Intrahemispheric Connectivity Research Articles

Idiosyncratic patterns of interhemispheric connectivity in the face and scene networks of the human brain

Abstract Neuroimaging studies have revealed a network of regions in both hemispheres of the human brain that respond selectively to faces. Neural models of face processing have typically focused on functional connectivity between regions in the same hemisphere (intrahemispheric), with a particular bias toward the right hemisphere. Here, we explored the role of interhemispheric connectivity using fMRI. We used three datasets to compare functional connectivity, as shown by correlations between the time-courses of neural activity of face regions during different natural viewing paradigms. We found higher correlations of neural activity between corresponding interhemispheric regions (e.g., rFFA–lFFA) than between intrahemispheric regions (e.g., rFFA–rOFA), indicating a bias towards higher interhemispheric than intrahemispheric connectivity. A similar interhemispheric bias was evident in scene-selective regions. In contrast, we did not find an interhemispheric bias in early visual regions (V1–V3), where intrahemispheric connectivity between corresponding regions was generally higher than interhemispheric connectivity. Next, we asked whether the higher interhemispheric connectivity in the face and scene networks between corresponding regions was consistent across participants. We found that the interhemispheric bias was significantly attenuated when we compared the time-course of response across participants. This shows that interhemispheric bias in connectivity between corresponding regions in the face and scene networks is specific to the individual. These findings raise the possibility that idiosyncratic variation in interhemispheric connectivity may explain individual differences in perception.

Deleterious effect of sustained neuroinflammation in pediatric traumatic brain injury

IntroductionDespite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model. MethodsPediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45. ResultsTBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors. ConclusionsWe show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI.

Coherent activity within and between hemispheres: cortico-cortical connectivity revealed by rTMS of the right posterior parietal cortex.

Low frequency (1 Hz) repetitive transcranial stimulation (rTMS) applied over right posterior parietal cortex (rPPC) has been shown to reduce cortical excitability both of the stimulated area and of the interconnected contralateral homologous areas. In the present study, we investigated the whole pattern of intra- and inter-hemispheric cortico-cortical connectivity changes induced by rTMS over rPPC. To do so, 14 healthy participants underwent resting state EEG recording before and after 30 min of rTMS at 1 Hz or sham stimulation over the rPPC (electrode position P6). Real stimulation was applied at 90% of motor threshold. Coherence values were computed on the electrodes nearby the stimulated site (i.e., P4, P8, and CP6) considering all possible inter- and intra-hemispheric combinations for the following frequency bands: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-50 Hz). Results revealed a significant increase in coherence in delta, theta, alpha and beta frequency bands between rPPC and the contralateral homologous sites. Moreover, an increase in coherence in theta, alpha, beta and gamma frequency bands was found between rPPC and right frontal sites, reflecting the activation of the fronto-parietal network within the right hemisphere. Summarizing, subthreshold rTMS over rPPC revealed cortico-cortical inter- and intra-hemispheric connectivity as measured by the increase in coherence among these areas. Moreover, the present results further confirm previous evidence indicating that the increase of coherence values is related to intra- and inter-hemispheric inhibitory effects of rTMS. These results can have implications for devising evidence-based rehabilitation protocols after stroke.

Altered whole-brain functional network in patients with frontal low-grade gliomas: a resting-state functional MRI study.

Gliomas are the most common primary brain tumor. Currently, topological alterations of whole-brain functional network caused by gliomas are not fully understood. The work here clarified the topological reorganization of the functional network in patients with unilateral frontal low-grade gliomas (LGGs). A total of 45 patients with left frontal LGGs, 19 with right frontal LGGs, and 25 healthy controls (HCs) were enrolled. All the resting-state functional MRI (rs-fMRI) images of the subjects were preprocessed to construct the functional network matrix, which was used for graph theoretical analysis. A two-sample t-test was conducted to clarify the differences in global and nodal network metrics between patients and HCs. A network-based statistic approach was used to identify the altered specific pairs of regions in which functional connectivity in patients with LGGs. The local efficiency, clustering coefficient, characteristic path length, and normalized characteristic path length of patients with unilateral frontal LGGs were significantly lower than HCs, while there were no significant differences of global efficiency and small-worldness between patients and HCs. Compared with the HCs, betweenness centrality, degree centrality, and nodal efficiency of several brain nodes were changed significantly in patients. Around the tumor and its adjacent areas, the inter- and intra-hemispheric connections were significantly decreased in patients with left frontal LGGs. The patients with unilateral frontal LGGs have altered global and nodal network metrics and decreased inter- and intra-hemispheric connectivity. These topological alterations may be involved in functional impairment and compensation of patients.

