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Noninvasive functional brain imaging with magnetoencephalography (MEG) is regularly used to map the eloquent cortex associated with somatosensory, motor, auditory, visual, and language processing before a surgical resection to determine if the functional areas have been reorganized. Most tasks can also be performed in the pediatric population. To acquire an optimal MEG study for any of these modalities, the patient needs to be well rested and attending to the stimulation.

AbstractIn the present study, a novel data-driven topological filtering technique is introduced to derive the backbone of functional brain networks relying on orthogonal minimal spanning trees (OMSTs). The method aims to identify the essential functional connections to ensure optimal information flow via the objective criterion of global efficiency minus the cost of surviving connections. The OMST technique was applied to multichannel, resting-state neuromagnetic recordings from four groups of participants: healthy adults (n= 50), adults who have suffered mild traumatic brain injury (n= 30), typically developing children (n= 27), and reading-disabled children (n= 25). Weighted interactions between network nodes (sensors) were computed using an integrated approach of dominant intrinsic coupling modes based on two alternative metrics (symbolic mutual information and phase lag index), resulting in excellent discrimination of individual cases according to their group membership. Classification results using OMST-derived functional networks were clearly superior to results using either relative power spectrum features or functional networks derived through the conventional minimal spanning tree algorithm.

In this study, we have addressed the question of functional brain reorganization for language in the presence and absence of anatomical lesions in two patients with epilepsy using cortical stimulation mapping and high gamma (HG) activity in subdural grid recordings. In both, the expressive language cortex was defined as the cortical patch below the electrode(s) that when stimulated resulted in speech arrest, and during speech expression tasks generated HG activity. This patch fell within the borders of Broca’s area, as defined anatomically, in the case of the patient with a lesion, but outside that area in the other, lesion-free patient. Such results highlight the necessity for presurgical language mapping in all cases of surgery involving the language-dominant hemisphere and suggest that HG activity during expressive language tasks can be informative and helpful in conjunction with cortical stimulation mapping for expressive language mapping.

Non-invasive functional evaluation of the brain complements structural MRI imaging and has largely supplanted invasive techniques such as awake craniotomy. Techniques used for functional mapping of the brain include BOLD-functional MRI (fMRI), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). We describe the case of a right-handed patient with a lesion centered in the left inferior perirolandic cortex who underwent fMRI, MEG, and TMS on a single day to facilitate maximal lesion resection while preserving eloquent cortex and eloquent white matter tracts.

ABSTRACT.Magnetoencephalography (MEG) measures the field generated by the brain's electrical currents noninvasively. MEG is currently used for localization of epileptiform activity sources and for presurgical functional brain mapping. Such mapping with MEG requires the patients to be cooperative and lie still on their back for as long as ten minutes at a time. Hence, acquiring successful MEG in very young children, developmentally delayed individuals, and patients with skeletal abnormalities proves to be a challenge. Over the past several years, our group has undertaken research aimed at the effective use of sedation during MEG to identify epileptogenic areas and perform functional brain mapping in very young or developmentally delayed individuals. We summarize our experience of MEG data acquisition with sedation and demonstrate that epileptogenic areas can be identified and functional brain mapping can be successfully performed under sedation with propofol.

AbstractThe impact of the posterior callosal anomalies associated with spina bifida on interhemispheric cortical connectivity is studied using a method for estimating cortical multivariable autoregressive models from scalp magnetoencephalography data. Interhemispheric effective and functional connectivity, measured using conditional Granger causality and coherence, respectively, is determined for the anterior and posterior cortical regions in a population of five spina bifida and five control subjects during a resting eyes-closed state. The estimated connectivity is shown to be consistent over the randomly selected subsets of the data for each subject. The posterior interhemispheric effective and functional connectivity and cortical power are significantly lower in the spina bifida group, a result that is consistent with posterior callosal anomalies. The anterior interhemispheric effective and functional connectivity are elevated in the spina bifida group, a result that may reflect compensatory mechanisms. In contrast, the intrahemispheric effective connectivity is comparable in the two groups. The differences between the spina bifida and control groups are most significant in the θ and α bands.

In contrast to word-level skills, the neural basis of sentence comprehension in children with reading difficulties is not well understood. Using magnetic source imaging, we investigated the spatiotemporal dynamics of regional activity associated with silent passage reading in nonimpaired and students with reading difficulties. The latter exhibited underactivation of the temporoparietal and visual cortices, bilaterally, and of the left posterior cingulate region. Late activity in left temporoparietal and ventral occipitotemporal regions was found to be a significant predictor of individual reading ability in nonimpaired, but not in students with reading difficulties. These findings support the notion that reduced temporoparietal activation during word reading in context, is a hallmark of the functional deficit in reading disability.

