected during surgery (parahippocampal cingulum, uncinate fasciculus, inferior longitudinal fasciculus, and fornix), as well as in fiber tracts not directly transected (inferior fronto-occipital fasciculus and corpus callosum). Additional decreases in FA were not observed from 2 months to 1 year post-ATL. Visual field defects in most patients were characterized by incomplete quadrantanopsias. However, FA reductions in one patient extended into temporo-occipital cortex and the splenium of the corpus callosum and were associated with a complete hemianopia. Conclusions: Wallerian degeneration is apparent 2 months following unilateral ATLs in ipsilateral fibers directly and indirectly affected during surgery. These changes do not appear to progress over the course of a year, but may correlate with the nature and extent of postoperative visual field defects.

The ability to interpret nonliteral, metaphoric language was explored in patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), and matched control participants, to determine (1) if patients with FLE were impaired in their interpretations relative to those with TLE and controls, and (2) if disease-related variables (e.g., age of seizure onset) predicted performances in either patient group. A total of 22 patients with FLE, 20 patients with TLE, and 23 controls were administered a test of proverb interpretation to assess their ability to grasp the abstract meaning of nonliteral language. Participants were presented with a series of proverbs and asked to provide an oral interpretation of each. Responses to each proverb were scored according to their accuracy and level of abstractness. Patients with FLE, but not TLE, were impaired relative to controls in their overall interpretation of proverbs. However, a subgroup analysis revealed that only patients with left FLE showed impaired interpretation accuracy relative to the other groups, whereas patients with both left FLE and left TLE showed impaired abstraction. Patients with FLE were also impaired when they were asked to select the best interpretation of the proverb from response alternatives. In patients with FLE, only a left-sided seizure focus was associated with poorer performance. In patients with TLE, both an early age of onset and a left-sided seizure focus predicted poorer performance. Overall, FLE patients exhibit greater impairment than TLE patients in interpreting proverbs. However, the nature and disease-specific correlates of impaired performances in proverb interpretation differ between the groups.

To determine the validity and utility of using automated subcortical segmentation to identify atrophy of the hippocampus and other subcortical and cerebellar structures in patients with mesial temporal lobe epilepsy (MTLE).Volumetric MRIs were obtained on 21 patients with MTLE (11 right, 10 left) and 21 age- and gender-matched healthy controls. Labeling of subcortical and cerebellar structures was accomplished using automated reconstruction software (FreeSurfer). Multivariate analysis of covariance (MANCOVA) was used to explore group differences in intracranial-normalized, age-adjusted volumes and structural asymmetries. Step-wise discriminant function analysis was used to identify the linear combination of volumes that optimized classification of individual subjects.Results revealed the expected reduction in hippocampal volume on the side ipsilateral to the seizure focus, as well as bilateral reductions in thalamic and cerebellar gray matter volume. Analysis of structural asymmetries revealed significant asymmetry in the hippocampus and putamen in patients compared to controls. The discriminant function analysis revealed that patients with right and left MTLE were best distinguished from one another using a combination of subcortical volumes that included the right and left hippocampus and left thalamus (91-100% correct classification using cross-validation).Volumetric data obtained with automated segmentation of subcortical and cerebellar structures approximate data from previous studies based on manual tracings. Our data suggest that automated segmentation can provide a clinically useful means of evaluating the nature and extent of structural damage in patients with MTLE and may increase diagnostic classification of patients, especially when hippocampal atrophy is mild.

Gamma knife surgery (GKS) is a radiation procedure recently used in the treatment of temporal lobe epilepsy (TLE). Preliminary studies have shown significant seizure reductions in patients 8-26 months postprocedure; however, little is known about the effect of GKS on cognitive functioning in TLE. We report neuropsychological data on three patients with left TLE and MRI evidence of hippocampal sclerosis who underwent GKS. Two models for assessing cognitive change, reliable change indices and regression-based norms for change, were used to measure preoperative versus 13- to 27-month postoperative cognitive change. Results revealed a significantly long delayed verbal memory decline on one measure following GKS. No patient declined on measures of IQ, visual memory, or language. Radiation-induced edema was present at the time of testing in all three patients, which may have affected verbal memory performance. While preliminary, these data suggest that GKS offers a less invasive option to anterior temporal lobectomy, but may produce neuropsychological changes similar to those produced by left anterior temperol lobectomy up to 2 years post-GKS treatment.

