A multimodal imaging approach to foreign accent syndrome. A case report.

This article describes a case of Foreign accent syndrome (FAS) in an Italian woman who developed a Canadian-like foreign accent without brain damage (functional FAS). The patient underwent an in-depth neuroimaging and (neuro)psychological evaluation. Language networks in the frontotemporal-parietal areas were typically activated bilaterally through fMRI and MEG assessments based on task-based data. Resting-state fMRI showed preserved connectivity between language areas. An obsessive-compulsive personality profile and mild anxiety were found, suggesting psychological and psychiatric factors may be relevant. Accordingly with our findings, multimodal imaging is beneficial to understand FAS neurological and functional etiologies.

Visual behaviors in disorders of consciousness: Disentangling conscious visual processing by a multimodal approach.

One of the major challenges for clinicians who treat patients with Disorders of Consciousness (DoCs) concerns the detection of signs of consciousness that distinguish patients in Vegetative State from those in Minimally Conscious State. Recent studies showed how visual responses to tailored stimuli are one of the first evidence revealing that one patient is changing from one state to another. This study aimed to explore the integrity of the neural structures being part of the visual system in patients with DoCs manifesting a reflexive behavior (visual blink) and in those manifesting a cognitively and cortically mediated behavior (visual pursuit). We collected instrumental data using specialized equipment (EEG following the rules of the International 10-20 system, 3T Magnetic Resonance, and Positron Emission Tomography) in 54 DoC patients. Our results indicated that visual pursuit group showed a better fVEPs response than the visual blink group, because of a greater area under the N2/P2 component of fVEPs (AUC could be seen as an indicator of the residual activity of visual areas). Considering neuroimaging data, the main structural differences between groups were found in the retrochiasmatic areas, specifically in the right optic radiation and visual cortex (V1), areas statistically less impaired in patients able to perform a visual pursuit. FDG-PET analysis confirmed difference between groups at the level of the right calcarine cortex and neighboring right lingual gyrus. In conclusion, although there are methodological and theoretical limitations that should be considered, our study suggests a new perspective to consider for a future diagnostic protocol.

Towards the Automatic Localization of the Irritative Zone Through Magnetic Source Imaging.

The present work aims at validating a Bayesian multi-dipole modeling algorithm (SESAME) in the clinical scenario consisting of localizing the generators of single interictal epileptiform discharges from resting state magnetoencephalographic recordings. We use the results of Equivalent Current Dipole fitting, performed by an expert user, as a benchmark, and compare the results of SESAME with those of two widely used source localization methods, RAP-MUSIC and wMNE. In addition, we investigate the relation between post-surgical outcome and concordance of the surgical plan with the cerebral lobes singled out by the methods. Unlike dipole fitting, the tested algorithms do not rely on any subjective channel selection and thus contribute towards making source localization more unbiased and automatic. We show that the two dipolar methods, SESAME and RAP-MUSIC, generally agree with dipole fitting in terms of identified cerebral lobes and that the results of the former are closer to the fitted equivalent current dipoles than those of the latter. In addition, for all the tested methods and particularly for SESAME, concordance with surgical plan is a good predictor of seizure freedom while discordance is not a good predictor of poor post-surgical outcome. The results suggest that the dipolar methods, especially SESAME, represent a reliable and more objective alternative to manual dipole fitting for clinical applications in the field of epilepsy surgery.

Early clinical and EEG findings associated with the outcome in childhood absence epilepsy.

OBJECTIVES: The objective of this study was to investigate several clinical electroencephalogram (EEG) findings possibly predicting the early response to antiepileptic drugs (AEDs) and the late outcome in children with clinical EEG features fitting the syndromic diagnosis of childhood absence epilepsy (CAE). METHODS: In 117 untreated patients with typical absences, we analyzed clinical EEG features, and resting EEG activity using partial directed coherence to calculate out- and inflow of cortical oscillations in different regions of interest. RESULTS: Absences began before 4 years in 12.0%, at 4-9.5 years in 71.8%, and at 10-13 years in 16.2% of the cases. Valproate was started in 91 patients and ethosuximide in 27. With one of AEDs, 77.8% reached seizure control, while the remaining patients needed to switch to the alternative AED. Only 5.9% patients remained drug-resistant. Absences with simple automatisms were the only feature associated with a lack of response to the first AED. Connectivity analysis of resting EEGs showed increased frontal outflow in patients compared with controls, which was significantly greater in the nonresponders to the first AED than in responders. Among the 91 patients followed for 61.2 ±â€¯31.7 months, 14.2% relapsed after a seizure-free period, without differences between the responders to the first or second AED. CONCLUSIONS: The assessment of electroclinical features provided only minimal prognostic indices. The enhanced outflow of frontal oscillations suggests a circuitry dysfunction significantly greater in the nonresponder to the early treatment. Seizure relapses were rare and comparable in patients who reached seizure freedom with first or second AED, indicating that the resistance to one AED does not influence the outcome.

