Cognitive deficits in acute mild ischemic stroke and TIA and effects of rt-PA.

Introduction: It is unknown if treatment with rt-PA in mild acute ischemic stroke (MIS) is associated with improvement in long term cognition. Methods: Forty-five patients with suspected acute mild stroke or transient ischemic attacks with NIHSS ≤6 were enrolled in a prospective cohort. Cognitive testing was performed within 24 h of symptom onset. Follow-up assessment was performed at Day 90 on 25 patients. Prestroke baseline cognition was based on age, years of education (YrE), history of cognitive impairment, and the Fazekas score. Results: Eighty-five percent patients with suspected MIS or TIA showed cognitive abnormalities within 24 h of onset. There was no significant difference in age, sex, Fazekas score, or YrE between rt-PA versus No-rt-PA groups (N = 8 vs. 17).Two sample t-test for change in performance in the WMS-III sub-tests (follow-up - baseline) ± SD, indicated a difference between rt-PA 0.74 ± 0.77 and no-rt-PA groups -0.02 ± 0.83 (P = 0.044). Logistic regression for predicting normal status using the mental control subtest, at follow-up showed an OR 8.96, CI 0.98-82.12 (P = 0.05) favoring the rt-PA group. Improvement in Mental Control at 90 days occurred in patients with low white matter disease compared to high white matter disease, 0.60 ± 0.46 (P = 0.048). A statistical trend was observed and suggested an improvement on SDMT and Trail Making tests, 1.43 ± 0.8 (P = 0.077). Conclusion: Suspected MIS and TIA patients have cognitive impairment within 24 h of onset. rt-PA administration might be associated with improvement on some cognitive tests at 90 days.

Changes in maps of language function and the integrity of the arcuate fasciculus after therapy for chronic aphasia.

A patient with chronic aphasia secondary to unilateral stroke in the left hemisphere underwent language testing, diffusion tensor imaging (DTI), and functional imaging using magnetoencephalography (MEG) at four time points: 3 weeks prior to, immediately prior to, immediately after, and 3 months after Constraint Induced Language Therapy (CILT). Performance on language tests involving visual naming and repetition of spoken sentences improved between the immediately prior to and immediately after CILT testing sessions, but not between the pre-CILT sessions. MEG activation in putative pre-morbid language areas of the left hemisphere and homotopic areas of the right hemisphere increased immediately after therapy, as did integrity within the arcuate fasciculus bilaterally. These changes were not evident between the two pre-CILT sessions. While some of these functional, neurophysiological and structural changes had regressed 3 months after therapy, all remained at or above baseline levels. Results provide evidence for an association between improvement in functional status and the increased integrity within a white matter tract known to be involved in language function and its contralateral homologue, as well as increased neurophysiological activity in areas that have the potential to subserve language function bilaterally.

Evidence for the solidarity of the expressive and receptive language systems: a retrospective study.

A strong tendency toward left hemisphere (LH) language dominance has been well established, as evidenced by the high prevalence of language impairment following sudden onset lesions in the LH. In the presence of progressive LH pathology, such as epilepsy, substantial deviations in language organization can occur. However, the question regarding whether reorganization involves both expressive and receptive language functions or only the one directly affected by the primary location of pathology has not been settled. Using Wada testing scores from 296 epilepsy patients and estimated rates of typical dominance in the normal population, we assessed the frequency with which left frontal and temporal pathology resulted in reorganization of only the expressive or receptive language function or both. The comparisons revealed: (1) a significantly higher prevalence of atypical organization (i.e., deviations from LH dominance) among the LH patients compared to normal population estimates and right hemisphere patients, and (2) that regardless of pathology location within the LH, the rates of atypical reorganization for both expressive and receptive language were essentially equal. These results constitute evidence that the two language functions are intimately yoked and that when disruption to the system results in reorganization, it usually yields functional changes throughout the system.

Changes in maps of language activity activation following melodic intonation therapy using magnetoencephalography: two case studies.

