Andrew C. Papanicolaou

Dyslexia-specific brain activation profile becomes normal following successful remedial training

Objectives To examine changes in the spatiotemporal brain activation profiles associated with successful completion of an intensive intervention program in individual dyslexic children. Methods The authors obtained magnetic source imaging scans during a pseudoword reading task from eight children (7 to 17 years old) before and after 80 hours of intensive remedial instruction. All children were initially diagnosed with dyslexia, marked by severe difficulties in word recognition and phonologic processing. Eight children who never experienced reading problems were also tested on two occasions separated by a 2-month interval. Results Before intervention, all children with dyslexia showed distinctly aberrant activation profiles featuring little or no activation of the posterior portion of the superior temporal gyrus (STGp), an area normally involved in phonologic processing, and increased activation of the corresponding right hemisphere area. After intervention that produced significant improvement in reading skills, activity in the left STGp increased by several orders of magnitude in every participant. No systematic changes were obtained in the activation profiles of the children without dyslexia as a function of time. Conclusions These findings suggest that the deficit in functional brain organization underlying dyslexia can be reversed after sufficiently intense intervention lasting as little as 2 months, and are consistent with current proposals that reading difficulties in many children represent a variation of normal development that can be altered by intensive intervention.

A Comparison of Magnetoencephalography, MRI, and V-EEG in Patients Evaluated for Epilepsy Surgery

Summary: Purpose: To determine the efficacy and relative contribution of several diagnostic methods [ictal and interictal scalp and intracranial EEG, magnetic resonance imaging (MRI), and magnetoencephalography (MEG)] in identifying the epileptogenic zone for resection.

Source localization of the N400 response in a sentence-reading paradigm using evoked magnetic fields and magnetic resonance imaging

The aim of the present investigation was to localize the sources of the N400 response elicited in a sentence-reading paradigm. Eight neurologically healthy adults viewed sentences that were presented one word at a time in the center of a computer screen. Half of the sentences ended with a semantically inappropriate word, while the other half had appropriate endings. Event-related potentials recorded at Fz and Pz showed a negative-going deflection, the amplitude of which was strongly affected by semantic congruity (N400). Evoked magnetic fields that were simultaneously recorded over the left hemisphere showed clear magnetic field extrema in seven subjects during the time course of the N400. Underlying sources were successfully modeled as single equivalent current dipoles. Anatomical regions that contained the dipoles were localized by superimposing dipole coordinates onto magnetic resonance scans. Dipole regions were found in temporal lobe structures, in the vicinity of the hippocampus and the parahippocampal gyrus (in two subjects) and in posterior temporal neocortical regions (in the vicinity of the middle temporal gyrus; in five subjects). These findings are consistent with the view that posterior association cortices in the left hemisphere are involved in word recognition and semantic comprehension during reading.

Language dominance determined by magnetic source imaging A comparison with the Wada procedure

Objective: To evaluate the validity of data derived from magnetic source imaging (MSI) regarding cerebral dominance for language in patients with intractable seizure disorder.Method:— The authors performed functional imaging of the receptive language cortex using a whole-head neuromagnetometer in 26 consecutive epilepsy patients who also underwent the intracarotid amobarbital (Wada) procedure. During MSI recordings, patients engaged in a word recognition task. This task was shown previously to activate language areas in normal adults as well as in patients who undergo intraoperative language mapping, allowing confirmation of MSI findings. Language laterality indices were formed for both the Wada and the MSI procedures. In addition, clinical judgments regarding cerebral dominance for language were made using the two methods by independent raters. Results: Cluster analysis indicated excellent agreement between the quantitative MSI and Wada indices. Rater judgments showed almost complete agreement as well. Conclusion: MSI is a promising method for determining cerebral dominance for language.