It has been reported that patients with amnesia have a reduced effect of word repetition upon the late positive component of the event related potential (ERP), which peaks at around 600 ms after word onset.To study a word repetition ERP paradigm in subjects with mild cognitive impairment.14 patients with mild cognitive impairment (mean mini-mental state examination score = 27); 14 normal elderly controls.Auditory category statements were each followed by a single visual target word (50% "congruous" category exemplars, 50% "incongruous") while ERPs were recorded. N400 (an ERP component elicited by semantically "incongruous" words) and LPC amplitude data were submitted to analysis of variance.The latency of the N400 was slower in mild cognitive impairment. In normal controls, the ERPs to "congruous" targets showed a late positive component to new words, which was greatly diminished with repetition. This repetition effect in normal subjects started before 300 ms at right frontal sites, and peaked at approximately 600 ms post-stimulus over posterior sites. In contrast, the group with mild cognitive impairment had a reduced repetition effect (p0.02), which started around 500 ms, with a more central distribution. Further comparisons within the cognitive impairment group showed no appreciable congruous word repetition effect among seven individuals who subsequently converted to probable Alzheimer's disease. The congruous word repetition effect in the group with mild cognitive impairment was almost entirely accounted for by the non-converters. The amplitude of the congruous late positive component word repetition effect was significantly correlated (0.38or = ror = 0.73) with several verbal memory measures.The congruous word repetition ERP effect appears sensitive to the memory impairment in mild cognitive impairment and could have value in predicting incipient Alzheimer's disease.

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.

Eye movements, eye blinks, cardiac signals, muscle noise, and line noise present serious problems for electroencephalographic (EEG) interpretation and analysis when rejecting contaminated EEG segments results in an unacceptable data loss. Many methods have been proposed to remove artifacts from EEG recordings, especially those arising from eye movements and blinks. Often regression in the time or frequency domain is performed on parallel EEG and electrooculographic (EOG) recordings to derive parameters characterizing the appearance and spread of EOG artifacts in the EEG channels. Because EEG and ocular activity mix bidirectionally, regressing out eye artifacts inevitably involves subtracting relevant EEG signals from each record as well. Regression methods become even more problematic when a good regressing channel is not available for each artifact source, as in the case of muscle artifacts. Use of principal component analysis (PCA) has been proposed to remove eye artifacts from multichannel EEG. However, PCA cannot completely separate eye artifacts from brain signals, especially when they have comparable amplitudes. Here, we propose a new and generally applicable method for removing a wide variety of artifacts from EEG records based on blind source separation by independent component analysis (ICA). Our results on EEG data collected from normal and autistic subjects show that ICA can effectively detect, separate, and remove contamination from a wide variety of artifactual sources in EEG records with results comparing favorably with those obtained using regression and PCA methods. ICA can also be used to analyze blink-related brain activity.

Objectives : To characterize the effects of normal aging on the amplitude, latency and scalp distribution of the N400 congruity effect. Methods : Event-related brain potentials (ERPs) were recorded from 72 adults (half of them men) between the ages of 20 and 80 years (12/decade) as they performed a semantic categorization task. Participants listened to spoken phrases (e.g. `a type of fruit' or `the opposite of black') followed about 1 s later by a visually-presented word that either did or did not fit with the sense of the preceding phrase; they reported the word read and whether or not it was appropriate. ERP measurements (mean amplitudes, peak amplitudes, peak latencies) were subjected to analysis of variance and linear regression analyses. Results : All participants, regardless of age, produced larger N400s to words that did not fit than to those that did. The N400 congruity effect (no-fit ERPs−fit ERPs) showed a reliable linear decrease in the amplitude (0.05–0.09 μ V per year, r =0.40) and a reliable linear increase peak latency (1.5–2.1 ms/year, r =0.60) with age. Conclusions : In sum, the N400 semantic congruity effect at the scalp gets smaller, slower and more variable with age, consistent with a quantitative rather than qualitative change in semantic processing (integration) with normal aging.

