Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children.

OBJECTIVES: The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC). METHODS: Participants were 27 children with AgCC and 32 TD children 8-16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure. RESULTS: The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC. CONCLUSIONS: This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.

Preventing Children From Developing Dyslexia: A Premature Writing Hypothesis.

It has been argued that dyslexia may develop in strongly left eye dominant children through learning to write using ipsilateral, right hemisphere motor pathways. New light on this theory has been cast by recent findings of atypical enhanced corpus callosum white matter in children with dyslexia, reflecting right to left hemisphere communication that is resistant to intensive remedial reading intervention. Enhanced corpus callosum white matter is consistent with uninhibited right to left hemisphere ipsilateral mirror-motor innervation, manifested as frequent mirror-letter writing errors in children with dyslexia. Delaying writing instruction until 7-8 years of age may prevent these errors and as well as the development of dyslexia. During the 7-8-year age period, visual-proprioceptive integration enables a child to mentally map whole word visual images onto kinesthetic/proprioceptive letter engrams (memory representations). Hypothetically, this process is facilitated by anterior commissure activity involving interhemispheric transfer of ipsilateral mirror-to-non mirror-motor movement. This postulate, involving delayed writing instruction pending further maturation, also receives indirect support from the remarkable proficiency leap among second graders reading Hebrew as Hebrew involves a leftward orthography in which ipsilateral right to left hemisphere innervation is uninhibited. Additionally, and more directly, normal reading comprehension for learning English among children with agenesis of the corpus callosum suggests that letter-sound decoding is not the sole route to proficient reading comprehension. In this paper, I make recommendations for obtaining empirical evidence of premature writing as a cause of dyslexia.

Large-scale functional network dynamics in human callosal agenesis: Increased subcortical involvement and preserved laterality.

In the human brain, the corpus callosum is the major white-matter commissural tract enabling the transmission of sensory-motor, and higher level cognitive information between homotopic regions of the two cerebral hemispheres. Despite developmental absence (i.e., agenesis) of the corpus callosum (AgCC), functional connectivity is preserved, including interhemispheric connectivity. Subcortical structures have been hypothesised to provide alternative pathways to enable this preservation. To test this hypothesis, we used functional Magnetic Resonance Imaging (fMRI) recordings in children with AgCC and typically developing children, and a time-resolved approach to retrieve temporal characteristics of whole-brain functional networks. We observed an increased engagement of the cerebellum and amygdala/hippocampus networks in children with AgCC compared to typically developing children. There was little evidence that laterality of activation networks was affected in AgCC. Our findings support the hypothesis that subcortical structures play an essential role in the functional reconfiguration of the brain in the absence of a corpus callosum.

Bilateral epileptic networks in congenital and acquired corpus callosum defects: EEG-fMRI study.

OBJECTIVES: Electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) allows imaging of brain-wide epileptic networks, and demonstrates that focal interictal epileptic activity is sometimes accompanied by bilateral functional activations. The corpus callosum (CC) facilitates bilateral spread of epileptic activity and at times targeted surgically for drug-resistant epilepsy (DRE). We hypothesized that focal epileptic networks are more unilateral in patients lacking intact CC. METHODS: We included focal DRE patients who underwent pre-surgical EEG-fMRI and had CC agenesis (group A, n = 5), patients who previously underwent anterior callosotomy as treatment for drop attacks and continued having seizures (group B, n = 6), and control group of patients with focal epilepsy and intact CC (group C, n = 9). Blood-oxygenation-level-dependent (BOLD) signal maps were generated for interictal epileptic discharges. To quantify bi-hemispheric distribution of epileptic networks, laterality indices were compared between groups. Anatomical and diffusion-weighted imaging demonstrated white matter pathways. RESULTS: 96% of studies demonstrated bilateral activations. Laterality indices were similar in groups A and C, whereas group B demonstrated a more bilateral network than group C (p = 0.028). Diffusion-weighted and anatomical imaging showed aberrant white matter pathways and larger anterior commissure in groups A and B. 68% of studies showed maximal activation cluster concordant with the presumed epileptic focus, 28% showed non-maximal activation at presumed focus. SIGNIFICANCE: Focal epileptic activity is associated with bilateral functional activations despite lack of intact CC, and is associated with stronger contralateral activation in patients after anterior callosotomy compared to controls. These findings disprove our initial hypothesis, and combined with white matter structural imaging, may indicate that the CC is not a sole route of propagation of epileptic activity, which might spread via anterior commissure. Our study demonstrates the utility of EEG-fMRI in assessing epileptic networks and potentially aiding in tailoring surgical treatments in DRE patients with callosal anomalies, and in callosal surgeries.