The neural origins of the cortical response to rare sensory events remain poorly understood. Using simultaneous event-related potentials and magnetic resonance imaging, we investigated the anatomical profile of regional activity at various processing stages during performance of auditory and visual variants of an oddball paradigm. The earliest rarity-detection response was found in sensory-specific cortices, rapidly spreading to tertiary association areas, mesial temporal and frontal cortices by 150–200 ms. P3m-related activity was not found in sensory-specific cortices. On the basis of the anatomic distribution of P3m-related activity, this component is likely to reflect more generalized cognitive abilities hosted by association cortical regions.

One of the key ideas regarding atypical connectivity in autistic brains is the hypothesis of noisier networks. The systems level version of this hypothesis predicts reduced reliability or increased variability in the evoked responses of individuals with autism. Using magnetoencephalography, we examined the response of individuals with autism spectrum disorder versus matched typically developing persons to passive tactile stimulation of the thumb and index finger of the dominant (right) hand. A number of different analyses failed to show higher variability in the evoked response to the thumb or to the index finger in the autism group as compared with typicals. Our results argue against the hypothesis that the brain networks in autism are noisier than normal.

We studied the relation between cortical oscillatory rhythms and the structural integrity of the corpus callosum in 21 children with spina bifida and hydrocephalus. Participants underwent resting state neuromagnetic recordings and diffusion tensor imaging. Areas of three segments of the corpus callosum (genu, body, splenium) were derived through diffusion tensor imaging-based morphometrics. Children with spina bifida showed reduced values of spectral power in the , and bands when compared with age-matched controls, but only in the posterior and temporal regions. Reduced spectral power in posterior regions correlated with decreased area of the posterior segments of the corpus callosum. Atypical cortical oscillatory activity is associated with reduced transcallosal connectivity in children with spina bifida.

The comorbidity of ‘core characteristics’ and sensorimotor abnormalities in autism implies abnormalities in brain development of a general and pervasive nature and atypical organization of sensory cortex. By using magnetoencephalography, we examined the cortical response to passive tactile stimulation of the thumb and index finger of the dominant hand and lip of the individuals with autism spectrum disorder and typically developing persons. The distance between the cortical representations of thumb and the lip was significantly larger in the autism group than in typicals. Moreover, in cortex, the thumb is typically closer to the lip than the index finger. This was not observed in persons with autism. Our findings are arguably the first demonstration of abnormality in sensory organization in the brains of persons with autism.

Inconsistent differences in the corpus callosum (CC) structure between dyslexic readers (DRs) and typical readers (TRs) have been reported. We examine differences in CC splenium microstructure and the association of splenium microstructure with reading-related skills. Nine DRs and 18 TRs completed a reading skills battery and diffusion tensor imaging. DRs had higher splenium fractional anisotropy (FA) and axial diffusivity (LA) as compared with TRs. Retrieval of orthographic information from the language lexicon was negatively associated with FA and LA within both reading groups. Phonological awareness was positively associated with splenium FA and LA in TRs but not DRs. This study suggests two white matter pathways that may be differentially associated with reading skills in the CC splenium.

We used a diffusion tensor imaging-based whole-brain tissue segmentation to characterize age-related changes in (a) whole-brain grey matter, white matter, and cerebrospinal fluid relative to intracranial volume and (b) the corresponding brain tissue microstructure using measures of diffusion tensor anisotropy and mean diffusivity. The sample, a healthy cohort of 119 right-handed males and females aged 7–68 years. Our results demonstrate that white matter and grey matter volumes and their corresponding diffusion tensor anisotropy and mean diffusivity follow nonlinear trajectories with advancing age. In contrast, cerebrospinal fluid volume increases linearly with age.