The N400 congruity effect (event-related brain potential (ERP) 300–500 ms poststimulus onset to contextually incongruent minus congruent words) generally shows a linear amplitude decrease with normal aging, and an even greater decrease in Alzheimer's dementia. As little is known about N400 effects in Parkinson's disease (PD), we recorded ERPs in 11 elderly patients with PD (without dementia, mean age = 66 years) during antonymic and category verification. Nondemented PD patients exhibited larger N400 congruity effects than their age-matched controls, consistent with reports of behavioral hyperpriming and possibly insufficient inhibition of irrelevant semantic information and/or greater target activation. It is also consistent with abnormally heavy reliance in PD on external cues. These findings implicate abnormal dopaminergic signaling (e.g., frontostriatal and/or mesocortical circuits) in PD, despite l -dopa therapy.

The N400, an event-related brain potential (ERP) sensitive to semantic congruity, has been reported to have increased latency and/or reduced amplitude in young adults with schizophrenia. Little is known, however, regarding the N400 in older schizophrenia patients, especially those with late onset. We studied 18 middle-aged and elderly patients with schizophrenia and related psychoses (nine with early-onset psychosis (EOP) and nine with late-onset psychosis (LOP), and nine normal comparison (NC) subjects. Subjects read words which were semantically incongruent (50%) or congruent (50%) with a preceding spoken phrase which defined either an antonymic or categorical relationship. The LOP group had a significantly later peak latency of the N400 congruity effect compared to the NC group. Seven of 18 psychosis patients, but none (0/9) of the normal subjects, had an abnormal latency or amplitude ( p = 0.04), measured at T6 (right temporal). Smaller amplitudes were associated with more severe negative symptoms ( r p = 0.58; p = 0.01). N400 abnormalities in older schizophrenia patients likely reflect abnormal processing of semantic information.

Summary: Purpose: Regional cortical dysfunction associated with epileptogenic activity was predicted from interic-tal localized abnormal low frequency neuromagnetic activity (ALFMA) using Magnetic Source Imaging (MSI). ALFMA can be detected in patients who show no interictal spikes. Methods: A large array biomagnetometer was used in a blinded, rapid screening protocol. The MSI procedure required no alteration in epileptic medications. MSI results were compared with the presumed epileptogenic region as determined by a consensus of standard techniques, which included MR and electroclinical monitoring. Results: One or more sites of localized abnormality were detected by MSI ALFMA in 29 of the 33 epileptic patients. ALFMA mapped with MSI showed a 48.5% specificity with respect to the presumed epileptogenic region. MSI ALFMA was in agreement with the final consensus as often as was ictal noninvasive video EEG monitoring, and was exceeded in specificity overall only by invasive ictal video EEG monitoring, which was required for conventional localization in 21 of the 33 patients tested with MSI. Conclusions: ALFMA measurements with MSI may augment the array of noninvasive methods used for reaching a consensus for epilepsy surgery.

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.

To assess the effects of normal aging and senile dementia of the Alzheimer's type (SDAT) on semantic analysis of words, we examined the N400 component of the event-related potential (ERP) elicited during the processing of highly constrained (opposites) and less constrained materials (category-category exemplars) in 12 young control subjects, 12 elderly control subjects and 12 patients with SDAT. We employed a priming paradigm in which a context phrase was spoken and a target word (congruent or incongruent) was presented visually. The N400 effect was reduced in amplitude and delayed in the elderly control group relative to that of the younger subjects, and was further attenuated in amplitude, delayed in latency and somewhat flatter in its distribution across the scalp in the SDAT patients. These findings are consistent with less efficient processing and integration of lexical items with semantic context in normal aging, which is further exacerbated by SDAT. Differences in the N400 range associated with the opposite and category conditions were observed only in the young subjects, suggesting less use of controlled attentional resources or perhaps weaker associative links with age.

