The Neural Correlates of Impaired Self-Monitoring Among Individuals With Neurodegenerative Dementias.

OBJECTIVE: Self-monitoring is a crucial component of human empathy and necessary for the formation and repair of social relations. Several studies have brought to light possible neuronal substrates associated with self-monitoring, but the information that they have provided is inconclusive. The authors, therefore, studied a large group of patients with dementia to assess what brain structures are necessary for the self-monitoring function.Methods: Seventy-seven patients with dementia of various types were screened using voxel-based morphometry to assess possible volume reduction in the brain structures of patients with self-monitoring problems, and the decrease of socioemotional expressiveness and modification of self-presentation was estimated using the Revised Self-Monitoring Scale. Regression analysis was employed to investigate the correlation between gray matter loss and deficient self-monitoring.Results: The socioemotional expressiveness scores were associated with decreased gray matter volume in the right olfactory cortex, inferior frontal gyrus, superior temporal pole, parahippocampal gyrus, insula, and medial temporal gyrus bilaterally. Self-presentation scores were associated with bilateral gray matter volume reduction in the olfactory cortex, insula, rectus gyrus and inferior frontal gyrus, right superior temporal pole, and parahippocampal gyrus, as well as the left medial temporal gyrus and anterior superior frontal gyrus.Conclusions: These results suggest that patients with dementia present decreased ability of self-monitoring, probably due to impaired insula and orbitofrontal cortex and their disconnection from structures of the salience network.

The Role of the Primary Sensory Cortices in Early Language Processing.

The results of this magnetoencephalography study challenge two long-standing assumptions regarding the brain mechanisms of language processing: First, that linguistic processing proper follows sensory feature processing effected by bilateral activation of the primary sensory cortices that lasts about 100 msec from stimulus onset. Second, that subsequent linguistic processing is effected by left hemisphere networks outside the primary sensory areas, including Broca's and Wernicke's association cortices. Here we present evidence that linguistic analysis begins almost synchronously with sensory, prelinguistic verbal input analysis and that the primary cortices are also engaged in these linguistic analyses and become, consequently, part of the left hemisphere language network during language tasks. These findings call for extensive revision of our conception of linguistic processing in the brain.

Is it time to replace the Wada test and put awake craniotomy to sleep?

The question we address here is whether the invasive presurgical brain mapping approaches of direct cortical stimulation and of the Wada procedure can be replaced by noninvasive functional neuroimaging methods (functional magnetic resonance imaging [fMRI], magnetoencephalography [MEG], transcranial magnetic stimulation and [TMS]). First, we outline the reasons for contemplating such a replacement. Second, we present evidence to the effect that the efficacy of the invasive and noninvasive methods, while suboptimal, is comparable. Third, we discuss additional advantages of noninvasive presurgical brain mapping and conclude that there are no longer compelling reasons for opting for invasive mapping in many if not most cases provided that the non-invasive methods are available.

Non-Invasive Mapping of the Neuronal Networks of Language.

This review consists of three main sections. In the first, the Introduction, the main theories of the neuronal mediation of linguistic operations, derived mostly from studies of the effects of focal lesions on linguistic performance, are summarized. These models furnish the conceptual framework on which the design of subsequent functional neuroimaging investigations is based. In the second section, the methods of functional neuroimaging, especially those of functional Magnetic Resonance Imaging (fMRI) and of Magnetoencephalography (MEG), are detailed along with the specific activation tasks employed in presurgical functional mapping. The reliability of these non-invasive methods and their validity, judged against the results of the invasive methods, namely, the "Wada" procedure and Cortical Stimulation Mapping (CSM), is assessed and their use in presurgical mapping is justified. In the third and final section, the applications of fMRI and MEG in basic research are surveyed in the following six sub-sections, each dealing with the assessment of the neuronal networks for (1) the acoustic and phonological, (2) for semantic, (3) for syntactic, (4) for prosodic operations, (5) for sign language and (6) for the operations of reading and the mechanisms of dyslexia.

MEG language mapping using a novel automatic ECD algorithm in comparison with MNE, dSPM, and DICS beamformer.

