In aphasia literature, it has been considered that a speech repetition defect represents the main constituent of conduction aphasia. Conduction aphasia has frequently been interpreted as a language impairment due to lesions of the arcuate fasciculus (AF) that disconnect receptive language areas from expressive ones. Modern neuroradiological studies suggest that the AF connects posterior receptive areas with premotor/motor areas, and not with Broca's area. Some clinical and neurophysiological findings challenge the role of the AF in language transferring. Unusual cases of inter-hemispheric dissociation of language lateralization (e.g. Broca's area in the left, and Wernicke's area in the right hemisphere) have been reported without evident repetition defects; electrocortical studies have found that the AF not only transmits information from temporal to frontal areas, but also in the opposite direction; transferring of speech information from the temporal to the frontal lobe utilizes two different streams and conduction aphasia can be found in cases of cortical damage without subcortical extension. Taken altogether, these findings may suggest that the AF is not required for repetition although could have a subsidiary role in it. A new language network model is proposed, emphasizing that the AF connects posterior brain areas with Broca's area via a relay station in the premotor/motor areas.

The interest in understanding how language is "localized" in the brain has existed for centuries. Departing from seven meta-analytic studies of functional magnetic resonance imaging activity during the performance of different language activities, it is proposed here that there are two different language networks in the brain: first, a language reception/understanding system, including a "core Wernicke's area" involved in word recognition (BA21, BA22, BA41, and BA42), and a fringe or peripheral area ("extended Wernicke's area:" BA20, BA37, BA38, BA39, and BA40) involved in language associations (associating words with other information); second, a language production system ("Broca's complex:" BA44, BA45, and also BA46, BA47, partially BA6-mainly its mesial supplementary motor area-and extending toward the basal ganglia and the thalamus). This paper additionally proposes that the insula (BA13) plays a certain coordinating role in interconnecting these two brain language systems.

We are proposing that, in the future, tests included in psychological and neuropsychological batteries should fulfil the following criteria. (1) Have a large enough normative database (“normative criterion”). Performance of subjects of different ages and different educational levels, including illiterates, should be well established. Normative data from different countries and cultural contexts should be available. (2) Know the effects of brain damage on different characteristics on the test (“clinical criterion”). (3) Know how the brain is activated when the test is performed (“experimental criterion”). (4) Know how this test correlates with other cognitive tests (“psychometric criterion”). Few contemporary tests fulfil all these criteria. A notable exception is Semantic Verbal Fluency test using the category ANIMALS. This test requires the generation of words corresponding to a specific semantic category, such as animals, fruits, vegetables, etc. Typically, the number of correct words produced in 1 minute is counted. Semantic verbal fluency taps lexical knowledge and semantic memory organization. Using regional cerebral blood flow measures, it has been reported that both frontal and temporal activation are observed while performing this test. Optimal fluency performance involves generating words within a subcategory and, when a subcategory is exhausted, switching to a new subcategory. Although different semantic categories have been used in this test, ANIMALS is the most frequent due to some significant advantages: (1) it is a clear enough semantic category across languages and cultures; (2) it is a relatively easy semantic category with only minor differences among people living in different countries, different educational systems, or belonging to different generations; and (3) it is an easy‐to‐administer, short, and common test included in different neuropsychological test batteries. It is concluded that obtaining similar information for other cognitive tests represents a huge research endeavour for psychology and neuropsychology during the 21st century.

The field of the neurobiology of language is experiencing a paradigm shift in which the predominant Broca-Wernicke-Geschwind language model is being revised in favor of models that acknowledge that language is processed within a distributed cortical and subcortical system. While it is important to identify the brain regions that are part of this system, it is equally important to establish the anatomical connectivity supporting their functional interactions. The most promising framework moving forward is one in which language is processed via two interacting "streams"--a dorsal and ventral stream--anchored by long association fiber pathways, namely the superior longitudinal fasciculus/arcuate fasciculus, uncinate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and two less well-established pathways, the middle longitudinal fasciculus and extreme capsule. In this article, we review the most up-to-date literature on the anatomical connectivity and function of these pathways. We also review and emphasize the importance of the often overlooked cortico-subcortical connectivity for speech via the "motor stream" and associated fiber systems, including a recently identified cortical association tract, the frontal aslant tract. These pathways anchor the distributed cortical and subcortical systems that implement speech and language in the human brain.

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Objective: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. Methods: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. Results: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). Interpretation: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753 N early one-third of children with epilepsy are refractory to medications. 1,2 Persistent seizures are associated with mortality, disability, psychosocial isolation, and diminished quality of life. 3-6 Vagus nerve stimulation (VNS) is an effective, safe, and well-tolerated intervention for a subset of patients with treatment-resistant epilepsy. 7-10 Although the goal of VNS is not complete resolution of seizures, many children will show a significant reduction in seizure frequency, as well as a reduction in hospitalizations and psychosocial comorbidities. 11,12 View this article online at wileyonlinelibrary.com.

Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5–21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.

To study the neural networks reorganization in pediatric epilepsy, a consortium of imaging centers was established to collect functional imaging data. Common paradigms and similar acquisition parameters were used. We studied 122 children (64 control and 58 LRE patients) across five sites using EPI BOLD fMRI and an auditory description decision task. After normalization to the MNI atlas, activation maps generated by FSL were separated into three sub-groups using a distance method in the principal component analysis (PCA)-based decisional space. Three activation patterns were identified: (1) the typical distributed network expected for task in left inferior frontal gyrus (Broca’s) and along left superior temporal gyrus (Wernicke’s) (60 controls, 35 patients); (2) a variant left dominant pattern with greater activation in IFG, mesial left frontal lobe, and right cerebellum (three controls, 15 patients); and (3) activation in the right counterparts of the first pattern in Broca’s area (one control, eight patients). Patients were over represented in Groups 2 and 3 (P < 0.0004). There were no scanner (P = 0.4) or site effects (P = 0.6). Our data-driven method for fMRI activation pattern separation is independent of a priori notions and bias inherent in region of interest and visual analyses. In addition to the anticipated atypical right dominant activation pattern, a sub-pattern was identified that involved intensity and extent differences of activation within the distributed left hemisphere language processing network. These findings suggest a different, perhaps less efficient, cognitive strategy for LRE group to perform the task.