Neurological function in 159 subjects infected by the human immunodeficiency virus (HIV) who had no neurological symptoms or signs (129 asymptomatic, 30 with ARC/AIDS) was compared to that of 62 controls by means of pattern-reversal evoked potentials (PREPs), brain-stem auditory evoked potentials (BAEPs), median nerve somatosensory evoked potentials (MSEPs), tibial nerve somatosensory evoked potentials (TSEPs) and nerve conduction studies (NCSs). Central nervous system somatosensory conduction from lumbar cord to cortex was prolonged in both asymptomatic seropositive and ARC/AIDS groups, while peripheral somatosensory conduction, NCSs and PREP delays occurred only in the ARC/AIDS group. BAEPs did not show significant differences among groups. TSEPs were abnormal in 8% of asymptomatic carriers and 43% of patients with ARC/AIDS, MSEPs in 7% and 20%, PREPs in 4% and 0%, and BAEPs in 1% and 0% respectively. One or more evoked potentials were abnormal in 18 of 129 (14%) asymptomatic carriers and 13 of 30 (43%) subjects with ARC/AIDS as compared with 1 of 62 (2%) seronegative controls. We conclude that asymptomatic HIV carriers have subclinical neurological impairment of central somatosensory function and that the neurological impairment increases with disease progression to involve peripheral nerves and visual system.

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.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.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.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.

A detailed neuropsychological evaluation was performed on a patient with an idiopathic cerebellar degenerative disorder. Significant deficits were found in verbal and nonverbal intellegence, verbal associative learning, and visuospatial skills. These deficits were not readily explained by motor control difficulties. In contrast to the patient's moderately impaired language abilities, he was severely impaired on a test of verbal fluency and demonstrated mild naming deficits. Severe cerebellar parenchymal volume loss was demonstrated by magnetic resonance examination. Supratentorial structures showed only minimal posterior parietal and occipital sulcal prominence. On neurological examination, this patient had signs of severe involvement of the cerebellar systems and mild-to- moderate dysfunction of the corticospinal tract. As is characteristic of patients with cerebellar degeneration, there was neurophysiological evidence of subclinical involvement of auditory and somatosensory pathways at the level of the brain stem. Since relatively little cerebral cortical atrophy was noted in this patient, these findings suggest that an intact cerebellum is important for normal cognitive functions.

BACKGROUND AND PURPOSE: Noninvasive imaging plays a pivotal role in lateralization of the seizure focus in presurgical patients with temporal lobe epilepsy (TLE). Our goal was to evaluate the utility of diffusion tensor imaging (DTI) tractography in TLE. MATERIALS AND METHODS: Twenty-one patients with TLE (11 right, 10 left TLE) and 21 controls were enrolled. A 1.5T MR imaging scanner was used to obtain 51 diffusion-gradient-direction images per subject. Eight pairs of white matter fiber tracts were traced, and fiber tract fractional anisotropy (FA) was calculated and compared with controls. Fiber tract FA asymmetry and discriminant function analysis were evaluated in all subjects and fiber tracts respectively. RESULTS: Compared with controls, patients with TLE demonstrated decreased FA in 5 ipsilateral fiber tracts. Patients with left TLE had 6 ipsilateral and 4 contralateral fiber tracts with decreased FA. Patients with right TLE had 4 ipsilateral but no contralateral tracts with decreased FA compared with controls. Right-sided FA asymmetry was demonstrated in patients with right TLE for 5 fiber tracts, and left-sided asymmetry, for patients with left TLE for 1 fiber tract. Discriminant function analysis correctly categorized patients into left-versus-right TLE in 90% of all cases (100% correct in all patients without hippocampal sclerosis) by using uncinate fasciculus and parahippocampal fiber tracts. CONCLUSIONS: We found widespread reductions in fiber tract FA in patients with TLE, which were most pronounced ipsilateral to the seizure focus. Patients with left TLE had greater, more diffuse changes, whereas patients with right TLE showed changes that were primarily ipsilateral. Disease was lateralized to a high degree independent of identifiable hippocampal pathology noted on conventional MR imaging.