QEEG findings in nonsyndromic sagittal craniosynostosis

Despite the undertaken treatment, children with nonsyndromic sagittal craniosynostosis (NSC) are burdened with problems with speech development, visuospatial and other cognitive deficits. The electroencephalographic assessment has not influenced the diagnostics and treatment strategy of craniosynostosis so far but the introduction of quantitative EEG (QEEG) protocols renewed an interest in the functional aspect of this disease. In this study we retrospectively assessed the QEEG records of 25 children with NSC aged 1–18 months (mean age 9.62 months) before and after surgery. In each case, the amplitude, interhemispheric (ICoh) and intrahemispheric (HCoh) coherence indices were calculated. Obtained data were compared to age-matched control group of 25 normocephalic children. Children with NSC presented significantly lower values of amplitudes and intrahemispheric coherence in occipital, posterior parietal and posterior temporal regions than normocephalic children. The values of amplitudes, ICoh and HCoh in pre- and postoperative QEEG records mostly remained unchanged, with a slight improvement in HCoh in centro-parietal area. These findings suggest that NSC children present their own QEEG profile. The operative treatment improves an intrahemispheric connectivity, but there still exists a significant difference in the occipitotemporal, frontotemporal and centro-frontal areas, which may be considered as a functional substrate of reported speech and neurocognitive problems. QEEG findings in nonsyndromic sagittal craniosynostosis.

Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity

Studying the development of brain network disruptions in epilepsy is challenged by the paucity of data before epilepsy onset. Here, we used the unilateral, kainate mouse model of hippocampal epilepsy to investigate brain network changes before and after epilepsy onset and their stability across time.Using 32 epicranial electrodes distributed over the mouse hemispheres, we analyzed EEG epochs free from epileptic activity in 15 animals before and 28 days after hippocampal injection (group 1) and in 20 animals on two consecutive days (d28 and d29, group 2). Statistical dependencies between electrodes were characterized with the debiased-weighted phase lag index. We analyzed: a) graph metric changes from baseline to chronic stage (d28) in group 1; b) their reliability across d28 and d29, in group 2; c) their correlation with epileptic activity (EA: seizure, spike and fast-ripple rates), averaged over d28 and d29, in group 2.During the chronic stage, intra-hemispheric connections of the non-injected hemisphere strengthened, yielding an asymmetrical network in low (4–8 Hz) and high theta (8–12 Hz) bands. The contralateral hemisphere also became more integrated and segregated within the high theta band. Both network topology and EEG markers of EA were stable over consecutive days but not correlated with each other.Altogether, we show reproducible large-scale network modifications after the development of focal epilepsy. These modifications are mostly specific to the non-injected hemisphere. The absence of correlation with epileptic activity does not allow to specifically ascribe these network changes to mechanisms supporting EA or rather compensatory inhibition but supports the notion that epilepsy extends beyond the sole repetition of EA and impacts network that might not be involved in EA generation.

Inter- and Intra- Hemispheric Interactions in Reading Ambiguous Words

The present study investigated how the brain processes words with multiple meanings. Specifically, we examined the inter- and intra-hemispheric connectivity of unambiguous words compared to two types of ambiguous words: homophonic homographs, which have multiple meanings mapped to a single phonological representation and orthography, and heterophonic homographs, which have multiple meanings mapped to different phonological representations but the same orthography. Using a semantic relatedness judgment task and effective connectivity analysis via Dynamic Causal Modeling (DCM) on previously published fMRI data (Bitan et al., 2017), we found that the two hemispheres compete in orthographic processing during the reading of unambiguous words. For heterophonic homographs, we observed increased connectivity within the left hemisphere, highlighting the importance of top-down re-activation of orthographic representations by phonological ones for considering alternative meanings. For homophonic homographs, we found a flow of information from the left to the right hemisphere and from the right to the left, indicating that the brain retrieves different meanings using different pathways. These findings provide novel insights into the complex mechanisms involved in language processing and shed light on the different communication patterns within and between hemispheres during the processing of ambiguous and unambiguous words.

Globally altered microstructural properties and network topology in Rasmussen's encephalitis.