The Prenatal Morphomechanic Impact of Agenesis of the Corpus Callosum on Human Brain Structure and Asymmetry.

Genetic, molecular, and physical forces together impact brain morphogenesis. The early impact of deficient midline crossing in agenesis of the Corpus Callosum (ACC) on prenatal human brain development and architecture is widely unknown. Here we analyze the changes of brain structure in 46 fetuses with ACC in vivo to identify their deviations from normal development. Cases of complete ACC show an increase in the thickness of the cerebral wall in the frontomedial regions and a reduction in the temporal, insular, medial occipital and lateral parietal regions, already present at midgestation. ACC is associated with a more symmetric configuration of the temporal lobes and increased frequency of atypical asymmetry patterns, indicating an early morphomechanic effect of callosal growth on human brain development affecting the thickness of the pallium along a ventro-dorsal gradient. Altered prenatal brain architecture in ACC emphasizes the importance of conformational forces introduced by emerging interhemispheric connectivity on the establishment of polygenically determined brain asymmetries.

Improved neurodevelopmental prognostication in isolated corpus callosal agenesis: fetal magnetic resonance imaging-based scoring system.

OBJECTIVES: Corpus callosal agenesis (CCA) is one of the most common brain malformations and is generally associated with a good outcome when isolated. However, up to 25% of patients are at risk of neurodevelopmental delay, which currently available clinical and imaging parameters are inadequate to predict. The objectives of this study were to apply and validate a fetal magnetic resonance imaging (MRI) anatomical scoring system in a cohort of fetuses with isolated CCA and to evaluate the correlation with postnatal neurodevelopmental outcome. METHODS: This was a retrospective cohort study of cases of prenatally diagnosed isolated CCA (as determined on ultrasound and MRI), with normal karyotype and with known postnatal neurodevelopmental outcome assessed by standardized testing. A fetal brain MRI anatomical scoring system based on seven categories (gyration, opercularization, temporal lobe symmetry, lamination, hippocampal position, basal ganglia and ventricular size) was developed and applied to the cohort; a total score of 0-11 points could be given, with a score of 0 representing normal anatomy. Images were scored independently by two neuroradiologists blinded to the outcome. For the purpose of assessing the correlation between fetal MRI score and neurodevelopmental outcome, neurodevelopmental test results were scored as follows: 0, 'below average' (poor outcome); 1, 'average'; and 2, 'above average' (good outcome). Spearman's rank coefficient was used to assess correlation, and inter-rater agreement in the assessment of fetal MRI score was calculated. RESULTS: Twenty-one children (nine females (42.9%)) fulfilled the inclusion criteria. Thirty-seven fetal MRI examinations were evaluated. Mean gestational age was 28.3 ± 4.7 weeks (range, 20-38 weeks). All fetuses were delivered after 35 weeks' gestation with no perinatal complications. Fetal MRI scores ranged from 0 to 6 points, with a median of 3 points. Inter-rater agreement in fetal MRI score assessment was excellent (intraclass correlation coefficient, 0.959 (95% CI, 0.921-0.979)). Neurodevelopmental evaluation was performed on average at 2.6 ± 1.46 years (range, 0.5-5.8 years). There was a significant negative correlation between fetal MRI score and neurodevelopmental outcome score in the three areas tested: cognitive (ρ = -0.559, P < 0.0001); motor (ρ = -0.414, P = 0.012) and language (ρ = -0.565, P < 0.0001) skills. Using fetal MRI score cut-offs of ≤ 3 (good outcome) and ≥ 4 points (high risk for poor outcome), the correct prognosis could be determined in 20/21 (95.2% (95% CI, 77.3-99.2%)) cases. CONCLUSION: By assessing structural features of the fetal brain on MRI, it may be possible to better stratify prenatally the risk of poor neurodevelopmental outcome in CCA patients. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Structural Neuroplastic Responses Preserve Functional Connectivity and Neurobehavioural Outcomes in Children Born Without Corpus Callosum.