Objective: To investigate the relationship between white matter tract integrity and language and memory performances in patients with temporal lobe epilepsy (TLE). Methods: Diffusion tensor imaging (DTI) was performed in 17 patients with TLE and 17 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for six fiber tracts (uncinate fasciculus [UF], arcuate fasciculus [AF], fornix [FORX], parahippocampal cingulum [PHC], inferior fronto-occipital fasciculus [IFOF], and corticospinal tract [CST]). Neuropsychological measures of memory and language were obtained and correlations were performed to evaluate the relationship between DTI and neuropsychological measures. Hierarchical regression was performed to determine unique contributions of each fiber tract to cognitive performances after controlling for age and hippocampal volume (HV). Results: Increases in MD of the left UF, PHC, and IFOF were associated with poorer verbal memory in TLE, as were bilateral increases in MD of the AF, and decreases in FA of the right AF. Increased MD of the AF and UF, and decreased FA of the AF, UF, and left IFOF were related to naming performances. No correlations were found between DTI measures and nonverbal memory or fluency in TLE. Regression analyses revealed that several fibers, including the AF, UF, and IFOF, independently predicted cognitive performances after controlling for HV. Conclusions: The results suggest that structural compromise to multiple fiber tracts is associated with memory and language impairments in patients with temporal lobe epilepsy. Furthermore, we provide initial evidence that diffusion tensor imaging tractography may provide clinically unique information for predicting neuropsychological status in patients with epilepsy. GLOSSARY: AF = arcuate fasciculus; BNT = Boston Naming Test; CST = corticospinal tract; DTI = diffusion tensor imaging; FA = fractional anisotropy; FORX = fornix; HV = hippocampal volume; ICHV = intracranial-adjusted HV; IFOF = inferior fronto-occipital fasciculus; LM = Logical Memory; MD = mean diffusivity; MTS = mesial temporal sclerosis; PHC = parahippocampal cingulum; TLE = temporal lobe epilepsy; UF = uncinate fasciculus; WMS-III = Wechsler Memory Scale–Third Edition.

Summary Purpose: To determine the nature and extent of regional cortical thinning in patients with mesial temporal lobe epilepsy (MTLE). Methods: High-resolution volumetric MRIs were obtained on 21 patients with MTLE and 21 controls. Mean cortical thickness was measured within regions of interest and point-by-point across the neocortex using cortical reconstruction and parcellation software. Results: Bilateral thinning was observed within frontal and lateral temporal regions in MTLE patients relative to controls. The most striking finding was bilateral cortical thinning in the precentral gyrus and immediately adjacent paracentral region and pars opercularis of the inferior frontal gyrus, extending to the orbital region. Within the temporal lobe, bilateral thinning was observed in Heschl's gyrus only. Ipsilateral only thinning was observed in the superior and middle temporal gyri, as well as in the medial orbital cortex. Greater asymmetries in cortical thickness were observed in medial temporal cortex in patients relative to controls. Individual subject analyses revealed that this asymmetry reflected significant ipsilateral thinning of medial temporal cortex in 33% of patients, whereas it reflected ipsilateral thickening in 20% of MTLEs. Discussion: Patients with MTLE show widespread, bilateral pathology in neocortical regions that is not appreciated on standard imaging. Future studies are needed that elucidate the clinical implications of neocortical thinning in MTLE.

The brain-stem auditory evoked potential (BAEP), a sensitive test of the functional status of the neonatal brain, has not been studied in utero since no practical technique for human fetal recording is available. We have developed a simple recording technique which allows continuous monitoring of the fetal AEP during labor. Waves I, III and V of the fetal brain-stem AEP have been consistently identified. Wave form morphology, interpeak latencies, and latency-intensity relations are similar to postnatal recordings. Middle latency potentials have also been recorded, with wave forms that correspond to the neonatal middle latency AEP.

Two patients, ages 51 and 76 years, suddenly developed transcortical motor aphasia combined with pyramidal signs and ataxia of the right extremities that affected the leg more severely than the arm. Computed tomography revealed nonenhancing lucencies in the distribution territory of the left anterior cerebral artery involving the genu of the corpus callosum, white matter ventral to the left frontal horn, medial primary motor area, supplementary motor area, and superior part of the premotor area. It is postulated that aphasia, ataxia, and weakness resulted from involvement of the supplementary motor area and deep white matter, premotor, and primary motor areas, respectively. Anterior cerebral artery infarctions of the dominant hemisphere may result in transcortical motor aphasia associated with contralateral ataxic hemiparesis.

Patients with frontal-lobe epilepsy (FLE) or temporal-lobe epilepsy (TLE) and matched control participants were given a design fluency test that assessed nonverbal fluency and switching ability. Patients with FLE generated fewer designs in the switching condition relative to the TLE patients and controls, whereas group differences did not emerge in the basic fluency conditions. When the side of the seizure focus and the presence or absence of a structural lesion were considered in patients with FLE, only those with left-lesional FLE generated fewer designs than controls did in the switching condition. Furthermore, patients with left-lesional and nonlesional FLE produced a greater proportion of set-loss errors than did controls. These results indicate that patients with FLE are impaired when they must simultaneously generate new designs and engage in cognitive switching; however, the pattern of impairment may depend on the side of the seizure focus and the presence of a structural lesion.