Magnetoencephalography (MEG) is a completely noninvasive method of functional imaging. MEG performs noninvasive functional imaging by recording the magnetic flux on the head surface associated with electrical currents in activated set of neurons, estimating the location of such sets, and projecting the location onto the MRI of the brain to identify and visualize the activated brain region. MEG has rapidly evolved in the last two decades due to 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. Ongoing studies show that it provides superior temporal and spatial resolution when compared to functional MRI. MEG is the only imaging technique that can reveal brain function over millisecond intervals. Magnetoencephalography was initially used to localize the primary sensory cortices, and depending on the nature of stimulus, this has been validated for visual, auditory or somatosensory areas. In order to localize brain networks involved during the engagement of cognitive tasks, both temporal and spatial resolution are critical. MEG is the only imaging technology capable of providing this information. We have successfully used magnetoencephalography to noninvasively localize brain areas involved with key language functions. These have been validated through the Wada procedure and with direct electrocortical stimulation. The utility of MEG in noninvasively localizing language function is reviewed. MEG also allows us to understand the differences in functional organization of the brain underlying the reading performances of dyslexic children. We have recently developed a protocol using magnetoencephalography to assess memory function (independent hippocampal activation). This is in the process of being validated by comparison with the Wada procedure. Antepartum knowledge of fetal health status is essential for early identification of fetal risk for injury or death. Most modern techniques monitor the fetal heart rate and use ultrasound to assess fetal movement. We propose that magnetoencephalography, with a new system design that provides good access to the fetal head, will allow assessment of fetal brain activity. Early results show that fetal auditory-evoked potentials can be recorded reliably. Magnetoencephalography has now been demonstrated to be capable of noninvasively mapping primary sensory functions, language function, and soon memory and other affective cognitive stimuli. Additionally, it appears as though this procedure can be extended to the fetus to allow assessment of fetal brain activity. As we continue to use magnetoencephalography to define the substrates for normal brain activity, we will be able to critically evaluate neurologic problems that interrupt or impair these functions. Hopefully, magnetoencephalography will allow early objective identification of these impairments and treatment protocols to be developed.

Recognition of words and kaleidoscope pictures showed a double dissociation of left and right hippocampal activity using magnetic source imaging (MSI). MSI has advantages over alternative imaging techniques that measure hemodynamic changes for identifying regional changes in brain activity in real time and on an individual subject basis without the need for image subtraction. In this study, lists of words or kaleidoscope pictures were presented for memorization followed by tests of list items and foils during which brain activity was recorded. There was greater activation in the left than the right hippocampus with abstract nouns (e.g., relief) and greater activation in the right than the left hippocampus with kaleidoscope pictures. This dissociation was evident on a case by case basis. This study demonstrates the specialization of the two medial temporal lobe (MTL) regions, including the hippocampi, for mnemonic processing of verbal and pictorial items that are difficult to encode verbally.

Word recall is facilitated when deep (e.g. semantic) processing is applied during encoding. This fact raises the question of the existence of specific brain mechanisms supporting different levels of information processing that can modulate incidental memory performance. In this study we obtained spatiotemporal brain activation profiles, using magnetic source imaging, from 10 adult volunteers as they performed a shallow (phonological) processing task and a deep (semantic) processing task. When phonological analysis of the word stimuli into their constituent phonemes was required, activation was largely restricted to the posterior portion of the left superior temporal gyrus (area 22). Conversely, when access to lexical/semantic representations was required, activation was found predominantly in the left middle temporal gyrus and medial temporal cortex. The differential engagement of each mechanism during word encoding was associated with dramatic changes in subsequent incidental memory performance.

The purpose of this study was to test the neurological validity of a dual-route model of reading by asking patients, who were undergoing electrocortical stimulation mapping, to read words with irregular print-to-sound correspondences and pseudowords. Brain activation profiles were also obtained from these patients during an auditory and a visual word recognition task using whole-head magnetic source imaging. We demonstrated that reading is subserved by at least two brain mechanisms that are anatomically dissociable. One mechanism subserves assembled phonology and depends on the activity of the posterior part of the left superior temporal gyrus (STGp), whereas the second is responsible for addressed phonology and does not necessarily involve this region. The contribution of STGp to reading appears to be based on its specialization for phonological analysis operations, involved in the processing of both spoken and written language.

The magnetic flux normal to the scalp surface was measured with a whole-head neuromagnetometer while right-handed subjects (N = 15) were engaged in either an auditory word- or a tone-recognition task. Sources of the recorded magnetic fields were modeled as equivalent current dipoles at 4 ms intervals and the number of sources in the later portion of the magnetic response was used as an index of the degree of brain activation. Significantly more sources were found in the left as compared to the right hemisphere in the word but not the tone task on a group basis. On an individual basis, 13/15 subjects had more sources in the left as compared to the right hemisphere during the word task, while in the tone task 3/10 subjects showed this pattern. Sources of activity were found in the left superior and middle temporal gyri in all subjects with available MRI scans. Sources were also found in the supramarginal gyrus and in medial temporal areas, including the hippocampus, in the majority of cases. MEG appears to be a promising tool for detecting activity in cerebral areas specialized for language and memory function.