The corpus callosum is the largest white matter pathway in the brain connecting the two hemispheres. In the context of developmental absence (agenesis) of the corpus callosum (AgCC), a proposed candidate for neuroplastic response is strengthening of intrahemispheric pathways. To test this hypothesis, we assessed structural and functional connectivity in a uniquely large cohort of children with AgCC (n = 20) compared with typically developing controls (TDC, n = 29), and then examined associations with neurobehavioral outcomes using a multivariate data-driven approach (partial least squares correlation, PLSC). For structural connectivity, children with AgCC showed a significant increase in intrahemispheric connectivity in addition to a significant decrease in interhemispheric connectivity compared with TDC, in line with the aforementioned hypothesis. In contrast, for functional connectivity, children with AgCC and TDC showed a similar pattern of intrahemispheric and interhemispheric connectivity. In conclusion, we observed structural strengthening of intrahemispheric pathways in children born without corpus callosum, which seems to allow for functional connectivity comparable to a typically developing brain, and were relevant to explain neurobehavioral outcomes in this population. This neuroplasticity might be relevant to other disorders of axonal guidance, and developmental disorders in which corpus callosum alteration is observed.

Aicardi syndrome with peripapillary staphyloma: A case report and review of literature

@#<p style="text-align: justify;">Aicardi Syndrome (AS) is a rare X-linked congenital disorder traditionally characterized by a triad of dysgenesis of corpus callosum, seizures, and chorioretinal abnormalities. Patients often have severe psychomotor delay and shortened life expectancy. However, Aicardi syndrome is a clinically heterogeneous disorder. We present a case of a 14-year-old with the traditional triad of history of infantile spasm, complete agenesis of the corpus callosum, and chorioretinal abnormality but with peripapillary staphyloma and with no psychomotor delays. Based on the review of literature, this is the first reported case of AS in the Philippines, the first reported case of AS with peripapillary staphyloma, and is one of the 3 reported cases of AS with normal psychomotor development. There remains no factor that can prognosticate cognitive function in AS at present including genetic testing.</p>

Microphthalmia, Linear Skin Defects, Callosal Agenesis, and Cleft Palate in a Patient with Deletion at Xp22.3p22.2.

The authors describe the clinical findings observed in a Brazilian girl that are suggestive of microphthalmia and linear skin defects (MLS) also known as MIDAS syndrome (OMIM #309801). She also presented with short stature, agenesis of corpus callosum, cleft palate, enamel defects, and genitourinary anomalies, which are rarely reported within the clinical spectrum of MLS. The 11,5 Mb deletion in Xp22.3p22.2 observed in the patient includes the entire HCCS gene (responsible for the MLS phenotype) and also encompasses several other genes involved with behavioral phenotypes, craniofacial and central nervous system development such as MID1, NLGN4X, AMELX , ARHGAP6, and TBL1X. The whole clinical features of our proband possibly represents an unusual MLS syndromic phenotype caused by an Xp22.3p22.2 continuous gene deletion.

The neuroimaging findings of monocarboxylate transporter 1 deficiency.