Vagus nerve stimulation (VNS) for epilepsy has been available in the United States for 8 years. Pivotal randomized, blinded clinical trials leading to FDA approval in patients age 12 and older with refractory partial seizures have not been performed for other age groups or epilepsy syndromes. This practical review takes stock of the current information about VNS use and efficacy in various types of epilepsy. We review the evidence for commonly used stimulation parameters, end of battery life, predictors of response including duration of epilepsy, seizure type/epilepsy syndrome, bihemispheric seizures, age at implant, and prior cranial surgery. We review adverse events and VNS effects on respiratory patterns, cardiac function, and mood and behavior. With the recent U.S. approval of VNS for treatment-resistant depression, we anticipate that lessons learned from treating patients with epilepsy will be useful to physicians using VNS to treat patients with depression and possibly other conditions.

We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% “congruous” (category exemplars) and 50% “incongruous” (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from ∼10–140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

Auditory P300 amplitude reductions are well-established in young adults with schizophrenia. Little is known, however, regarding the P300 in older schizophrenia patients, especially those with late onset. We studied 28 middle-aged and elderly (mean age=62.7 years) patients [14 with early onset schizophrenia (EOS) and 14 with late onset schizophrenia (LOS)] and 14 normal comparison (NC) participants using an auditory oddball paradigm. Event-related potentials were recorded from 15 scalp electrodes and six non-scalp sites. There were no significant differences between EOS and LOS groups in neuroleptic dosage, symptom severity, reaction times, target-detection accuracy, or N100 and N200 ERP measures. The EOS, but not the LOS, group had significantly smaller auditory oddball P300 amplitudes than the NC group. Twelve of the 14 LOS patients had P300 amplitudes in the normal range. Smaller P300 amplitudes were associated with earlier age of onset ( r =0.48), longer duration of illness ( r =−0.49) and more severe alogia ( r =−0.50). We conclude that P300 abnormalities in schizophrenia may be a marker for a disease subtype with early onset and more severe information-processing deficits.

Event-related brain potentials (ERPs) were recorded from 74 subjects (45 men) between 18 and 82 years of age in a simple visual detection task. On each trial the subject reported the location of a triangular flash of light presented briefly 20° laterally to the left or right visual field or to both fields simultaneously. ERPs to targets exhibited a similar morphology including P1, N1, P2, N2, and P3 components across all age groups. The principal effects of advancing age were (1) a marked reduction in amplitude of the posterior P1 component (75–150 latency) together with an amplitude increase of an anterior positivity at the same latency; (2) an increase in amplitude of the P3 component that was most prominent over frontal scalp areas; and (3) a linear increase in P3 peak latency. These results extend the findings of age-related changes in P3 peak latency and distribution to a non-oddball task in the visual modality and raise the possibility that short-latency ERPs may index changes in visual attention in the elderly.

Two patients with simple partial epileptic seizures were able to abate their attacks by vigorous somatosensory stimulation of the body part initially involved by the seizure. In both patients, the seizure symptoms progressed in a marching fashion which suggests a gradual spread of the epileptic discharge from its initial locus to adjacent areas.

• Charles Bouchard, an ambitious and industrious man, was one of Jean Martin Charcot's first pupils. With his mentor's support, he rapidly ascended the academic ladder and became a full professor at the school of medicine in Paris. After Bouchard attained professorship, his relationship with Charcot gradually deteriorated. Their strong personalities, their ambition to have schools of their own, and their competition to become the most influential man in the medical school resulted in antagonism between them. The most tragic consequence of this antagonism took place in 1892 when Bouchard presided over the competitive examinations for agregation , in which Joseph Babinski, one of Charcot's youngest pupils, was a candidate. Charcot wanted his pupil to be nominated but Bouchard eliminated him in order to nominate his own pupils. The nominations were appealed but finally Bouchard's decision was upheld. Babinski did not retake the examination and never became a professor at the medical school.