Introduction: The single equivalent current dipole (sECD) is the standard clinical procedure for presurgical language mapping in epilepsy using magnetoencephalography (MEG). However, the sECD approach has not been widely used in clinical assessments, mainly because it requires subjective judgements in selecting several critical parameters. To address this limitation, we developed an automatic sECD algorithm (AsECDa) for language mapping. Methods: The localization accuracy of the AsECDa was evaluated using synthetic MEG data. Subsequently, the reliability and efficiency of AsECDa were compared to three other common source localization methods using MEG data recorded during two sessions of a receptive language task in 21 epilepsy patients. These methods include minimum norm estimation (MNE), dynamic statistical parametric mapping (dSPM), and dynamic imaging of coherent sources (DICS) beamformer. Results: For the synthetic single dipole MEG data with a typical signal-to-noise ratio, the average localization error of AsECDa was less than 2 mm for simulated superficial and deep dipoles. For the patient data, AsECDa showed better test-retest reliability (TRR) of the language laterality index (LI) than MNE, dSPM, and DICS beamformer. Specifically, the LI calculated with AsECDa revealed excellent TRR between the two MEG sessions across all patients (Cor = 0.80), while the LI for MNE, dSPM, DICS-event-related desynchronization (ERD) in the alpha band, and DICS-ERD in the low beta band ranged lower (Cor = 0.71, 0.64, 0.54, and 0.48, respectively). Furthermore, AsECDa identified 38% of patients with atypical language lateralization (i.e., right lateralization or bilateral), compared to 73%, 68%, 55%, and 50% identified by DICS-ERD in the low beta band, DICS-ERD in the alpha band, MNE, and dSPM, respectively. Compared to other methods, AsECDa's results were more consistent with previous studies that reported atypical language lateralization in 20-30% of epilepsy patients. Discussion: Our study suggests that AsECDa is a promising approach for presurgical language mapping, and its fully automated nature makes it easy to implement and reliable for clinical evaluations.

Single-trial magnetoencephalography signals encoded as an unfolding decision process.

The model of a stochastic decision process unfolding in motor and premotor regions of the brain was encoded in single-trial magnetoencephalographic (MEG) recordings while ten healthy subjects performed a sensorimotor Reaction Time (RT) task. The duration of single-trial MEG signals preceding the motor response, recorded over the motor cortex contralateral to the responding hand, co-varied with RT across trials according to the model's prediction. Furthermore, these signals displayed the same properties of a "rising-to-a-fixed-threshold" decision process as posited by the model and observed in the activity of single neurons in the primate cortex. The present findings demonstrate that non-averaged, single-trial MEG recordings can be used to test models of cognitive processes, like decision-making, in humans.

Diffusion tensor quantification and cognitive correlates of the macrostructure and microstructure of the corpus callosum in typically developing and dyslexic children.

Noninvasive quantitative MRI methods, such as diffusion tensor imaging (DTI), can offer insights into the structure-function relationships in human developmental brain disorders. In this article, we quantified the macrostructural and microstructural attributes of the corpus callosum (CC) in children with dyslexia and in typically developing readers of comparable age and gender. Diffusion anisotropy, and mean, radial and axial diffusivities of cross-sectional CC subregions were computed using a validated DTI methodology. The normalized posterior CC area was enlarged in children with dyslexia relative to that in typically developing children. Moreover, the callosal microstructural attributes, such as the mean diffusivity of the posterior middle sector of the CC, correlated significantly with measures of word reading and reading comprehension. Reading group differences in fractional anisotropy, mean diffusivity and radial diffusivity were observed in the posterior CC (CC5). This study demonstrates the utility of regional DTI measurements of the CC in understanding the neurobiology of reading disorders.

WITHDRAWN: fMRI correlates of visual working memory: What vs. where.

This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

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.

Temporo-parietal brain activity as a longitudinal predictor of response to educational interventions among middle school struggling readers.

Spatiotemporal brain activation profiles were obtained from 27 middle school students experiencing difficulties in reading comprehension as well as word-level skills (RD) and 23 age- and IQ-matched non-reading impaired students during performance of an oral pseudoword reading task using Magnetoencephalography (MEG). Based on their scores on standardized reading fluency tests 1 year later, students with RD who showed significant improvement were classified as Adequate Responders (AR) whereas those not demonstrating such gains were classified as Inadequate Responders (IR). At baseline, activation profiles of the AR group featured increased activity in the left supramarginal and angular gyri, as well as in the superior and middle temporal gyri, bilaterally compared to IR. The degree of activity in these regions was a significant predictor of the amount of subsequent gains in reading fluency. These results extend previous functional brain imaging findings of beginning readers, suggesting that recruitment of brain areas that typically serve as key components of the brain circuit for reading is an important factor in determining response to intervention in older struggling readers.

