Disruptions in modular structure and network integration of language-related network predict language performance in temporal lobe epilepsy: Evidence from graph-based analysis.

OBJECTIVE: Temporal lobe epilepsy (TLE) is a network disorder that alters the total organization of the language-related network. Task-based functional magnetic resonance imaging (fMRI) aimed at functional connectivity is a direct method to investigate how the network is reorganized. However, such studies are scarce and represented mostly by the resting-state analysis of the individual connections between regions. To fill this gap, we used a graph-based analysis, which allows us to cover the total language-related network changes, such as disruptions in an integration/segregation balance, during a language task in TLE. METHODS: We collected task-based fMRI data with sentence completion from 19 healthy controls and 28 people with left TLE. Using graph-based analysis, we estimated how the language-related network segregated into modules and tested whether they differed between groups. We evaluated the total network integration and the integration within modules. To assess intermodular integration, we considered the number and location of connector hubs-regions with high connectivity. RESULTS: The language-related network was differently segregated during language processing in the groups. While healthy controls showed a module consisting of left perisylvian regions, people with TLE exhibited a bilateral module formed by the anterior language-related areas and a module in the left temporal lobe, reflecting hyperconnectivity within the epileptic focus. As a consequence of this reorganization, there was a statistical tendency that the dominance of the intramodular integration over the total network integration was greater in TLE, which predicted language performance. The increase in the number of connector hubs in the right hemisphere, in turn, was compensatory in TLE. SIGNIFICANCE: Our study provides insights into the reorganization of the language-related network in TLE, revealing specific network changes in segregation and integration. It confirms reduced global connectivity and compensation across the healthy hemisphere, commonly observed in epilepsy. These findings advance the understanding of the network-based reorganizational processes underlying language processing in TLE.

The emotional component of inner speech: A pilot exploratory fMRI study.

Inner speech is one of the most important human cognitive processes. Nevertheless, until now, many aspects of inner speech, particularly the emotional characteristics of inner speech, remain poorly understood. The main objectives of our study are to identify the neural substrate for the emotional (prosodic) dimension of inner speech and brain structures that control the suppression of expression in inner speech. To achieve these goals, a pilot exploratory fMRI study was carried out on 33 people. The subjects listened to pre-recorded phrases or individual words pronounced with different emotional connotations, after which they were internally spoken with the same emotion or with suppression of expression (neutral). The results show that there is an emotional component in inner speech, which is encoded by similar structures as in spoken speech. The unique role of the caudate nuclei in the suppression of expression in the inner speech was also shown.

A New Functional Magnetic Resonance Imaging Localizer for Preoperative Language Mapping Using a Sentence Completion Task: Validity, Choice of Baseline Condition, and Test-Retest Reliability.

To avoid post-neurosurgical language deficits, intraoperative mapping of the language function in the brain can be complemented with preoperative mapping with functional magnetic resonance imaging (fMRI). The validity of an fMRI "language localizer" paradigm crucially depends on the choice of an optimal language task and baseline condition. This study presents a new fMRI "language localizer" in Russian using overt sentence completion, a task that comprehensively engages the language function by involving both production and comprehension at the word and sentence level. The paradigm was validated in 18 neurologically healthy volunteers who participated in two scanning sessions, for estimating test-retest reliability. For the first time, two baseline conditions for the sentence completion task were compared. At the group level, the paradigm significantly activated both anterior and posterior language-related regions. Individual-level analysis showed that activation was elicited most consistently in the inferior frontal regions, followed by posterior temporal regions and the angular gyrus. Test-retest reliability of activation location, as measured by Dice coefficients, was moderate and thus comparable to previous studies. Test-retest reliability was higher in the frontal than temporo-parietal region and with the most liberal statistical thresholding compared to two more conservative thresholding methods. Lateralization indices were expectedly left-hemispheric, with greater lateralization in the frontal than temporo-parietal region, and showed moderate test-retest reliability. Finally, the pseudoword baseline elicited more extensive and more reliable activation, although the syllable baseline appears more feasible for future clinical use. Overall, the study demonstrated the validity and reliability of the sentence completion task for mapping the language function in the brain. The paradigm needs further validation in a clinical sample of neurosurgical patients. Additionally, the study contributes to general evidence on test-retest reliability of fMRI.

'Moderate global aphasia': A generalized decline of language processing caused by glioma surgery but not stroke.

Unlike stroke, neurosurgical removal of left-hemisphere gliomas acts upon a reorganized language network and involves brain areas rarely damaged by stroke. We addressed whether this causes the profiles of neurosurgery- and stroke-induced language impairments to be distinct. K-means clustering of language assessment data (neurosurgery cohort: N = 88, stroke cohort: N = 95) identified similar profiles in both cohorts. But critically, a cluster of individuals with specific phonological deficits was only evident in the stroke but not in the neurosurgery cohort. Thus, phonological deficits are less clearly distinguished from other language deficits after glioma surgery compared to stroke. Furthermore, the correlations between language production and comprehension scores at different linguistic levels were more extensive in the neurosurgery than in the stroke cohort. Our findings suggest that neurosurgery-induced language impairments do not correspond to those caused by stroke, but rather manifest as a 'moderate global aphasia' - a generalized decline of language processing abilities.

Phase 3 trial of coronavir (favipiravir) in patients with mild to moderate COVID-19.