Pattern reversal visual, brain-stem auditory, and short latency median nerve somatosensory evoked potentials (EPs) were evaluated in a prospective study over 4 years in 20 patients with clinically definite sclerosis (MS). Standardized neurological examinations were done at regular intervals and correlated with EP findings. The highest incidence of EP abnormalities occurred in the visual system followed by the somatosensory and auditory systems. Clinical relapse was usually accompanied by EP deterioration, but clinical improvement often occurred without parallel EP recovery. EP changes were not always related to clinical symptoms and often took place during remission periods in the absence of clinical changes. There was no significant correlation between clinical and electrophysiological progression within any given sensory modality. The progression of clinical disability, however, showed a fairly good correlation with the overall progression of EP abnormalities. We conclude that EPs complement the neurological exam in the evaluation of MS and may have a place in the investigation of the effects of therapeutic agents on the neurological status in MS.

Pattern electroretinograms (PERGs) were recorded in ten subjects employing two varieties of electrodes: a gold foil electrode inserted into the lower fornix, and a gold cup skin electrode overlying the inferior orbit. Recordings were obtained as subjects viewed a checker-board pattern that reversed with a frequency of 2.1 Hz. Check size varied from 4 degrees to 0.25 degrees, at a contrast of 98%. Two additional recordings were obtained with 0.5 degree check size, lower luminance, and lower contrast. The PERG recorded with a skin electrode was similar in configuration to the PERG recorded with a gold foil electrode, but smaller in amplitude. The equation relating the amplitude of the b-wave recorded from the foil electrode (y) to the amplitude of the b-wave recorded from the skin electrode (x) was: y = 0.127 + 2.150x, with an R value of 0.82. Latencies of both the a- and b-waves were comparable under both recording conditions. We conclude PERGs may be adequately recorded with a noncorneal skin ele...

Electrographic seizures (EGS) were detected in 13 of 16 asphyxiated neonates who were undergoing continuous electroencephalographic monitoring for detection of evidence of central nervous system injury. Five of the 13 neonates with EGS also had periodic lateralized epileptiform discharges (PLEDs). The electrographic characteristics of PLEDs in these infants were similar to those reported in neonatal herpes simplex encephalitis and in older children and adults. Of the 5 neonates with PLEDs, 2 died, 2 are developmentally delayed and only 1 is normal at 12 months. This is in contrast to the normal outcome for 8 of the 11 infants who did not have PLEDs. One other was neurologically normal but died of pulmonary disease at 3 months and the other two were developmentally delayed. PLEDs in neonates, as in other age groups, lack diagnostic specificity, but when associated with neonatal asphyxia, may indicate a poor prognosis. Continuous EEG monitoring is helpful in identifying PLEDs in these cases.