The hypothesis that the N1, the major negative component of the cortical evoked response to auditory stimuli, originates from the primary auditory cortex has been supported by several studies. In a previous study we showed that, when monaural stimulation with pure tones is used, the distribution of the N1 peak over the scalp could be accounted for by successive activation of adjacent sources on the floor of the Sylvian fissure. In an attempt to establish the generality of the phenomenon, in this study we investigated further the generation of the N1 component using a variety of auditory stimuli, including pure tones, complex sounds (musical notes), and words, as well as binaural stimulus presentation. Additionally, we used a new recording system which allows recording of the distribution of the magnetic flux over the entire head simultaneously, thus eliminating the need for multiple recording sessions and the related problems of habituation and of changes in attention level. We found that a series of single dipolar sources could account for the entire duration of the N1m component. The location of the sources fell within the primary auditory cortex and, during the evolution of the component, they followed a posterior-anterior, medial-lateral, superior-inferior trajectory, bilaterally, along the superior surface of the temporal lobes. Additionally, the distribution of N1 sources on the two hemispheres showed a marked asymmetry, with the right hemisphere sources covering a larger area. The established consistency of successive source excitation across subjects, studies, types of stimuli, and recording systems, as well as the newly demonstrated hemispheric asymmetry of source extent, suggest the presence of a reliable phenomenon indicative of the functional organization of the auditory cortex.

FUNCTIONAL brain imaging techniques hold many promises as the methods of choice for identifying areas involved in the execution of language functions. The success of any of these techniques in fulfilling this goal depends upon their ability to produce maps of activated areas that overlap with those obtained through standard invasive procedures such as electrocortical stimulation. This need is particularly acute in cases where active areas are found outside of traditionally defined language areas. In the present report we present two patients who underwent mapping of receptive language areas preoperatively through magnetoencephalography (MEG) and intraoperatively through electrocortical stimulation. Language areas identified by both methods were located in temporoparietal regions as well as in less traditional regions (anterior portion of the superior temporal gyrus and basal temporal cortex). Importantly there was a perfect overlap between the two sets of maps. This clearly demonstrates the validity of MEG-derived maps for identifying cortical areas critically involved in receptive language functions.

• An evoked potentials procedure that has repeatedly provided evidence of predominant right-hemisphere engagement during language tasks in recovered adult aphasics was applied to the study of 14 children with early unilateral left-hemisphere lesions and in 14 matched normal subjects. In contrast with the adult patients, the children with left-hemisphere lesions displayed the normal pattern of predominant left-hemisphere engagement in language and right-hemisphere engagement in visuospatial tasks. These data suggest that language restitution and development following early lesions involves intrahemispheric rather than interhemispheric functional reorganization.

Having noticed a consistent activation of right frontal areas during several visuospatial tasks, we retrospectively examined data from 121 regional cerebral blood flow (rCBF) studies conducted under a variety of conditions involving different stimuli, response modes and task requirements. These were compared to scans conducted while subjects were at rest. Significant hemispheric differences were found for all tasks combined in the frontal regions, where right flow was greater than left, especially in more demanding tasks. This finding suggests a very general role for the right hemisphere in attention or vigilance.

Neuromagnetic measurements in the visual and somatosensory modalities reveal that, following repetitive stimulation, the brain persists in emitting synchronized after-discharges in the form of oscillations with highly specific spectral composition. In the visual modality, this rhythmic activity is centered at the frequency of the resting alpha rhythm and it is most readily induced by stimulation of the same frequency. This suggests that the phenomenon is due to synchronization of the generators responsible for the natural rhythms by the steady-state stimulation and that these generators behave as resonant oscillators. The phenomenon could then be referred to as Synchronized Spontaneous Activity (SSA). The discovery of this phenomenon has important implications for modelling the dynamics of normal evoked and spontaneous cerebral activity as well as for the understanding of pathological conditions such as photically induced epilepsies.