Two patients with chronic expressive aphasia underwent two blocks of melodic intonation therapy (MIT) each. Maps of language-specific neurophysiological activity were obtained prior to and after each MIT block during a covert action naming task using magnetoencephalography. Both patients exhibited increased left hemisphere activation after MIT. The patient who responded positively to therapy exhibited decreasing activation within areas of the right hemisphere homotopic to left hemisphere language areas compared to baseline after both blocks of MIT. In contrast, the patient who did not show improvement after therapy exhibited increasing activation in these areas of the right hemisphere after therapy. Results are consistent with hypotheses that melodic intonation therapy acts through promotion of left hemisphere activation.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Behavioral and neurophysiologic response to therapy for chronic aphasia.

UNLABELLED: Breier JI, Juranek J, Maher LM, Schmadeke S, Men D, Papanicolaou AC. Behavioral and neurophysiologic response to therapy for chronic aphasia. OBJECTIVE: To characterize the relationship between neurophysiologic changes in the brain and behavioral response to constraint-induced language therapy (CILT) by using magnetoencephalography (MEG). DESIGN: Case series. SETTING: Medical school. PARTICIPANTS: Patients (N=23) with chronic aphasia after first-time unilateral stroke in the left hemisphere. INTERVENTIONS: Constraint-induced language therapy administered for 3 hours 4 times per week for 3 weeks. Language testing and functional imaging during a language comprehension task using MEG before, immediately after, and 3 months after CILT with a subgroup of patients undergoing additional MEG scanning and language testing 3 weeks before CILT. MAIN OUTCOME MEASURES: The percent of correct information units and the number of late dipoles normalized to total activation. RESULTS: Three patterns of behavioral and neurophysiologic response to CILT were identified. Patients with significant improvement in language immediately after CILT who lost these gains at follow-up had greater right hemisphere activation than other patients at all MEG scanning sessions. Patients with significant improvement in language immediately after CILT who maintained these gains at follow-up exhibited an increase in left temporal activation after CILT, whereas patients who did not exhibit significant improvement in language after CILT exhibited comparably greater activation in left parietal areas. CONCLUSIONS: Results suggest that although the right hemisphere may support recovery of language function in response to therapy, this recovery may not be stable, and some participation of perilesional areas of the left hemisphere may be necessary for a stable behavioral response.

Aberrant cortical functionality and somatosensory deficits after stroke.

Damage and/or disconnection of the primary somatosensory cortex (SI) after stroke leads to deficits in touch perception. We used magnetoencephalography to test whether specific patterns of functionality of the somatosensory cortex are associated with different degrees of postacute somatosensory deficit. Nineteen postacute unilateral stroke patients suffering different degrees of somatosensory deficit (six nonexistent, six moderate, and seven severe) and eight aged-matched controls underwent high-resolution MRI and whole-head magnetoencephalography recordings of somatosensory-evoked fields and of spontaneous slow oscillatory activity. Amplitude of SI activation after tactile stimulation in the affected and nonaffected hemispheres and delta dipole density (DDD) in the postcentral areas were estimated and compared across the four groups. Severe postacute somatosensory deficit was accompanied, in all cases, with absence of SI responses to stimulation in the affected hand and a significant asymmetry in postcentral DDD toward the affected hemisphere. Patients with moderate sensory loss showed asymmetry in their postcentral DDD (four cases toward the affected hemisphere and two toward the unaffected) but no atypical amplitudes in SI activation. Recordings in stroke patients without somatosensory deficit did not differ from those obtained in controls for SI amplitude or postcentral DDD. In stroke patients, amplitude of SI responses and postcentral DDD show a negative correlation. Lack of activation of SI cortex after stimulation of the affected hand and spontaneous slow oscillatory activity in postcentral areas are neurophysiological correlates of somatosensory deficit in the postacute phase of stroke.

Neocortical reorganization in spina bifida.