Monocarboxylate transporter 1 (MCT1) deficiency was first described in 2014 by Hasselt et al. as a novel genetic cause of recurrent ketoacidosis. Patients present in the first year of life with acute episodes of ketoacidosis triggered by fasting or infections. Patients with homozygous mutations are known to have a more severe phenotype with mild to moderate developmental delay and an increased prevalence of epilepsy. There is only one recent report of the neuroimaging findings of this disorder as reported by Al-Khawaga et al. (Front Pediatr. 7:299, 2019). We report the neuroimaging abnormalities in two siblings with similar clinical presentation of recurrent ketoacidosis, seizures, and developmental delay. Whole exome sequencing in the younger sibling confirmed a known pathogenic homozygous mutation in MCT1, also known as SLC16A1 gene. Brain MRI showed a similar very distinctive pattern of signal abnormality at the gray-white matter junction, basal ganglia, and thalami in both patients. Both siblings had agenesis of the corpus callosum. Knowledge of this pattern of brain involvement might contribute to an earlier diagnosis and timely management of this rare and under recognized disorder.

A Pericallosal Lipoma Case with Abnormal Vasculature Mimicking Arteriovenous Malformation.

Pericallosal lipomas (PCLs) are rare tumors of the central nervous system. They may be associated with some parenchymal and vascular anomalies of brain. Magnetic resonance imaging is the modality of choice to assess the extent of the PCLs and possible concomitant malformations such as callosal agenesis/disgenesis. Computerized tomography angiography may be indicated to evaluate the vasculature of the lesion. We report here a case of PCL with rare features including asymptomatic callosal agenesis, bilateral choroid plexus lipomas and abnormal vasculature.

Cortical lateralization of cheirosensory processing in callosal dysgenesis.

The paradoxical absence of a split-brain syndrome in most cases of callosal dysgenesis has originated three main hypotheses, namely, (i) bilateral cortical representation of language, (ii) bilateral thalamocortical projections of somatosensory pathways conveyed by the spinothalamic-medial lemniscus system, and (iii) a variable combination of (i) and (ii). We used functional neuroimaging to investigate the cortical representation and lateralization of somatosensory information from the palm of each hand in six cases of callosal dysgenesis (hypothesis [ii]). Cortical regions of interest were contralateral and ipsilateral S1 (areas 3a and 3b, 1 and 2 in the central sulcus and postcentral gyrus) and S2 (parts of areas 40 and 43 in the parietal operculum). The degree of cortical asymmetry was expressed by a laterality index (LI), which may assume values from -1 (fully left-lateralized) to +1 (fully right-lateralized). In callosal dysgenesis, LI values for the right and the left hands were, respectively, -1 and + 1 for both S1 and S2, indicating absence of engagement of ipsilateral S1 and S2. In controls, LI values were - 0.70 (S1) and - 0.51 (S2) for right hand stimulation, and 0.82 (S1) and 0.36 (S2) for left hand stimulation, reflecting bilateral asymmetric activations, which were significantly higher in the hemisphere contralateral to the stimulated hand. Therefore, none of the main hypotheses so far entertained to account for the callosal dysgenesis-split-brain paradox have succeeded. We conclude that the preserved interhemispheric transfer of somatosensory tactile information in callosal dysgenesis must be mediated by a fourth alternative, such as aberrant interhemispheric bundles, reorganization of subcortical commissures, or both.

Septo-optic Dysplasia : Assessment of Associated Findings with Special Attention to the Olfactory Sulci and Tracts.