Auditory Evoked Magnetic Fields (EFs) to tonal stimuli were recorded at homotopic maxima over the left and right auditory areas in nine subjects. Recordings were made during two conditions, both involving simultaneous presentation of the probe tone stimuli and a set of tape-recorded verbal material. During the control condition subjects were instructed to attend to the tones and ignore the verbal material. In the phonological processing condition they were instructed to ignore the tones and attempt to identify a phonological target item which was embedded in the verbal material. EFs obtained during both conditions were characterized by an early N1m and a later P2m component corresponding to the N1 and P2 components of auditory evoked potentials (EPs). During the phonological condition, the amplitude of the N1m was significantly reduced in both hemispheres symmetrically whereas the amplitude of the P2m was attenuated to a significantly greater degree in the left hemisphere. These data are in agreement with previous EP evidence of greater interference of linguistic processing with processing of irrelevant probe stimuli in the left hemisphere, indicative of greater left hemisphere involvement in language tasks.

Alpha and beta content of spectrally analyzed EEG were used to assess differential hemispheric engagement during two linguistic tasks (semantic and phonetic) and one acoustic task involving detection of target items embeddded within the same stimulus series. Beta content of the EEG increased reliably in the left hemisphere during the linguistic tasks, whereas the expected attenuation or blocking of alpha did not occur reliably. These data suggest that left hemisphere beta enhancement rather than alpha blocking is a more efficient index of differential hemispheric engagement during language processing.

Short and long latency somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded over the contralateral hemisphere. Simultaneously, signals evoked by the same stimulus were monitored at Erb's point. Recordings were made during three conditions which were presented in a different random order to each of the subjects tested. During the control condition the subjects were instructed to attend to and count the number of electrical pulses delivered to the median nerve of their right hand. During the two task conditions, in addition to the pulses, the subjects received stimulation on the dorsal surface of one of their hands. This consisted in drawing circles lightly for the duration of SEP recording using a cotton swab (Q-tip). During the trial, the Q-tip was momentarily withdrawn 15 to 20 times and the subject's task was to ignore the pulses, attend to this cutaneous stimulation and count the number of times the cutaneous stimulation was interrupted. SEPs to the pulse were significantly greater in amplitude when cutaneous stimulation was delivered to the same hand as the pulse (the right hand) than when it was delivered to the left hand. This effect was confined to the long-latency SEPs and did not appear in either the Erb's point response or the short latency SEPs. These data indicate that selective attention to peripheral stimulation is a relatively late process mediated by cortical mechanisms and argue against the notion of early suppression of irrelevant stimulus channels in subcortical centers or in the periphery. Moreover, they indicate that in the specific case of limb stimulation, selection is based on physical channel (the hand) rather than the more subtle nature of the quality of information.

Evoked Potentials (EPs) to a click stimulus were recorded at the temporal areas of both hemispheres of dextral subjects engaged in covert rehearsal of a verbal passage or in covert rehearsal of musical passages. A pattern of left hemisphere attenuation of the click EPs was observed in all subjects during speech rehearsal but not during music rehearsal. The implications of these findings for the issue of electroencephalographic localization of speech production mechanisms in the left hemisphere are discussed.

Evoked potentials (EPs) to a probe tone stimulus were recorded simultaneously at the temporal and parietal areas of the left and right hemisphere of dextral adults engaged in either an arithmetic or a visuospatial task. The probe EP amplitude was attenuated in the left temporal area during the arithmetic task and in the left temporal and both parietal areas, but significantly more in the right, during the visuospatial task, indicating distinct patterns of regional cerebral engagement for the two types of cognitive activity.

THE purpose of this study was to extend previous findings of changes in magnetic flux amplitude associated with neuronal currents in the human auditory cortex in response to two-tone stimuli selected from a tone-onset time (TOT) continuum. The results replicated previous findings byindicating a close correspondence between N1m field strength functions and individual perceptual identification curves. In a second experiment event-related fields were recorded in response to two-tone stimuli in which the two sinusoid components always started simultaneously, yet they showed the same energy envelope as the TOT stimuli (amplitude modulated (AM) tokens). The results showed that N1m modulation as a function of TOT could not be accounted for by an effect of AM. The findings suggest that discontinuities in N1m field amplitudefunctions were the result of interactions between two populations of active neurons each displaying distinct average sound frequencypreferences.

Normal volunteers underwent three successive scans of regional cerebral blood flow (rCBF) using the 133Xe inhalation technique during visual stimulation, a recognition memory task and a resting state defined by high EEG alpha content. Since the stimulation was virtually identical in both non-rest conditions, we were able to separate the CBF pattern resulting from simple stimulation and that resulting from the cognitive (recognition memory) component alone. These turned out to have very nearly opposite effects on the normal anterior-to-posterior resting state gradient: the sensory component diminished the gradient, while the cognitive component exaggerated it. It is suggested that these normative data can be of clinical value in the study of cerebral recovery/reorganization following post-traumatic amnesia.