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.

Presurgical Functional Mapping with Magnetoencephalography.

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.

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.

The auditory and association cortex and language evaluation methods.

This chapter presents a summary of current notions regarding cortical specialization for language and a description of the methods employed for the assessment of that specialization. We distinguish between the "canonical" model of language specialization as it evolved from the early observations of Broca and Wernicke, implicating the inferior frontal gyrus and the posterior temporal cortex of the speech dominant hemisphere (usually the left) and its modern variants that are based on both detailed studies of lesion-symptom correlations and on the results of functional brain mapping methods. The latter fall into two categories. The first includes the invasive ones, namely the Wada procedure for assessing hemispheric dominance for speech and cortical stimulation mapping (whether intraoperative or extraoperative) for identifying cortical nodes or "hubs" of the neuronal network for language. The second category includes the noninvasive methods of functional magnetic resonance imaging, magnetoencephalography, and transcranial magnetic stimulation used for both assessment of hemispheric dominance for language and for localization of the cortical nodes of the language network. The advantages and the shortcomings of all methods are juxtaposed to facilitate selection of particular methods of assessment of the locus of the language network in particular cases.

Typical and Aberrant Functional Brain Flexibility: Lifespan Development and Aberrant Organization in Traumatic Brain Injury and Dyslexia.

Intrinsic functional connectivity networks derived from different neuroimaging methods and connectivity estimators have revealed robust developmental trends linked to behavioural and cognitive maturation. The present study employed a dynamic functional connectivity approach to determine dominant intrinsic coupling modes in resting-state neuromagnetic data from 178 healthy participants aged 8-60 years. Results revealed significant developmental trends in three types of dominant intra- and inter-hemispheric neuronal population interactions (amplitude envelope, phase coupling, and phase-amplitude synchronization) involving frontal, temporal, and parieto-occipital regions. Multi-class support vector machines achieved 89% correct classification of participants according to their chronological age using dynamic functional connectivity indices. Moreover, systematic temporal variability in functional connectivity profiles, which was used to empirically derive a composite flexibility index, displayed an inverse U-shaped curve among healthy participants. Lower flexibility values were found among age-matched children with reading disability and adults who had suffered mild traumatic brain injury. The importance of these results for normal and abnormal brain development are discussed in light of the recently proposed role of cross-frequency interactions in the fine-grained coordination of neuronal population activity.

Aberrant Whole-Brain Transitions and Dynamics of Spontaneous Network Microstates in Mild Traumatic Brain Injury.

Dynamic Functional Connectivity (DFC) analysis is a promising approach for the characterization of brain electrophysiological activity. In this study, we investigated abnormal alterations due to mild Traumatic Brain Injury (mTBI) using DFC of the source reconstructed magnetoencephalographic (MEG) resting-state recordings. Brain activity in several well-known frequency bands was first reconstructed using beamforming of the MEG data to determine ninety anatomical brain regions of interest. A DFC graph was formulated using the imaginary part of phase-locking values, which were obtained from 30 mTBI patients and 50 healthy controls (HC). Subsequently, we estimated normalized Laplacian transformations of individual, statistically and topologically filtered quasi-static graphs. The corresponding eigenvalues of each node synchronization were then computed and through the neural-gas algorithm, we quantized the evolution of the eigenvalues resulting in distinct network microstates (NMstates). The discrimination level between the two groups was assessed using an iterative cross-validation classification scheme with features either the NMstates in each frequency band, or the combination of the so-called chronnectomics (flexibility index, occupancy time of NMstate, and Dwell time) with the complexity index over the evolution of the NMstates across all frequency bands. Classification performance based on chronnectomics showed 80% accuracy, 99% sensitivity, and 49% specificity. However, performance was much higher (accuracy: 91-97%, sensitivity: 100%, and specificity: 77-93%) when focusing on the microstates. Exploring the mean node degree within and between brain anatomical networks (default mode network, frontoparietal, occipital, cingulo-opercular, and sensorimotor), a reduced pattern occurred from lower to higher frequency bands, with statistically significant stronger degrees for the HC than the mTBI group. A higher entropic profile on the temporal evolution of the modularity index was observed for both NMstates for the mTBI group across frequencies. A significant difference in the flexibility index was observed between the two groups for the ß frequency band. The latter finding may support a central role of the thalamus impairment in mTBI. The current study considers a complete set of frequency-dependent connectomic markers of mTBI-caused alterations in brain connectivity that potentially could serve as markers to assess the return of an injured subject back to normality.

