Integration of multimodal MRI data via PCA to explain language performance.

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.

Role of frontotemporal fiber tract integrity in task-switching performance of healthy controls and patients with temporal lobe epilepsy.

The objective of this study is to investigate the relationships among frontotemporal fiber tract compromise and task-switching performance in healthy controls and patients with temporal lobe epilepsy (TLE). We performed diffusion tensor imaging (DTI) on 30 controls and 32 patients with TLE (15 left TLE). Fractional anisotropy (FA) was calculated for four fiber tracts [uncinate fasciculus (UncF), arcuate fasciculus (ArcF), dorsal cingulum (CING), and inferior fronto-occipital fasciculus (IFOF)]. Participants completed the Trail Making Test-B (TMT-B) and Verbal Fluency Category Switching (VFCS) test. Multivariate analyses of variances (MANOVAs) were performed to investigate group differences in fiber FA and set-shifting performances. Canonical correlations were used to examine the overall patterns of structural-cognitive relationships and were followed by within-group bivariate correlations. We found a significant canonical correlation between fiber FA and task-switching performance. In controls, TMT-B correlated with left IFOF, whereas VFCS correlated with FA of left ArcF and left UncF. These correlations were not significant in patients with TLE. We report significant correlations between frontotemporal fiber tract integrity and set-shifting performance in healthy controls that appear to be absent or attenuated in patients with TLE. These findings suggest a breakdown of typical structure-function relationships in TLE that may reflect aberrant developmental or degenerative processes.

Changes in fiber tract integrity and visual fields after anterior temporal lobectomy.

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.

Side matters: diffusion tensor imaging tractography in left and right temporal lobe epilepsy.

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.

Diffusion tensor imaging correlates of memory and language impairments in temporal lobe epilepsy.

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.

Abnormal verbal event related potentials in mild cognitive impairment and incipient Alzheimer's disease.

BACKGROUND: 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. OBJECTIVE: To study a word repetition ERP paradigm in subjects with mild cognitive impairment. SUBJECTS: 14 patients with mild cognitive impairment (mean mini-mental state examination score = 27); 14 normal elderly controls. METHODS: 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. RESULTS: 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 (p < 0.02), 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 (0.38 < or = r < or = 0.73) with several verbal memory measures. CONCLUSIONS: 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.

Word repetition in amnesia. Electrophysiological measures of impaired and spared memory.

Amnesic patients often show improved performance when stimuli are repeated, even in the absence of conscious memory for those stimuli. Although these performance changes are typically attributed to perceptual or motor systems, in some cases they may be related to basic language processing. We examined two neurophysiological measures that vary with word repetition in 12 amnesic patients and 12 control subjects: (i) a late positive component of the event-related potential (ERP) linked to conscious memory and (ii) the N400 component that varies with language comprehension. In each trial, the subject heard a category name, then viewed a word, and then decided whether the word was semantically congruous or incongruous (e.g. 'yes' for 'baby animal: cub'; 'no' for 'water sport: kitchen'). Recall and recognition testing at the end of the experiment showed that control subjects had better memory for congruous than for incongruous words, as did the amnesic patients, who performed less well overall. In contrast, amnesic patients were unimpaired on the category decisions required in each trial and, like the control subjects, showed a large N400 for incongruous relative to congruous words. Similarly, when incongruous trials were repeated after 0-13 intervening trials, N400s were reduced in both groups. When congruous trials were repeated, a late positive repetition effect was observed, but only in the control group. Furthermore, the amplitude of the late positive repetition effect was highly correlated with later word recall in both patients and controls. In the patients, the correlation was also observed with memory scores from standardized neuropsychological tests. These data are consistent with a proposed link between the late positive repetition effect and conscious memory. On the other hand, the N400 repetition effect was not correlated with episodic memory abilities, but instead indexed an aspect of memory that was intact in the amnesic patients. The preserved N400 repetition effect is an example of preserved memory in amnesia that does not easily fit into the categories of low-level perceptual processing or of motor learning. Instead, the sensitivity of the N400 to both semantic context and repetition may reflect a short-term memory process that serves language comprehension in realtime.

Relationship between auditory P300 amplitude and age of onset of schizophrenia in older patients.

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.