PURPOSE: Septo-optic dysplasia is a congenital disorder consisting of optic nerve hypoplasia and absent septum pellucidum. While associated anomalies have been described, olfactory sulcus and bulb-tract hypoplasia have been scantily reported and was the focus of this study. METHODS: The picture archival and communications system and radiology information system (PACS-RIS) was searched over 15 years for patients with suspected septo-optic dysplasia (n = 41) and cerebral magnetic resonance imaging (MRI). Included patients had coronal (≤3 mm), axial (≤4 mm), and sagittal (≤4 mm) imaging reviewed by two staff neuroradiologists by consensus. Both olfactory sulcus and bulb-tract hypoplasia were ascribed a grade of 0 (normal) to 3 (complete hypoplasia). Other associated congenital anomalies were recorded, if present. Incidence of anomalies were compared to age-matched and gender-matched control patients. RESULTS: Out of 41 septo-optic dysplasia patients 33 were included (mean age = 120.7 months), with 8 excluded due to isolated septum pellucidum absence (n = 5), isolated bilateral optic hypoplasia (n = 2), or inadequate imaging (n = 1). An olfactory sulcus was hypoplastic on one or both sides in 14/33 (42.4%). Olfactory bulb hypoplasia was noted in one or both tracts in 15/33 (45.4%). A significant correlation was found between degree of olfactory sulcal and bulb-tract hypoplasia (ρ = 0.528, p = 0.0009). Other anomalies were: anterior falx dysplasia (n = 16, 48.5%), incomplete hippocampal inversion (n = 14, 42.4%), polymicrogyria (n = 11, 33.3%), callosal complete or partial agenesis (n = 10, 30.3%), schizencephaly (n = 8, 24.2%), ectopic posterior pituitary (n = 6, 18.2%), and nodular heterotopia (n = 4, 12.1%). Of the age-matched control patients 10/33 (30.3%) had at least mild anterior falx hypoplasia, and 1 control patient was noted to have unilateral incomplete hippocampal inversion (IHI); none of the age-matched control patients had olfactory sulcus or bulb-tract hypoplasia. CONCLUSION: Olfactory sulcus and bulb-tract hypoplasia are fairly common in septo-optic dysplasia and can be discordant between sides. Of the other associated anomalies, anterior falx dysplasia seems to be the most common.

[Agenesis of the corpus callosum]. / Balkenfehlbildungen.

CLINICAL ISSUE: Agenesis of the corpus callosum is reported to have an incidence of about 1:4000 live births. In 30-45% of cases, genetic etiologies can be identified, e. g., 10% chromosomal anomalies and 20-35% genetic syndromes. Environmental factors like fetal alcohol syndrome are also known to be prone to callosal agenesis. Callosal agenesis can be complete or partial and can be isolated or associated with other central nervous system (CNS) anomalies (e. g., cortical developmental disorders, callosal lipoma, intracranial cysts) or extra-CNS anomalies (e. g., eyes, face, cardiovascular). STANDARD RADIOLOGICAL METHODS AND METHODICAL INNOVATIONS: Diagnosis is made using ultrasound, computed tomography (CT) or best with magnetic resonance imaging (MRI). Typical imaging findings in callosal agenesis are colpocephaly, high riding enlarged third ventricle, Texas Longhorn configuration of frontal horns and so-called Probst bundles parasagittal. Diffusion tensor imaging and fiber-tracking, based on diffusion-weighted techniques, can also visualize fiber/tract anomalies in the patients' brains. ASSESSMENT: Clinical correlations of callosal agenesis is difficult in general because of the common association of other CNS malformations. Differential diagnosis of primary complete or partial callosal agenesis are secondary callosal changes, e. g. vascular, inflammatory or posttreatment in origin.

EPG5-Related Vici Syndrome: A Primary Defect of Autophagic Regulation with an Emerging Phenotype Overlapping with Mitochondrial Disorders.