Summary: The relative efficacies of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and valproic acid (VPA) in the suppression of focal and generalized seizures produced by electrical stimulation of two different cortical sites (areas 3 and 10) were evaluated in the rat. The two cortical sites were distinguished by significantly different dose-response curve slopes for the suppression of afterdischarge duration by PHT, CBZ and VPA, which suggests more than one mechanism of action for these drugs. The dose-response curve slopes for PB, on the contrary, were not significantly different, although its potency was significantly greater in area 10. For suppression of generalized convulsions, dose-response curve slopes were not significantly different for any of the drugs. Potencies of PHT, CBZ and VPA were equivalent in the two areas, but PB was significantly more potent in the suppression of generalized convulsions triggered from area 10. It is concluded that focal seizures elicited by the stimulation of different cortical sites are differentially refractory to antiepileptic drugs. RESUME L'efficacite relative du Phenobarbital (PB) de la phenyloine (PHT), de la Carbamazepine (CBZ) et de l'acide valproique (VPA) sur les crises focales et generalisees provoquees par la stimulation electrique de deux regions corticales differentes (aires 3 et 10) a eteevaluee chez le rat. Les deux regions corticales se distinguaient par des pentes de courbe dose-reponse significativement differentes en ce qui concerne le duree de la post-decharge pour la PHT, la CBZ et le VPA, ce qui suggere l'existence de plus d'un mecanisme d'action de ces substances. Les pentes de courbes dose-reponse pour le PB, au contraire, n'etaient pas significativement differentes, bien que son efficacite fut significativement plus grande dans l'aire 10. En ce qui concerne la suppression des convulsions generalisees les pentes de courbes dose-reponse n'etaient pas significativement differentes pour ces drogues. L'efficacite de la PHT, de la CBZ et du VPA etait equivalente dans les deux aires mais le PB etait significativement plus efficace sur les convulsions generalisees declenchees a partir de l'aire 10. II est conclu que les crises focales obtenues par la stimulation de differentes regions corticales sont refractaires aux drogues antiepileptiques de facon differente. RESUMEN En las ratas se han valorado las eficacias relativas del feno-barbital (PB), fenitoina (PHT), carbamacepina (CBZ), y el acido valproico (VPA) con respecto a la supresion de los ataques focales y generalizados producidos por la estimulacion electrica de dos zonas corticales diferentes (areas 3 y 10). Estas dos zonas corticales se distinguieron por existir una diferencia significativa en los perfiles de la curva dosis-respuesta que representa la supresion de la duracion de las postdescargas por la PHT, CBZ y VPA. Esto sugiere que estas medicaciones utilizan mas de un mecanismo de accion. Los perfiles de la curva dosis-respuesta del fenobarbital, por el contrario, no fueron significativamente diferentes a pesar de que su potencia fue significativamente mas elevada en el area 10. En lo que concierne a la supresion de las convulsiones generalizadas, los perfiles de la curva dosis-respuesta no fueron significativamente diferentes para ninguna de las medicaciones. Las potencias de la PHT, CBZ y VPA fueron equivalentes en las dos areas pero el PB fue significativamente mas potente en la supresion de las convulsiones generalizadas que se desencadenaban en el area 10. Se concluye que los ataques focales producidos por la estimulacion de diferentes zonas corticales tienen una capacidad refractaria diferente a diversas medicaciones anticonvulsivas. ZUSAMMENFASSUNG Die relative Wirkung von Phenobarbital (PB), Phenytoin (PHT), Carbamazepin (CBZ) und Valproinsaure (VPA) auf die Unterdruckung fokaler und generalisierter Anfalle durch elek-trische Stimulation zweier unterschiedlicher Kortexregionen (Area 3 und 10) wurden bei der Ratte untersucht. Die beiden Kortexregionen waren zu unterscheiden durch signifikant un-terschiedliche Verlaufe der Dosisantwortkurven fur die Unterdruckung der Dauer der Nachentladungen durch PHT, CBZ und VPA; das deutet auf mehr als einen Wirkmechanismus fur diese Medikamente. Der Verlauf der Dosisantwortkurven fur Phenobarbital hingegen, unterschied sich nicht signifikant, obwohl seine Starke in der Region 10 groser war. In der Unterdruckung generalisierter Anfalle war der Verlauf der Dosisantwortkurven fur keines dieser Medikamente signifikant unterschiedlich. Die Wirkungen von PHT, CBZ und VPA waren in Beiden Regionen vergleichbar aber Phenobarbital war eindeutig wirkungsvoller in der Unterdruckung der generalisierten Krampfe, die von der Area 10 getriggert wurden. Es wird gefolgert, das fokale Krampfe nach Stimulation unterschiedlicher kortikaler Regionen gegenuber Antiepileptika unterschiedlich refraktar sein konnen.

Recent advances in the field of sensory evoked potentials (EPs) have allowed assessment of function in regions of the nervous system that were previously inaccessible to noninvasive electrophysiologic study. Pattern visual and brainstem auditory EPs, respectively, are more sensitive to certain optic nerve or posterior fossa lesions than either clinical or laboratory tests. Short-latency somatosensory EPs from the upper and lower extremities are sensitive to pathology at cervicomedullary and thoracolumbar levels of the neuraxis as well as to suprasegmental lesions. This article reviews the development of these tests as clinically useful tools and the applications in which they have contributed most to the practice of adult neurology.

• A 49-year-old man with definite multiple sclerosis suffered an episode of right-sided trigeminal neuralgia (TN) of two weeks' duration, unaccompanied by any other clinical symptoms or signs of exacerbation. Serial evoked potentials, obtained before, during, and after TN, demonstrated developing abnormalities in brain-stem auditory evoked potentials from the right ear that disappeared in a delayed fashion after the clinical symptoms of TN had subsided. This rare combination of clinical and electrophysiologic abnormalities suggests a pontine demyelinating plaque involving the right trigeminal sensory root and the right lateral lemniscus.