Normal brain development throughout childhood and adolescence is usually characterized by decreased cortical thickness in the frontal regions as well as region-specific patterns of increased white matter myelination and volume. We investigated total cerebral volumes, neocortical surface area, and neocortical thickness in 16 children with a neural tube defect, spina bifida myelomeningocele (SB), and 16 age-matched typically developing controls using a semi-automated, quantitative approach to MRI-based brain morphometry. The results revealed no significant group differences in total cerebral volume. However, group differences were observed in the global distribution of distinct tissue classes within the cerebrum: the SB group demonstrated a significant 15% reduction in total white matter and a 69% increase in cerebrospinal fluid, with no differences in total gray matter. Group comparisons of neocortical surface area assessments were significantly smaller in the occipital regions for SB, with no significant group differences in the frontal regions. Group comparisons of cortical thickness measurements demonstrated reduced cortical thickness in all regions except the frontal regions, where the SB group exhibited an increase relative to the PC group. Although regional patterns of thinning may be associated with the mechanical effects of hydrocephalus, the overall reduction in white matter and increased neocortical thickness in the frontal regions suggest that SB reflects a long-term disruption of brain development that extends far beyond the neural tube defect in the first weeks of gestation.

Spatiotemporal patterns of brain activation during an action naming task using magnetoencephalography.

Eight right-handed subjects were asked to silently generate a verb to a visual stimulus while the magnetic flux normal to the scalp surface was recorded with a whole-head neuromagnetometer. The spatiotemporal patterns of activation in lateral occipital, inferior parietal, superior temporal, basal temporal, and inferior frontal cortices were estimated using minimum estimation, a distributed source analysis methodology. Although there was significant variability among subjects, averaged data indicated that latencies of peak activation in these regions of interest progressed from posterior to anterior. Peak latencies were earliest in lateral occipital cortex and latest in pars opercularis and pars triangularis in the inferior frontal gyrus. Lateralization of activation was strongest in pars opercularis, which is part of classical Broca's area, with activation being stronger in this area within the left hemisphere in every subject. Results provide support for the use of magnetoencephalography in conjunction with MNE analysis for the purpose of lateralizing and localizing language-specific activation in frontal areas as well as the study of the spatiotemporal parameters of brain activation associated with cognitive function.

Changes in language-specific brain activation after therapy for aphasia using magnetoencephalography: a case study.

A patient with chronic aphasia underwent functional imaging during a language comprehension task using magnetoencephalography (MEG) before and after constraint induced language therapy (CILT). In the pre- and immediate post-treatment (TX) scans MEG activity sources were observed within right hemisphere only, and were located in areas homotopic to left hemisphere language areas. There was a significant increase in activation in these areas between the two sessions. This change was not observed in an age-matched patient with chronic aphasia who underwent sequential language testing and MEG scanning across a similar time period without being administered therapy. In the 3-month post-TX scan bilateral activation was observed, including significant activation within the left temporal lobe. The changes in the spatial parameters of the maps of receptive language function after therapy were accompanied by improvement in language function. Results provide support, in the same individual, for a role for both hemispheres in recovery of language function after therapy for chronic aphasia.

Magnetoencephalographic studies of language reorganization after cerebral insult.

We review our experience with the application of magnetoencephalography (MEG) to the study of reorganization of the mechanisms supporting auditory language comprehension. In 3 studies, patient populations with cerebral insult of differing etiology, including epilepsy, surgical resection, and stroke, performed a running recognition task for spoken words while MEG data were collected using a whole-head magnetometer. Increased activation in the right hemisphere after left temporal lobectomy was associated with greater relative activation in that hemisphere preoperatively. Patients with chronic seizure disorder secondary to mesial temporal sclerosis exhibited a tendency toward an interhemispheric shift of language function, and those with epilepsy secondary to neoplasm showed a tendency toward an intrahemispheric shift. Patients with aphasia secondary to unilateral left-hemisphere stroke exhibited a more bilateral and diffuse overall profile of activation within the left hemisphere than control subjects of similar age. Taken together, results provide evidence that reorganization of cortex subserving auditory comprehension can occur well into the fifth and sixth decades and that the nature of the plastic response is dependent on variables such as premorbid language laterality, etiology, and, in specific groups, age at insult.

Functional imaging before and after constraint-induced language therapy for aphasia using magnetoencephalography.