Favipiravir has demonstrated efficacy against the SARS-CoV-2 virus in several preliminary studies. This study aimed to evaluate the efficacy and safety of favipiravir for treatment of mild to moderate COVID-19 in outpatients and hospitalized patients. We conducted an open-label, randomized, active-controlled trial of a generic form of favipiravir in patients with COVID-19 confirmed by PCR-test. Eligible patients (18-60 years) after stratification were randomly assigned (in a 2:1 ratio) to receive either favipiravir (1800 mg BID on day 1, followed by 800 mg BID for up to 9 days), or standard of care (SOC) treatment (umifenovir + intranasal interferon alpha-2b, or hydroxychloroquine) for up to 10 days. The co-primary outcomes were the time to clinical improvement and the time to viral clearance. Among 190 patients assessed for eligibility 168 were randomized to favipiravir (n=112) or to SOC (n=56) group. The median time to clinical improvement was 6.0 days (IQR 4.0; 9.3) in the favipiravir group and 10.0 (IQR 5.0; 21.0) days in the SOC group; the median difference was 4 days (HR 1.63; 95% CI 1.14-2.34; P=0.007). The statistically significant difference in the median time to viral clearance was observed only for hospitalized patients: 3.0 (IQR 3.0; 3.0) days in the favipiravir group vs. 5.0 (IQR 4.5; 5.5) days in the SOC group (HR 2.11; 95% CI 1.04-4.31; P=0.038). The rate of viral elimination on Day 5 in the favipiravir group was significantly higher than in SOC group: 81.2% vs. 67.9% (RR 1.22; 05% CI 1.00-1.48; P=0.022). The rate of clinical improvement on Day 7 in the favipiravir group was 1.5-fold higher than in SOC group: 52.7% vs. 35.8% (RR 1.50; 95% CI 1.02-2.22; P=0.020). Favipiravir was well-tolerated and the most common adverse reactions were asymptomatic hyperuricemia, transient elevation of ALT & AST, and mild gastrointestinal disorders. Favipiravir was superior to the SOC in shortening the time to clinical improvement in patients with mild to moderate COVID-19.

Functional linguistic specificity of the left frontal aslant tract for spontaneous speech fluency: Evidence from intraoperative language mapping.

The left frontal aslant tract (FAT) has been proposed to be relevant for language, and specifically for spontaneous speech fluency. However, there is missing causal evidence that stimulation of the FAT affects spontaneous speech, and not language production in general. We present a series of 12 neurosurgical cases with awake language mapping of the cortex near the left FAT. Tasks for language mapping included the commonly used action picture naming, and sentence completion, tapping more specifically into spontaneous speech. A task dissociation was found in 10 participants: while being stimulated on specific sites, they were able to name a picture but could not complete a sentence. Overlaying of these sites on preoperative white-matter tract reconstructions revealed that in each individual case they were located on cortical terminations of the FAT. This corroborates the language functional specificity of the left FAT as a tract underlying fluent spontaneous speech.

Calcification of the epiglottis presenting as foreign body sensation in the neck.

The epiglottis plays an important role in preventing food of different consistencies from entering the airway during swallowing. Calcification of epiglottis can, potentially, alter and limit its movement causing aspiration amongst other swallowing problems. Isolated calcification of the epiglottis and its clinical presentation remains a poorly understood entity for radiologists as well as clinicians. Therefore, it is important to recognize the imaging features of epiglottic calcification, and it's known clinical presentations to help clinicians with early diagnosis and management.

Age and sex variability and normal reference values for the V(MCA)/V(ICA) index.

BACKGROUND AND PURPOSE: The index of mean blood flow velocity (V) in the middle cerebral artery (MCA) divided by respective velocity in the ipsilateral internal carotid artery (ICA), or V(MCA)/V(ICA) index, is commonly used as a marker of vasospasm, although reference values are not established. We sought to provide reference data for these velocities and index. METHODS: Transcranial color-coded duplex and carotid duplex sonography was performed in 335 healthy volunteers (211 women, 124 men; mean age +/- SD, 42 +/- 18 years; range, 18-86 years). Age analyses were based on three groups: I, <40; II, 40-60; and III, >60 years. The V(MCA)/V(ICA) index was calculated based on angle-corrected blood flow velocities determined in the MCA and extracranial ICA. RESULTS: Mean flow velocities in the MCA and ICA diminished with increasing age, most pronounced in those subjects >40 years. The V(MCA)/V(ICA) index increased significantly (1.67 + 0.005 [age]; P < .05) with age in women, but not in men. In women, reference values and ranges for the V(MCA)/V(ICA) index were as follows, by group: I, 1.82 (range, 0.88-2.68); II, 1.91 (range, 0.94-2.88); and III, 2.06 (range, 0.59-3.53). Respective values for men were as follows, by group: I, 2.10 (range, 0.96-3.24); II, 2.04 (range, 0.71-3.37); and III, 1.78 (range, 0.81-2.75). In subjects <40 years, the V(MCA)/V(ICA) index was significantly higher in men than in women. CONCLUSION: The V(MCA)/V(ICA) index significantly varies with age and sex. Sonographic diagnosis of cerebral vasospasm should be based on age- and sex-adjusted reference values of the V(MCA)/V(ICA) index.