A comparative study on assessment procedures and metric properties of two scoring systems of the Coma Recovery Scale-Revised items: standard and modified scores.

OBJECTIVE: The study compared the metric characteristics (discriminant capacity and factorial structure) of two different methods for scoring the items of the Coma Recovery Scale-Revised and it analysed scale scores collected using the standard assessment procedure and a new proposed method. DESIGN: Cross sectional design/methodological study. SETTING: Inpatient, neurological unit. PARTICIPANTS: A total of 153 patients with disorders of consciousness were consecutively enrolled between 2011 and 2013. INTERVENTION: All patients were assessed with the Coma Recovery Scale-Revised using standard (rater 1) and inverted (rater 2) procedures. MAIN OUTCOME MEASURES: Coma Recovery Scale-Revised score, number of cognitive and reflex behaviours and diagnosis. RESULTS: Regarding patient assessment, rater 1 using standard and rater 2 using inverted procedures obtained the same best scores for each subscale of the Coma Recovery Scale-Revised for all patients, so no clinical (and statistical) difference was found between the two procedures. In 11 patients (7.7%), rater 2 noted that some Coma Recovery Scale-Revised codified behavioural responses were not found during assessment, although higher response categories were present. A total of 51 (36%) patients presented the same Coma Recovery Scale-Revised scores of 7 or 8 using a standard score, whereas no overlap was found using the modified score. Unidimensionality was confirmed for both score systems. CONCLUSION: The Coma Recovery Scale Modified Score showed a higher discriminant capacity than the standard score and a monofactorial structure was also supported. The inverted assessment procedure could be a useful evaluation method for the assessment of patients with disorder of consciousness diagnosis.

The Semantics of Natural Objects and Tools in the Brain: A Combined Behavioral and MEG Study.

Current literature supports the notion that the recognition of objects, when visually presented, is sub-served by neural structures different from those responsible for the semantic processing of their nouns. However, embodiment foresees that processing observed objects and their verbal labels should share similar neural mechanisms. In a combined behavioral and MEG study, we compared the modulation of motor responses and cortical rhythms during the processing of graspable natural objects and tools, either verbally or pictorially presented. Our findings demonstrate that conveying meaning to an observed object or processing its noun similarly modulates both motor responses and cortical rhythms; being natural graspable objects and tools differently represented in the brain, they affect in a different manner both behavioral and MEG findings, independent of presentation modality. These results provide experimental evidence that neural substrates responsible for conveying meaning to objects overlap with those where the object is represented, thus supporting an embodied view of semantic processing.

Grasping the semantic of actions: a combined behavioral and MEG study.

There is experimental evidence that the brain systems involved in action execution also play a role in action observation and understanding. Recently, it has been suggested that the sensorimotor system is also involved in language processing. Supporting results are slower response times and weaker motor-related MEG Beta band power suppression in semantic decision tasks on single action verbs labels when the stimulus and the motor response involve the same effector. Attenuated power suppression indicates decreased cortical excitability and consequent decreased readiness to act. The embodied approach forwards that the simultaneous involvement of the sensorimotor system in the processing of the linguistic content and in the planning of the response determines this language-motor interference effect. Here, in a combined behavioral and MEG study we investigated to what extent the processing of actions visually presented (i.e., pictures of actions) and verbally described (i.e., verbs in written words) share common neural mechanisms. The findings demonstrated that, whether an action is experienced visually or verbally, its processing engages the sensorimotor system in a comparable way. These results provide further support to the embodied view of semantic processing, suggesting that this process is independent from the modality of presentation of the stimulus, including language.

Corrigendum: Preservation of Language Processing and Auditory Performance in Patients With Disorders of Consciousness: A Multimodal Assessment.

[This corrects the article DOI: 10.3389/fneur.2020.526465.].

Analyzing the Loss and the Recovery of Consciousness: Functional Connectivity Patterns and Changes in Heart Rate Variability During Propofol-Induced Anesthesia.