Rasmussen's encephalitis is an immune-mediated brain disorder characterised by progressive unilateral cerebral atrophy, neuroinflammation, drug-resistant seizures and cognitive decline. However, volumetric changes and epileptiform EEG activity were also observed in the contralateral hemisphere, raising questions about the aetiology of contralateral involvement. In this study, we aim to investigate alterations of white matter integrity, structural network topology and network efficiency in Rasmussen's encephalitis using diffusion-tensor imaging. Fourteen individuals with Rasmussen's encephalitis (11 female, median onset 6 years, range 4-22, median disease duration at MRI 5 years, range 0-42) and 20 healthy control subjects were included. All subjects underwent T1-weighted structural and diffusion-tensor imaging. Diffusion-tensor images were analysed using the fixel-based analysis framework included in the MRtrix3 toolbox. Fibre density and cross-section served as a quantitative measure for microstructural white matter integrity. T1-weighted structural images were processed using FreeSurfer, subcortical segmentations and cortical parcellations using the Desikan-Killiany atlas served as nodes in a structural network model, edge weights were determined based on streamline count between pairs of nodes and compared using network-based statistics. Global efficiency was used to quantify network integration on an intrahemispheric level. All metrics were compared cross-sectionally between individuals with Rasmussen's encephalitis and healthy control subjects using sex and age as regressors and within the Rasmussen's encephalitis group using linear regression including age at onset and disease duration as independent variables. Relative to healthy control subjects, individuals with Rasmussen's encephalitis showed significantly (family-wise-error-corrected P < 0.05) lower fibre density and cross-section as well as edge weights in intrahemispheric connections within the ipsilesional hemisphere and in interhemispheric connections. Lower edge weights were noted in the contralesional hemisphere and in interhemispheric connections, with the latter being mainly affected within the first 2 years after disease onset. With longer disease duration, fibre density and cross-section significantly (uncorrected P < 0.01) decreased in both hemispheres. In the contralesional corticospinal tract, fibre density and cross-section significantly (uncorrected P < 0.01) increased with disease duration. Intrahemispheric edge weights (uncorrected P < 0.01) and global efficiency significantly increased with disease duration in both hemispheres (ipsilesional r = 0.74, P = 0.001; contralesional r = 0.67, P = 0.012). Early disease onset was significantly (uncorrected P < 0.01) negatively correlated with lower fibre density and cross-section bilaterally. Our results show that the disease process of Rasmussen's encephalitis is not limited to the cortex of the lesioned hemisphere but should be regarded as a network disease affecting white matter across the entire brain and causing degenerative as well as compensatory changes on a network level.

Differential responses in the mirror neuron system during imitation of individual emotional facial expressions and association with autistic traits

The mirror neuron system (MNS), including the inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and superior temporal sulcus (STS) plays an important role in action representation and imitation and may be dysfunctional in autism spectrum disorder (ASD). However, it's not clear how these three regions respond and interact during the imitation of different basic facial expressions and whether the pattern of responses is influenced by autistic traits. Thus, we conducted a natural facial expression (happiness, angry, sadness and fear) imitation task in 100 healthy male subjects where expression intensity was measured using facial emotion recognition software (FaceReader) and MNS responses were recorded using functional near-infrared spectroscopy (fNIRS). Autistic traits were measured using the Autism Spectrum Quotient questionnaire. Results showed that imitation of happy expressions produced the highest expression intensity but a small deactivation in MNS responses, suggesting a lower processing requirement compared to other expressions. A cosine similarity analysis indicated a distinct pattern of MNS responses during imitation of each facial expression with functional intra-hemispheric connectivity between the left IPL and left STS being significantly higher during happy compared to other expressions, while inter-hemispheric connectivity between the left and right IPL differed between imitation of fearful and sad expressions. Furthermore, functional connectivity changes during imitation of each different expression could reliably predict autistic trait scores. Overall, the results provide evidence for distinct patterns of functional connectivity changes between MNS regions during imitation of different emotions which are also associated with autistic traits.