Five patients with chronic aphasia underwent functional imaging using magnetoencephalography (MEG) before and after constraint-induced language therapy (CILT). Patients who responded well to CILT exhibited a greater degree of late MEG activation in posterior language areas of the left hemisphere and homotopic areas of the right hemisphere prior to therapy than those who did not respond well. Response to CILT, however, was positively correlated with the degree of pre-therapy MEG activity within posterior areas of the right hemisphere only on an individual basis.

Is basic memory structure invariant across epilepsy patient subgroups?

It is well known that epilepsy patients often exhibit material-specific deficits in memory for verbal versus nonverbal material. However, it is also apparent that such deficits are not always discernible, and that numerous factors may potentially moderate the degree to which fractionation between verbal and nonverbal material is evident. Using confirmatory factor analysis, we compared the relative fit of one-factor (general) and two-factor (material-specific) models of memory in data from 330 patients with intractable seizure disorder. Data from verbal and nonverbal selective reminding tests, as well as Logical Memory and Visual Reproduction (immediate and delayed recall indices), were used in analyses. The one-factor model fit the data poorly in the full sample, whereas the two-factor model fit the data significantly better. We then assessed the invariance of these two models using multiple-group modeling across subsamples of patients with left versus right sided seizure focus, earlier versus later age of seizure onset, lower versus higher Full Scale IQ, fewer versus more years of education, younger versus older patients, and male versus female patients. In all cases, the two-factor model comprised of verbal and nonverbal memory factors fit the data better than a one-factor (general) model. These findings indicate robust consistency of verbal and nonverbal memory constructs in the epilepsy population, which remain viable in this patient group despite considerable heterogeneity in other respects.

Toward the substitution of invasive electroencephalography in epilepsy surgery.

The authors compared the localization accuracy of interictal magnetoencephalography (MEG) with ictal and interictal invasive video electroencephalography (VEEG) in identifying the epileptogenic zone in epilepsy surgery candidates. Forty-one patients, 29 with temporal lobe epilepsy (TLE) and 12 with extratemporal lobe epilepsy (ETLE), participated. Only patients with interictal changes during the MEG recordings were included. A comparison of the accuracy of invasive VEEG and MEG seizure zone identification was based on the degree of overlap between the location of the actual surgical resection and the zone identified by each method, and the success of surgery in reducing seizure activity. No statistical differences were observed between the accuracy of invasive VEEG and MEG in determining the location of the seizure zone across TLE and ETLE cases. Invasive VEEG and MEG localization judgments were correct in 54% and 56% of the cases, respectively. Separate group analyses suggested that MEG may be less beneficial relative to invasive VEEG in ETLE than TLE cases. MEG is of statistically equivalent accuracy to invasive VEEG, despite the fact that its use has not reached optimal conditions. The authors predict the replacement of the more invasive procedure with MEG in the near future for TLE cases, subsequent to the optimization of the conditions under which preoperative MEG is performed.

Atypical language representation in patients with chronic seizure disorder and achievement deficits with magnetoencephalography.

PURPOSE: To characterize the relation between hemispheric asymmetries in language-specific brain activity and reading/spelling achievement by using magnetoencephalography (MEG). METHODS: Patients (n = 83) with medically intractable complex partial seizures of either left- or right-hemisphere origin were classified as having reading and/or spelling deficits (RS) or as not impaired (NI) by using standard achievement tests. All patients had undergone noninvasive functional mapping of receptive language cortex by using MEG as part of a preoperative seizure surgery evaluation. RESULTS: RS patients with left-hemisphere seizure onset exhibited relatively greater activation and earlier onset of late, language-specific MEG activity in posterior temporal and inferior parietal areas of the right as compared with the left hemisphere than did NI patients. These findings also were evident on an individual basis and were independent of global intellectual abilities. CONCLUSIONS: Reading and spelling achievement deficits in patients with complex partial seizures of left-hemisphere origin are associated with atypical language organization, possibly secondary to reorganization of language function to right-hemisphere areas that are not as efficient as homotopic areas in the left hemisphere in supporting reading and spelling functions.

Frequency of panic symptoms in psychogenic nonepileptic seizures.