The analysis of the central and the autonomic nervous systems (CNS, ANS) activities during general anesthesia (GA) provides fundamental information for the study of neural processes that support alterations of the consciousness level. In the present pilot study, we analyzed EEG signals and the heart rate (HR) variability (HRV) in a sample of 11 patients undergoing spinal surgery to investigate their CNS and ANS activities during GA obtained with propofol administration. Data were analyzed during different stages of GA: baseline, the first period of anesthetic induction, the period before the loss of consciousness, the first period after propofol discontinuation, and the period before the recovery of consciousness (ROC). In EEG spectral analysis, we found a decrease in posterior alpha and beta power in all cortical areas observed, except the occipital ones, and an increase in delta power, mainly during the induction phase. In EEG connectivity analysis, we found a significant increase of local efficiency index in alpha and delta bands between baseline and loss of consciousness as well as between baseline and ROC in delta band only and a significant reduction of the characteristic path length in alpha band between the baseline and ROC. Moreover, connectivity results showed that in the alpha band there was mainly a progressive increase in the number and in the strength of incoming connections in the frontal region, while in the beta band the parietal region showed mainly a significant increase in the number and in the strength of outcoming connections values. The HRV analysis showed that the induction of anesthesia with propofol was associated with a progressive decrease in complexity and a consequent increase in the regularity indexes and that the anesthetic procedure determined bradycardia which was accompanied by an increase in cardiac sympathetic modulation and a decrease in cardiac parasympathetic modulation during the induction. Overall, the results of this pilot study showed as propofol-induced anesthesia caused modifications on EEG signal, leading to a "rebalance" between long and short-range cortical connections, and had a direct effect on the cardiac system. Our data suggest interesting perspectives for the interactions between the central and autonomic nervous systems for the modulation of the consciousness level.

Visual fixation in disorders of consciousness: Development of predictive models to support differential diagnosis.

The visual fixation represents a doubtful behavioral sign to discriminate Vegetative from Minimally Conscious State (MCS). To disentangle its meaning, we fitted univariate and multivariable logistic regression models matching different neurophysiological and neuroimaging data of 54 patients with Disorders of Consciousness to select the best model predicting which visual performance (visual blink or pursuit) was shown by patients and the best predictors set. The best models found highlighted the importance of the structural MRI and the visual evoked potentials data in predicting visual pursuit. Then, a qualitative pilot test was made on four patients showing visual fixation revealing that the obtained models correctly predict whether the patients' visual performance could support/correlate to a cognitively mediated behavior. The present pilot models could help clinicians to evaluate if the visual fixation response can support the MCS diagnosis.

Distortion of the cortical motor map in patients with Unverricht-Lundborg disease: A combined TMS-MRI study.

OBJECTIVE: To assess functional organization of the motor cortex in patients with Unverricht-Lundborg disease (EPM1A) using a combined neurophysiologic and imaging approach. METHODS: EPM1A patients underwent transcranial magnetic stimulation (TMS)-based cortical mapping of the motor hand area. Moreover, they performed neuroimaging studies to assess functional magnetic resonance imaging (fMRI) activation maps related to motor hand task and cortical thickness (CTH) on T1-weighted 3D images. RESULTS: The hand cortical representation was different in EPM1A patients from that of the control subjects both in TMS and in fMRI brain mapping, characterized by a posterior dislocation and a mild reduction in the activation of motor areas. CTH analysis revealed a thinning of both precentral and paracentral areas in the patients. CONCLUSIONS: We hypothesize that the altered cortical motor map reflects a functional reorganization of the residual cortical neuronal pool of the sensorimotor hand areas driven by plastic reorganization and/or pathophysiological mechanisms. SIGNIFICANCE: Both pathophysiological process and plastic changes may represent two sides of the same phenomenon in the EPM1A patients; structural and functional brain mapping may help to identify functional reorganization of the cortical motor system.

Identifying the epileptogenic zone by four non-invasive imaging techniques versus stereo-EEG in MRI-negative pre-surgery epilepsy patients.

OBJECTIVE: We evaluated four imaging techniques, i.e. Electroencephalography (EEG)-functional Magnetic Resonance Imaging (MRI) (EEG-fMRI), High-resolution EEG (HR-EEG), Magnetoencephalography (MEG) and 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET), for the identification of the epileptogenic zone (EZ) in 41 patients with negative MRI, candidate to neurosurgery. METHODS: For each technique, results were compared to the Stereo-EEG. Diagnostic measures were calculated with respect to the post-surgical outcome, either for all the patients (39/41, two patients excluded) and for the subgroup of patients with the EZ involving more than one lobe (20/41). RESULTS: When considered individually, each functional technique showed accuracy values ranging 54,6%-63,2%, having PET, MEG and HR-EEG higher sensitivity, and EEG-fMRI higher specificity. In patients with multilobar epileptogenic zone, functional techniques achieved the best accuracies (up to 80%) when three techniques, including EEG-fMRI, were considered together. CONCLUSIONS: The study highlights the accuracy of a combination of functional imaging techniques in the identification of EZ in MRI negative focal epilepsy. The best diagnostic yield was obtained if the combination of PET, MEG (or HR-EEG as alternative), EEG-fMRI were considered together. SIGNIFICANCE: The functional imaging techniques may improve the presurgical workup of MRI negative focal epilepsy, if epileptogenic zone involves more than one lobe.