N400 abnormalities in late life schizophrenia and related psychoses.

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 (rp = 0.58; p = 0.01). N400 abnormalities in older schizophrenia patients likely reflect abnormal processing of semantic information.

Amebic meningoencephalitis caused by Balamuthia mandrillaris: case report and review.

Balamuthia mandrillaris, formerly referred to as a leptomyxid ameba, is a free-living ameba that has recently been identified as a cause of meningoencephalitis. Previously, only two genera, Naegleria and Acanthamoeba, were recognized as causes of central nervous system (CNS) infections in humans. In contrast to Naegleria, Balamuthia causes a subacute-to-chronic infection of the CNS. Distinct from Acanthamoeba, which appears to favor the immunocompromised host, Balamuthia is capable of infecting both healthy and immunosuppressed hosts. Retrospective analyses as well as an accumulation of newly identified cases have demonstrated that this ameba is an increasingly important pathogen to recognize. We report the isolation, histopathologic features, and confirmation by indirect immunofluorescence of B. mandrillaris in a case of fatal amebic meningoencephalitis.

Pattern electroretinograms and visual evoked potentials in HIV infection: evidence of asymptomatic retinal and postretinal impairment in the absence of infectious retinopathy.

Retinal microangiopathy associated with HIV infection is usually asymptomatic and escapes detection unless funduscopic examination is performed when evanescent cotton-wool spots are present. The aim of this study was to assess retinal and optic nerve/retrochiasmal function in HIV infection by means of electrophysiologic techniques that are sensitive to the detection of subclinical visual impairment. We studied transient and steady state pattern electroretinograms grams (PERGs) and pattern-reversal visual evoked potentials (PVEPs) in 21 HIV-negative controls and 33 HIV-positive subjects (16 with CD4 > or = 200/mL and 17 with CD4 < 200/mL) without visual symptoms or infectious retinopathy. HIV-positive subjects with CD4 > or = 200/mL had reduced amplitude of the transient PERG P1 potential, but no other latency or amplitude abnormalities. The HIV-positive group with CD4 < 200/mL had reduced P1 transient PERG amplitude, as well as latency delay of the transient PVEP. These findings suggest that HIV infection is associated with subclinical retinopathy and that, when severe immunosuppression occurs, both retinopathy and optic nerve/retrochiasmal dysfunction are present. Transient PERGs are more sensitive measures of visual system disease in HIV infection than are steady state responses.

Neurological dysfunction in asymptomatic HIV-1 infected men: evidence from evoked potentials. HNRC Group.

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.

Effects of aging on event-related brain potentials and reaction times in an auditory oddball task.

Auditory event-related potentials (ERPs) were recorded from 71 healthy individuals between 18 and 82 years of age during performance of a disjunctive reaction time task in an auditory oddball paradigm. The effects of aging on reaction times and on the latencies, amplitudes, and distributions of each of the main ERP components were examined. No significant slowing of the reaction times of the elderly subjects was observed in relation to the younger ones. The peak latencies of both the N1 and P2 components elicited by standard tones were slightly but significantly slowed with age. In the ERPs of target tones, the later, endogenous components (N2, P3, and SW) showed linear increases in latency as a function of age; the later the component, the longer the age-related delay. In general, aging was associated with less negativity (both N2 and SW) and more positivity (P3) over the anterior scalp, together with a smaller P3 and a more pronounced N2 over posterior scalp areas. Most of the effects observed in target ERPs were also evident in the difference waves derived from subtraction of the standard from the target ERPs, although the slope of the age-related latency increase of N2 was shallower and that of the P3 was steeper in the difference ERPs. These findings are discussed in relation to previous accounts of ERP changes with aging.

Self-abatement of simple partial epileptic seizures.

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.

Somatosensory dysfunction in cystic fibrosis.

Posterior tibial somatosensory evoked potentials were obtained in a group of cystic fibrosis patients and age-matched controls. A small but significant delay of the lumbar potential and larger delays of the early scalp potentials were observed. These findings are consistent with earlier pathological studies demonstrating involvement of the somatosensory system in cystic fibrosis.

Ataxic hemiparesis associated with transcortical motor aphasia.

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.

Serial recordings of multimodality evoked potentials in multiple sclerosis: a four year follow-up study.

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.