Since the dichotic listening technique was first described (Broadbent, 1954; Kimura, 1961), researchers have been interested in its ability to document hemispheric dominance for language and other functions in a noninvasive fashion. Numerous articles have been published using normal healthy subjects as well as others using patients who have suffered neurological disease or damage. Much controversy has been generated over the use of dichotic listening in the latter population, however, since unilateral brain lesions might be expected to alter normal perception. This paper responds to one recently published by Niccum and Speaks (1991) that attempted to explain why a lesion effect, and not hemispheric reorganization, is the best explanation for findings of left-ear advantage in recovering aphasics.

A dichotic-listening procedure was used to investigate the role of the right hemisphere in recovery from aphasia following left-hemisphere stroke. Thirtyone stroke patients were divided into three groups: (a) patients who were recovering from aphasia (Aphasic group, n=11), (b) patients who had experienced mild strokes with only transient dysarthria (Dysarthric group, n=10), and (c) patients who had sustained right-hemisphere stroke with no language disturbance (Nonaphasic group, n=10). In addition, a group of normal, healthy volunteers served as a control group (n=11). Results show that, like the Control subjects, the Dysarthrics and Nonaphasics showed a strong right-ear advantage (REA) for dichotically presented consonant-vowel (CV) syllables. This is usually thought to be an indication of left-hemisphere dominance (Kimura, 1961). By contrast, the Aphasic group showed left-ear advantage (LEA) suggesting a shift in cerebral dominance for language. The possibility that the results were due to sensory degradation of the auditory messages (lesion effect) was explored. This idea was rejected in favor of an explanation based on increased right-hemisphere mediation of language following left-hemisphere aphasiogenic lesions.

The question whether stimuli forming temporal patterns are processed differently from identical stimuli belonging to irregular temporal aggregates was investigated. Tones forming either regular or irregular triads were presented to eight normal subjects. The N1-P2 amplitude of evoked potentials to tones forming temporal patterns were consistently lower than those to tones in the irregular aggregates. These data indicate that the perceptual phenomenon of subordination of constituent parts to a well-formed whole is demonstrable in electrophysiological terms.

We used magnetoencephalography (MEG) to assess the degree of hemispheric activation in eleven normal, right-handed subjects with no history of neurological disorder or learning disability during performance of a word- and a face-recognition tasks. Neuromagnetic activity was recorded using a whole-head system, and the sources of the recorded magnetic fields were modeled as single equivalent current dipoles. Early (<200 msec) cerebral activation, defined by the number of dipoles identified by the data-fitting algorithm, was localized in the occipital cortex during both tasks, as expected. During the language task, the extent of the later (>200 msec) cerebral activation was approximately double in the left hemisphere in almost all subjects, involving temporal and temporoparietal areas. In contrast, during the face-recognition task, the corresponding activation was mostly symmetrical across the two occipital lobes, also involving the posterior-inferior aspect of the right temporal lobe. Our results suggest that the MEG is a suitable method of assessing noninvasively hemispheric specialization for language.

Summary In this study we attempted to extend our previous results on regional specialization of frontal cortical function in humans, by means of magnetoencephalography (MEG). We used a verbal task and predicted that some part of the left frontal lobe would be active during engagement in that task, since the left hemisphere is known to be implicated in language. We did not require a motor response because in previous experiments we observed bilateral frontal magnetic activity, and we suspected that it was due to the addition of movement-related fields to our recordings. Six right handed subjects (three males and three females) participated in the study. The task consisted in silently counting the number of word pairs that matched with respect to semantic category. Experimental runs were composed by series of 120 trials or word pairs. All six subjects presented dipolar magnetic field distributions on the left fronto-temporal area of the scalp, but not on the right, during different portions of the trial duration. These fields were successfully modeled as equivalent current dipoles (ECDs). The spatial ECD coordinates were translated onto magnetic resonance image (MRI) coordinates for each subject. The dipole positions were typically near the cortical surface corresponding to areas 6 and 44 of Brodmann. No dipole-like sources were observed in the right frontal lobe.

Summary Previous studies have demonstrated that externally measured magnetic field patterns are indicative of activity in the vicinity of the right hippocampal formation during infrequent and unpredictable intrusions or omissions of visual stimuli in an oddball evoked response paradigm. These fields occur coincident with late endogenous evoked potential components that are consistently recorded in similar situations. In the present study, magnetic fields temporally corresponding to the late P300 component of simultaneously recorded evoked potentials were accounted for by sources in the vicinity of the left and right hippocampus in addition to previously reported sources in the vicinity of the primary visual cortex. Projection of these sources onto MRIs suggested that both hippocampal structures are simultaneously active and that there is an amplitude and strength-related dominance of the right hippocampal sources to visual stimulation.