The power of sample size through a multi-scanner approach in MR neuroimaging regression analysis: evidence from Alzheimer's disease with and without depression.

The inconsistency of volumetric results often seen in MR neuroimaging studies can be partially attributed to small sample sizes and variable data analysis approaches. Increased sample size through multi-scanner studies can tackle the former, but combining data across different scanner platforms and field-strengths may introduce a variability factor capable of masking subtle statistical differences. To investigate the sample size effect on regression analysis between depressive symptoms and grey matter volume (GMV) loss in Alzheimer's disease (AD), a retrospective multi-scanner investigation was conducted. A cohort of 172 AD patients, with or without comorbid depressive symptoms, was studied. Patients were scanned with different imaging protocols in four different MRI scanners operating at either 1.5 T or 3.0 T. Acquired data were uniformly analyzed using the computational anatomy toolbox (CAT12) of the statistical parametric mapping (SPM12) software. Single- and multi-scanner regression analyses were applied to identify the anatomical pattern of correlation between GM loss and depression severity. A common anatomical pattern of correlation between GMV loss and increased depression severity, mostly involving sensorimotor areas, was identified in all patient subgroups imaged in different scanners. Analysis of the pooled multi-scanner data confirmed the above finding employing a more conservative statistical criterion. In the retrospective multi-scanner setting, a significant correlation was also exhibited for temporal and frontal areas. Increasing the sample size by retrospectively pooling multi-scanner data, irrespective of the acquisition platform and parameters employed, can facilitate the identification of anatomical areas with a strong correlation between GMV changes and depression symptoms in AD patients.

MEG correlates of bimodal encoding of faces and persons' names.

Learning associations between people's faces and names is a universal cognitive function with important social implications. The goal of the present study was to examine brain activity patterns associated with cross-modal encoding of names and faces. Learning face-name pairs was compared to unimodal learning tasks using the same visual and auditory stimuli. Spatiotemporal brain activation profiles were obtained with magnetoencephalography using an automated source estimation method. Results showed activation foci in left (for names) and right (for faces) temporal lobe perisylvian cortices, predominantly right-hemisphere occipital and occipitotemporal regions (for faces), and right hemisphere dorsolateral prefrontal regions during the encoding phase for both types of stimuli presented in isolation. Paired (face-name) stimulus presentation elicited bilateral prefrontal and temporal lobe perisylvian activity for faces and enhanced visual cortex activation in response to names (compared to names in the unpaired condition). These findings indicate distinct patterns of brain activation during the formation of associations between meaningful visual and auditory stimuli.

Aberrant spatiotemporal activation profiles associated with math difficulties in children: a magnetic source imaging study.

The study investigates the relative degree and timing of cortical activation in parietal, temporal, and frontal regions during simple arithmetic tasks in children who experience math difficulties. Real-time brain activity was measured with magnetoencephalography during simple addition and numerosity judgments in students with math difficulties and average or above average reading skills (MD group, N = 14), students with below average scores on both math and basic reading tests (MD/RD group, N = 16) and students with above average scores on standardized math tests (control group, N = 25). Children with MD showed increased degree of neurophysiological activity in inferior and superior parietal regions in the right hemisphere compared to both controls and MD/RD students. Left hemisphere inferior parietal regions did not show the expected task-related changes and showed activity at a significant temporal delay. MD students also showed increased early engagement of prefrontal cortices. Taken together, these findings may indicate increased reliance on a network of right hemisphere parietal (and possibly frontal areas as well) for simple math calculations in students who experience math difficulties but perform within normal range in reading.