Preservation of Language Processing and Auditory Performance in Patients With Disorders of Consciousness: A Multimodal Assessment.

The impact of language impairment on the clinical assessment of patients suffering from disorders of consciousness (DOC) is unknown or underestimated and may mask the presence of conscious behavior. In a group of DOC patients (n = 11; time post-injury range: 5-252 months), we investigated the main neural functional and structural underpinnings of linguistic processing, and their relationship with the behavioral measures of the auditory function using the Coma Recovery Scale-Revised (CRS-R). We assessed the integrity of the brainstem auditory pathways, of the left superior temporal gyrus and arcuate fasciculus, the neural activity elicited by passive listening of an auditory language task, and the mean hemispheric glucose metabolism. Our results support the hypothesis of a relationship between the level of preservation of the investigated structures/functions and the CRS-R auditory subscale scores. Moreover, our findings indicate that patients in minimally conscious state minus (MCS-): (1) when presenting the auditory startle (at the CRS-R auditory subscale) might be aphasic in the receptive domain, being severely impaired in the core language structures/functions; (2) when presenting the localization to sound might retain language processing, being almost intact or intact in the core language structures/functions. Despite the small group of investigated patients, our findings provide a grounding of the clinical measures of the CRS-R auditory subscale in the integrity of the underlying auditory structures/functions. Future studies are needed to confirm our results that might have important consequences for the clinical practice.

Bayesian multi-dipole modelling in the frequency domain.

BACKGROUND: Magneto- and Electro-encephalography record the electromagnetic field generated by neural currents with high temporal frequency and good spatial resolution, and are therefore well suited for source localization in the time and in the frequency domain. In particular, localization of the generators of neural oscillations is very important in the study of cognitive processes in the healthy and in the pathological brain. NEW METHOD: We introduce the use of a Bayesian multi-dipole localization method in the frequency domain. Given the Fourier Transform of the data at one or multiple frequencies and/or trials, the algorithm approximates numerically the posterior distribution with Monte Carlo techniques. RESULTS: We use synthetic data to show that the proposed method behaves well under a wide range of experimental conditions, including low signal-to-noise ratios and correlated sources. We use dipole clusters to mimic the effect of extended sources. In addition, we test the algorithm on real MEG data to confirm its feasibility. COMPARISON WITH EXISTING METHOD(S): Throughout the whole study, DICS (Dynamic Imaging of Coherent Sources) is used systematically as a benchmark. The two methods provide similar general pictures; the posterior distributions of the Bayesian approach contain much richer information at the price of a higher computational cost. CONCLUSIONS: The Bayesian method described in this paper represents a reliable approach for localization of multiple dipoles in the frequency domain.

Epileptic spikes in Rasmussen's encephalitis: Migratory pattern and short-term evolution. A MEG study.

OBJECTIVE: We aimed this study at identifying cortical areas involved in the generation of interictal spikes in Rasmussen's Encephalitis (RE) patients using magnetoencephalography (MEG), at comparing spike localization with the degree of cortical atrophy detected by MRI, and at identifying short-term changes during the follow-up. METHODS: Five patients with RE underwent two MEG and magnetic resonance imaging (MRI) (six months interval). The sources of visually detected spikes were estimated using equivalent current dipoles technique; these were then superimposed on individual MRI and clustered; the locations of the clusters were related to the MRI stage of cortical atrophy. RESULTS: All patients showed spikes and clusters located in different cortical areas in both recordings; the locations had a limited correspondence with cortical atrophy. The second recordings showed changes in the localisation of spikes and clusters, and confirmed the dissimilarities with neuroradiological abnormalities. CONCLUSIONS: The presence of clusters of spikes of variable localisation suggests that RE progresses in a multifocal and fluctuating manner. The cortical areas most involved in epileptogenesis did not completely coincide with the most atrophic areas. SIGNIFICANCE: MEG can contribute to evaluating multifocal hemispheric spikes in RE and to better understand the time course of epileptogenic process.