This study investigates the frequency of symptoms of panic attack in a sample of adults (n = 18) and adolescents (n = 21) who were evaluated for intractable seizure disorder and diagnosed with psychogenic nonepileptic seizures (PNES). Medical records were retrospectively reviewed for symptoms associated with their typical seizure events as documented by the attending epileptologist. Adolescents, as a group, reported significantly more symptoms of panic attack than adults. Three adolescents met the full criteria for a panic attack, while no adults met these criteria. In addition, while numerous adults endorsed no panic symptoms associated with their PNES episodes, all adolescents endorsed at least one symptom. Implications of results are discussed in terms of the diagnosis and treatment of PNES in the different age groups.

Spatiotemporal patterns of language-specific brain activity in patients with chronic aphasia after stroke using magnetoencephalography.

Six participants with chronic aphasia secondary to first-ever ischemic stroke within the middle cerebral artery (MCA) distribution of the left hemisphere and six neurologically intact controls of similar age were given a running recognition memory task for words while the magnetic flux normal to the scalp surface was measured with a whole-head neuromagnetometer. This task had been previously shown to be valid for the localization and lateralization of brain activity specific to receptive language function. As expected, patients exhibited relatively decreased activation in areas known to be involved in receptive language function, including superior temporal gyrus (STG) in the left hemisphere, as well as increased activation of areas outside of the left STG that might potentially support language function. Decreased activation within left STG was associated with a reduction in receptive language in patients, as was increased activation outside of left STG. Results support hypotheses suggesting that peri-lesional areas outside premorbid language areas may assume receptive language function after aphasia secondary to stroke, but that better recovery occurs when putative premorbid language areas are able to normalize.

Magnetoencephalography (MEG) and magnetic source imaging (MSI).

BACKGROUND: Real-time, direct assessment of brain electrophysiology is critical for noninvasive functional mapping and for the identification of paroxysmal epileptiform abnormalities in the evaluation of patients for epilepsy surgery. Historically, electroencephalography (EEG) and evoked potentials (EPs) have performed these functions. However, both often required direct intracranial recording for precise localization. Magnetoencephalography (MEG) takes advantage of the fact that neuromagnetic signals penetrate the skull and scalp without distortion. The magnetic source image (MSI) is created when the MEG data is superimposed on a magnetic resonance image (MRI). REVIEW SUMMARY: MEG performs noninvasive functional imaging by recording the magnetic flux on the head surface associated with electrical currents in activated sets of neurons. MEG has rapidly evolved in the last 2 decades because of the introduction of whole head systems and advances in computer technology. MEG is now the imaging modality of choice where a precise and high degree of localization is required. MEG can be used to localize the primary sensory cortices (visual, auditory, or somatosensory), areas involved with receptive language function, the irritative zone in epilepsy patients, and identify children with anomalous language development. This article reviews the basis of MEG, the instrumentation used, the clinical applications and current limits of the technology. CONCLUSION: MEG studies can now be performed on a routine basis as a clinical tool. MEG is now indicated for: 1) localization of the irritative zone in lesional and nonlesional epilepsy surgery patients, 2) functional mapping of eloquent cortex, and 3) assessment of normal and abnormal language development. In the future MEG may help the understanding of normal development and reorganization after brain injury. The neurologist can use MEG data to complement structural and metabolic imaging techniques.

Categorical perception of speech stimuli in children at risk for reading difficulty.

Children determined to be at risk (n = 24) or not at risk (n = 13) for reading difficulty listened to tokens from a voice onset time (VOT) (/ga/-/ka/) or tone series played in a continuous unbroken rhythm. Changes between tokens occurred at random intervals and children were asked to press a button as soon as they detected a change. For the VOT series, at-risk children were less sensitive than not-at-risk children to changes between tokens that crossed the phonetic boundary. Maps of group stimulus space produced using multidimensional scaling of reaction times for the VOT series indicated that at-risk children may attend less to the phonological information available in the speech stimuli and more to subtle acoustic differences between phonetically similar stimuli than not-at-risk children. Better phonological processing was associated with greater sensitivity to changes between VOT tokens that crossed the phonetic boundary and greater relative weighting of the phonological compared to the acoustic dimension across both groups.