Summary The replicability of dipole localizations between sessions in an unselected group of subjects was studied. Auditory evoked magnetic fields (AEMFs) in response to contralaterally and ipsilaterally presented 1 kHz tone bursts were recorded from the right hemisphere of 12 subjects with normal hearing in two replicate sessions several days apart. Three long-latency components of the AEMF were studied, occurring at latencies near 50 msec (P1m), near 100 msec (N1m) and near 165 msec (P2m). A spherical model of the head was used to fit equivalent-current dipoles to the data. Statistical analysis of dipole parameters revealed virtually no differences between the two testing sessions. The variability between sessions had a mean absolute difference of 3 to 10 mm for the spatial parameters. Comparison of dipole parameters between components showed that there was a replicable, but nonsignificant, trend for a difference in the location of the N1m from contralateral vs. ipsilateral stimulation, and a statistically significant confirmation that the P2m is located anterior to the N1m for contralateral stimulation. Magnetic resonance images from each subject were used to locate the dipoles near the primary auditory cortex in the Sylvian fissure.

Memory assessment is one of the principal objectives of neuropsychological evaluation. Yet, careful examination reveals very clear shortcomings in the memory tests employed by neuropsychologists. Specifically, most procedures are selected on the basis of their ability to detect structural brain pathology rather than their ability to assess memory performance per se or the constituent operations that underlie it. This paper addresses the shortcomings in the structure of several representative memory tests in neuropsychology, how some of these limitations have been overcome with newer scales, and presents practical and theoretical considerations for the development of new clinical memory measures.

Sixty patients with temporal lobe epilepsy were classified into reading deficient (RD; n =21) and non-reading deficient (non-RD; n =39) groups. Selective deficits in verbal or nonverbal memory, consistent with side of seizure onset, were evident in the non-RD patients. Both verbal and nonverbal memory performance were reduced equivalently in individuals with RD, regardless of side of seizure onset. As a result, memory tests that were accurate in identifying side of seizure onset in the non-RD group were not as accurate in the RD group. When individual cases were classified using a clinically applicable decision rule, significantly more RD patients were either unclassifiable or incorrectly classified than were non-RD patients. Findings suggest that preoperative memory data obtained from individuals with epilepsy and evidence of RD may not be as valid an indicator of side of seizure onset as are those obtained from patients without RD.

As part of a multi center, collaborative project, response to fenfluramine was assessed in 10 autistic outpatients. After 4 months of treatment, blood serotonin concentrations decreased an average of 60 per cent and returned to pretreatment levels after 2 months on placebo. This reduction was accompanied by a decrease in certain behavioral symptoms, including motor activity, distractibility, and mood disturbances. Baseline evoked potential recordings indicated that autistic patients tended to have a larger amplitude of the P3 component to frequent tones as compared to age-matched controls. A tendency toward “normalization” of the P3 effect was observed during the medication trial and during the final placebo period. Treatment response was not related to initial serotonin levels, and no major clinical side effects were associated with fenfluramine.

• Magnetoencephalography offers the possibility of localizing accurately and noninvasively the source of intracranial currents associated with normal and abnormal brain activity. The purpose of this study was to assess the validity and across-subject reliability of localization of cortical sources responding to ipsilateral and contralateral auditory stimulation. Magnetic evoked fields to both stimulation conditions were measured in eight consecutive normal subjects, and the cortical sources of these fields were estimated on the basis of these measurements. Subsequent projection of the source location coordinates onto magnetic resonance images showed that in all subjects the sources were accurately estimated to fall in the vicinity of the auditory cortex and that two separate sources may account for the response to ipsilateral and contralateral stimulation.

• Cortical evoked potentials and dichotic listening test scores were used to assess the extent of activation of the two cerebral hemispheres during various language tasks in a group of 21 recovering aphasics, 15 nonaphasic patients with right-hemisphere stroke, and 17 normal volunteers. In agreement with previous findings, both measures suggest greater right-hemisphere activation during language processing in the recovering aphasics than in nonaphasic patients and normal subjects. These data support the view that restitution of language entails reorganization of brain function with increased participation of the nondominant hemisphere.