Vici syndrome is a rare, under-recognised, relentlessly progressive congenital multisystem disorder characterised by five principal features of callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and oculocutaneous hypopigmentation. In addition, three equally consistent features (profound developmental delay, progressive failure to thrive and acquired microcephaly) are highly supportive of the diagnosis. Since its recognition as a distinct entity in 1988, an extended phenotype with sensorineural hearing loss, skeletal myopathy and variable involvement of virtually any organ system, including the lungs, thyroid, liver and kidneys, have been described.Autosomal recessive mutations in EPG5 encoding ectopic P-granules autophagy protein 5 (EPG5), a key autophagy regulator implicated in the formation of autolysosomes, were identified as the genetic cause of Vici syndrome. The eight key features outlined above are highly predictive of EPG5 involvement, with pathogenic EPG5 mutations identified in >90% of cases where six or more of these features are present. The manifestation of all eight features has a specificity of 97% and sensitivity of 89% for EPG5-related Vici syndrome. Nevertheless, substantial clinical overlap exists with other multisystem disorders, in particular congenital disorders of glycosylation and mitochondrial disorders. Clinical and pathological findings suggest Vici syndrome as a paradigm of congenital disorders of autophagy, a novel group of inherited neurometabolic conditions linking neurodevelopment and neurodegeneration due to primary autophagy defects.Here we describe the diagnostic odyssey in a 4-year-old boy whose clinical presentation with multisystem manifestations including skeletal myopathy mimicked a mitochondrial disorder. A genetic diagnosis of Vici syndrome was made through whole genome sequencing which identified compound heterozygous variants in EPG5. We also review the myopathic presentation and morphological characterisation of previously reported cases.

Semilobarholoprosencephaly - A Dreading Congenital Anomaly.

Holoprosencephaly (HPE) is a group of structural abnormalities of brain that is an important cause of childhood mortality and morbidity. They usually occur due to impaired midline cleavage of embryonic forebrain i.e., failure of differentiation of the prosencephalon into the telecephalon and diencephalon. De Myer classified this anomaly ranging from alobar to semilobar and lobar type. It can be associated with microcephaly and midline facial anomalies. We present a case of semilobar holoprosencephaly with corpus callosal agenesis.

Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum.

The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.

Fetal development of the corpus callosum: Insights from a 3T DTI and tractography study in a patient with segmental callosal agenesis.

Commissural embryology mechanisms are not yet completely understood. The study and comprehension of callosal dysgenesis can provide remarkable insights into embryonic or fetal commissural development. The diffusion tensor imaging (DTI) technique allows the in vivo analyses of the white-matter microstructure and is a valid tool to clarify the disturbances of brain connections in patients with dysgenesis of the corpus callosum (CC). The segmental callosal agenesis (SCAG) is a rare partial agenesis of the corpus callosum (ACC). In a newborn with SCAG the DTI and tractography analyses proved that the CC was made of two separate segments consisting respectively of the ventral part in the genu and body of the CC, connecting the frontal lobes, and the dorsal part in the CC splenium and the attached hippocampal commissure (HC), connecting the parietal lobes and the fornix. These findings support the embryological thesis of a separated origin of the ventral and the dorsal parts of the CC.

Proverb comprehension in individuals with agenesis of the corpus callosum.

Comprehension of non-literal language involves multiple neural systems likely involving callosal connections. We describe proverb comprehension impairments in individuals with isolated agenesis of the corpus callosum (AgCC) and normal-range general intelligence. Experiment 1 compared Gorham Proverb Test (Gorham, 1956) performance in 19 adults with AgCC and 33 neurotypical control participants of similar age, sex, and intelligence. Experiment 2 used the Proverbs subtest of the Delis-Kaplan Executive Function System (D-KEFS, 2001) to compare 19 adults with AgCC and 17 control participants with similar age, sex, and intelligence. Gorham Proverbs performance was impaired in the AgCC group for both the free-response and multiple-choice tasks. On the D-KEFS proverbs test, the AgCC group performed significantly worse on the free-response task (and all derivative scores) despite normal levels of performance on the multiple-choice task. Covarying verbal intelligence did not alter these outcomes. However, covarying a measure of non-literal language comprehension considerably reduced group differences in proverb comprehension on the Gorham test, but had little effect on the D-KEFS group differences. The difference between groups seemed to be greatest when participants had to generate their own interpretation (free response), or in the multiple choice format when the test included many proverbs that were likely to be less familiar. Taken together, the results of this study clearly show that proverb comprehension is diminished in individuals with AgCC compared to their peers.

Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia.

Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called "split-brain"). In this form of alien hand syndrome, one hand acts at cross purposes with the other "against the patient's will". Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant information on the evolution of behavioral syndromes in addition to that provided by structural and task-based functional imaging.