Integration of Functional Magnetic Resonance Imaging and Magnetoencephalography Functional Maps Into a CyberKnife Planning System: Feasibility Study for Motor Activity Localization and Dose Planning.

OBJECTIVE: Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) provide noninvasive localization of eloquent brain areas for presurgical planning. The aim of this study is the integration of MEG and fMRI maps into a CyberKnife (CK) system to optimize dose planning. METHODS: Four patients with brain metastases in the motor area underwent functional imaging study of the hand motor cortex before radiosurgery. MEG data were acquired during a visually cued hand motor task. Motor activations were identified also using an fMRI block-designed paradigm. MEG and fMRI maps were then integrated into a CK system and contoured as organs at risk for treatment planning optimization. RESULTS: The integration of fMRI data into the CK system was achieved for all patients by means of a standardized protocol. We also implemented an ad hoc pipeline to convert the MEG signal into a DICOM standard, to make sure that it was readable by our CK treatment planning system. Inclusion of the activation areas into the optimization plan allowed the creation of treatment plans that reduced the irradiation of the motor cortex yet not affecting the brain peripheral dose. CONCLUSIONS: The availability of advanced neuroimaging techniques is playing an increasingly important role in radiosurgical planning strategy. We successfully imported MEG and fMRI activations into a CK system. This additional information can improve dose sparing of eloquent areas, allowing a more comprehensive investigation of the related dose-volume constraints that in theory could translate into a gain in tumor local control, and a reduction of neurological complications.

Altered resting state effective connectivity in long-standing vegetative state patients: an EEG study.

OBJECTIVE: Recent evidence mainly based on hemodynamic measures suggests that the impairment of functional connections between different brain areas may help to clarify the neuronal dysfunction occurring in patients with disorders of consciousness (DOC). The aim of this study was to evaluate effective EEG connectivity in a cohort of 18 patients in a chronic vegetative state (VS) observed years after the occurrence of hypoxic (eight) and traumatic or hemorrhagic brain insult. METHODS: we analysed the EEG signals recorded under resting conditions using a frequency domain linear index of connectivity (partial directed coherence: PDC) estimated from a multivariate autoregressive model. The results were compared with those obtained in ten healthy controls. RESULTS: Our findings indicated significant connectivity changes in EEG activities in delta and alpha bands. The VS patients showed a significant and widespread decrease in delta band connectivity, whereas the alpha activity was hyper-connected in the central and posterior cortical regions. CONCLUSION: These changes suggest the occurrence of severe circuitry derangements probably due to the loose control of the subcortical connections. The alpha hyper-synchronisation may be due to simplified networks mainly involving the short-range connections between intrinsically oscillatory cortical neurons that generate aberrant EEG alpha sources. This increased connectivity may be interpreted as a reduction in information capacity, implying an increasing prevalence of stereotypic activity patterns. SIGNIFICANCE: Our observations suggest a remarkable rearrangement of connectivity in patients with long-standing VS. We hypothesize that in persistent VS, after a first period characterized by a breakdown of cortical connectivity, neurodegenerative processes, largely independent from the type of initial insult, lead to cortex de-afferentation and to a severe reduction of possible cortical activity patterns and states.

Assessment of patients with disorder of consciousness: do different Coma Recovery Scale scoring correlate with different settings?

Differential diagnosis between Vegetative State and Minimally Conscious State is a challenging task that requires specific assessment scales, involvement of expert neuropsychologists or physicians and use of tailored stimuli for eliciting behavioural responses. Although misdiagnosis rate as high as 40% has been reported, no clear guidelines are available in literature on the optimal setting for assessment. The present study aims to analyse score differences in behavioural assessments of persons with disorders of consciousness (DOC) with or without family members and to determine whether the presence of caregivers could improve clinical accuracy in diagnostic evaluation. The research was conducted on 92 adults with DOC among 153 consecutive patients enrolled in the Coma Research Centre of the Neurological Institute C. Besta of Milan between January 2011 and May 2013. The results indicate that in almost half of the sample the scoring, thus the performance, observed with caregivers was better than without them. Furthermore, in 16% of the sample, when assessment was performed with caregivers there was a change in diagnosis, from Vegetative to Minimally Conscious State or from that to Severe Disability. Finally, statistical differences were found in relation to diagnosis between mean scores in the "visual function" Coma Recovery Scale revised's subscale obtained by raters plus caregiver and rates only assessment. This study demonstrates how the presence of caregivers can positively affect behavioural assessments of persons with DOC, thus contributing to the definition of the optimal setting for behavioural evaluation of patients, to decrease misdiagnosis rates.