Electric source localization of the auditory P300 agrees with magnetic source localization

The event-related cortical potential elicited in the context of auditory target detection tasks includes the N1, P2 and P3 components. The aim of the present study was to identify the sources of these scalp-recorded components using an electrical multiple dipole model. Nine healthy adults volunteered for the study. An auditory oddball paradigm was used. Stimuli (18% target and 82% non-target tones) were delivered through ear-phones and subjects were required to silently count the targets. Event-related potentials (ERPs) to these stimuli were recorded by 30 electrodes placed on the scalp. The identification of the sources of the ERP was attempted using the brain electric source analysis (BESA) program. The instantaneous source locations of N1, P2 and P3 reported in magnetoencephalographic (MEG) literature were used as initial starting locations for the spatio-temporal multiple dipole modeling of the EEG data. First the auditory long latency responses were modeled separately. Bilateral superior temporal plane sources with almost vertical orientations explained the first 250 msec window of the non-target tone recording including N1/P2 complex. This agrees with MEG source localization of N1m/P2m. Two slightly deeper dipoles in superior temporal gyri and bilateral dipoles in hippocampi or parahippocampal areas explained P3 (analysis window 250-600 msec). The final model explained the complete epoch of 600 msec with 6 dipoles and the residual variances of individual models ranged from 3.83% to 7.77%. The concordance between MEG and BESA source localization results supports the notion of generators in temporal lobes for the N1/P2 complex and generators in temporal and hippocampal areas for the P3 component.

Development and Aging of the Healthy Human Brain Uncinate Fasciculus across the Lifespan using Diffusion Tensor Tractography

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subjects intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

Does magnetoencephalography add to scalp video-EEG as a diagnostic tool in epilepsy surgery?

Objective: The authors evaluated the sensitivity and selectivity of interictal magnetoencephalography (MEG) versus prolonged ictal and interictal scalp video-electroencephalography (V-EEG) in order to identify patient groups that would benefit from preoperative MEG testing. Methods: The authors evaluated 113 consecutive patients with medically refractory epilepsy who underwent surgery. The epileptogenic region predicted by interictal and ictal V-EEG and MEG was defined in relation to the resected area as perfectly overlapping with the resected area, partially overlapping, or nonoverlapping. Results: The sensitivity of a 30-minute interictal MEG study for detecting clinically significant epileptiform activity was 79.2%. Using MEG, we were able to localize the resected region in a greater proportion of patients (72.3%) than with noninvasive V-EEG (40%). MEG contributed to the localization of the resected region in 58.8% of the patients with a nonlocalizing V-EEG study and 72.8% of the patients for whom V-EEG only partially identified the resected zone. Overall, MEG and V-EEG results were equivalent in 32.3% of the cases, and additional localization information was obtained using MEG in 40% of the patients. Conclusion: MEG is most useful for presurgical planning in patients who have either partially or nonlocalizing V-EEG results.

Diffusion tensor tractography quantification of the human corpus callosum fiber pathways across the lifespan

Several anatomical attributes of the human corpus callosum (CC) including the midsagittal cross-sectional area, thickness, and volume, have been used to assess CC integrity. We extended our previous lifespan quantitative diffusion tensor imaging (DTI) study of the regional CC midsagittal areas to include the CC volumes obtained from DTI fiber tracking. In addition to the entire CC tracked subvolumes we normalized volume with respect to each subjects intracranial volume (ICV) and the corresponding DTI metrics of the different specialized fiber pathways of the CC on a cohort of 99 right-handed children and adults aged 7-59 years. Results indicated that the CC absolute volume, the normalized volume fraction, and the fractional anisotropy followed inverted U-shaped curves, while the radial diffusivities followed a U-shaped curve reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood. Our study provides for the first time normative baseline macro- and microstructural age trajectories of the human CC subvolumes across the lifespan that can be helpful for normative behavioral and clinical studies.

Brain mechanisms for reading : the role of the superior temporal gyrus in word and pseudoword naming

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.

Multiple Bilaterally Asymmetric Cortical Sources Account for the Auditory N1m Component

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.