• A probe evoked potentials procedure was used to assess the relative engagement of both cerebral hemispheres during a language task in the following four groups of dextral adults: left hemisphere (LH)—damaged aphasics recovering from stroke, dysarthrics, right hemisphere (RH)—damaged nonaphasic patients, and normal control subjects. In agreement with previous findings using the probe procedure, the present results indicate greater task-specific RH activation in recovering aphasics and, to a lesser degree, dysarthric patients and greater LH activation in both nonaphasic, RH-damaged patients and normal control subjects. On the basis of these data, we suggest that increasing participation of the nondominant hemisphere may subserve restitution of language in adults sustaining LH lesions.

Utilizing the high spatial and temporal resolution of magnetoencephalography in conjunction with magnetic resonance images, the current study explored the underlying electrical patterns of cortical excitation during both contralateral and ipsilateral auditory stimulation. Instead of studying only the peaks of the N100 component of the evoked magnetic field, a 30-msec window was chosen about the area where the peaks occurred and the intracranial sources generating that component were estimated at successive 5-msec intervals. Results indicated that the sources for both contralateral and ipsilateral conditions were best represented as a continuous movement of activation in an anterior–inferior direction along the superior surface of the temporal lobe. Although the peak magnetic fields of the N100 to contralateral stimulation were of shorter latency and higher amplitude, the generating sources of both had very similar time-dependent movement patterns, and comparisons of source localizations were dependent on the latency at which they were contrasted.

Evoked potentials (EPs) to a monaurally presented probe stimulus were recorded from the vertex in subjects engaged in shadowing a word list presented simultaneously to the contralateral ear. Greater attenuation of the N1-P2 and baseline-P2 amplitude of the probe EPs was observed when the probe stimulus was presented to the right ear and the verbal material presented to the left ear than when the opposite stimulation arrangement was used. The baseline-N1 amplitude, however, was equally attenuated during the two stimulation arrangements. The implications of these findings for the issue of differential, task-specific attenuation of probe EPs are discussed.

The probe evoked potentials method which involves recording brain responses to irrelevant stimuli during performance of a wide range of cognitive tasks, is used with increasing frequency to assess patterns of regional cerebral activation mediating distinct cognitive operations. This paper delineates the evolution of the method, describes its procedural and theoretical features, reviews its applications with normal adults, infants and children, and with neuropsychologically compromised individuals. The outcome of these studies points to the advantages of this method over traditional evoked potential procedures in the assessment of regional cerebral engagement in cognitive operations, free of confoundings due to stimulus and response-specific activity, in ecologically valid experimental situations.

Two evoked potential (EP) techniques and the selective reminding test were employed to investigate an apparently benign forgetfulness in seven elderly subjects and seven age-matched elderly subjects with normal memory. EPs were also recorded in a group of seven young adults. Latency of the P3 component, which has been demonstrated to increase in primary degenerative dementia, displayed the normal age-related variation in both elderly groups, but did not differ between the forgetful subjects and the elderly controls. Further, no difference in the recovery cycle of the EP, as measured in a two tone stimulation paradigm, was present between forgetful and elderly control groups. Reexamination of memory after nearly a year disclosed no evidence of deterioration in either elderly group. These findings suggest that senescent forgetfulness, as defined herein, may be a nonprogressive memory disorder.

The American Academy of Neurology (AAN) endorsement for the use of fMRI evaluation of hemispheric dominance for language in epilepsy surgery candidates1appears as an odd and disconcerting sequel to the article by Eckland et al.,2which reported that the clustering approach in functional MRI (fMRI) data processing may be responsible for an excessively high rate of false-positive findings. The latter report implied that up to 70% of the significant fMRI effects reported in approximately 40,000 peer-reviewed publications could represent no brain physiology facts, but type I statistical errors to the degree that they employed clustering of activated voxels.2Consequently, it is fitting to suggest users of these popular fMRI software packages (SPM, FSL, AFNI) reconsider conclusions based on differences in activation levels of voxel clusters between task conditions. This raises the question of whether those who use the clustering procedure for the purpose of assessing hemisphere dominance for language should be alarmed for having made incorrect assessments in the past and refrain from using them for the same purpose in the future. Our answer is no, since language laterality judgments are typically made on the basis of laterality indices (i.e., the relative degree of activation defined as the ratio of left- and right-hemisphere activated voxels that are equally likely or unlikely to be activated). However, depending on how users of these automated software packages derive estimates of localization of the language network hubs (a practice not endorsed by the AAN),1they may need to exercise more caution now that the shortcomings of these data reduction and analysis procedures were directly demonstrated and made widely known.