Compensatory mechanisms of reduced interhemispheric EEG connectivity during sleep in patients with apnea

We performed a mathematical analysis of functional connectivity in electroencephalography (EEG) of patients with obstructive sleep apnea (OSA) (N = 10; age: 52.8 ± 13 years; median age: 49 years; male/female ratio: 7/3), compared with a group of apparently healthy participants (N = 15; age: 51.5 ± 29.5 years; median age: 42 years; male/female ratio: 8/7), based on the calculation of wavelet bicoherence from nighttime polysomnograms. Having observed the previously known phenomenon of interhemispheric synchronization deterioration, we demonstrated a compensatory increase in intrahemispheric connectivity, as well as a slight increase in the connectivity of the central and occipital areas for high-frequency EEG activity. Significant changes in functional connectivity were extremely stable in groups of apparently healthy participants and OSA patients, maintaining the overall pattern when comparing different recording nights and various sleep stages. The maximum variability of the connectivity was observed at fast oscillatory processes during REM sleep. The possibility of observing some changes in functional connectivity of brain activity in OSA patients in a state of passive wakefulness opens up prospects for further research. Developing the methods of hypnogram evaluation that are independent of functional connectivity may be useful for implementing a medical decision support system.

Clinical and neuroimaging laboratory possibilities of diagnostics of vestibulo-atactic syndrome in patients with postmastectomic syndrome

Background. In recent years, the prognosis of survival after treatment for breast cancer (BC) has improved significantly, leading to an increase in the life expectancy of patients and the incidence of long-term side effects of therapy. reducing the risks of complications and developing a unified algorithm for diagnosing cerebral complications are necessary to improve the quality of life of patients.Objective. To correlate the CNS and endothelium damage biomarkers concentration and the functional connectivity of the brain in patients with newly diagnosed vestibulo-atactic syndrome (VAS) and without it in the late period of radical treatment of breast cancer.Design and methods. The study involved 21 patients with VAS in the late postoperative period after radical treatment of breast cancer, as well as a group of healthy volunteers — 17 people. Biomarkers were determined by ELISA. Functional MRI was performed.Results. An increase in markers of CNS damage and endothelial damage (ICAM, PECAM) was noted in patients with post-mastectomy syndrome (PMES) and VAS, compare with control group and PMES without VAS group. The processes of disorganization and the formation and strengthening of interand intrahemispheric connections were noted using fMRI.Conclusion. The development of novel diagnostics methods, including the use of fMRI and the determination of different biomarkers are promising for improvement of the VAS treatment effectiveness in patients with PMES.

Predicting depressed and elevated mood symptomatology in bipolar disorder using brain functional connectomes.

The study is aimed to identify brain functional connectomes predictive of depressed and elevated mood symptomatology in individuals with bipolar disorder (BD) using the machine learning approach Connectome-based Predictive Modeling (CPM). Functional magnetic resonance imaging data were obtained from 81 adults with BD while they performed an emotion processing task. CPM with 5000 permutations of leave-one-out cross-validation was applied to identify functional connectomes predictive of depressed and elevated mood symptom scores on the Hamilton Depression and Young Mania rating scales. The predictive ability of the identified connectomes was tested in an independent sample of 43 adults with BD. CPM predicted the severity of depressed [concordance between actual and predicted values (r = 0.23, pperm (permutation test) = 0.031) and elevated (r = 0.27, pperm = 0.01) mood. Functional connectivity of left dorsolateral prefrontal cortex and supplementary motor area nodes, with inter- and intra-hemispheric connections to other anterior and posterior cortical, limbic, motor, and cerebellar regions, predicted depressed mood severity. Connectivity of left fusiform and right visual association area nodes with inter- and intra-hemispheric connections to the motor, insular, limbic, and posterior cortices predicted elevated mood severity. These networks were predictive of mood symptomatology in the independent sample (r ⩾ 0.45, p = 0.002). This study identified distributed functional connectomes predictive of depressed and elevated mood severity in BD. Connectomes subserving emotional, cognitive, and psychomotor control predicted depressed mood severity, while those subserving emotional and social perceptual functions predicted elevated mood severity. Identification of these connectome networks may help inform the development of targeted treatments for mood symptoms.

Intra– and inter–hemispheric network dynamics supporting object recognition and speech production

We built normative brain atlases that animate millisecond-scale intra- and inter-hemispheric white matter-level connectivity dynamics supporting object recognition and speech production. We quantified electrocorticographic modulations during three naming tasks using event-related high-gamma activity from 1,114 nonepileptogenic intracranial electrodes (i.e., non-lesional areas unaffected by epileptiform discharges). Using this electrocorticography data, we visualized functional connectivity modulations defined as significant naming-related high-gamma modulations occurring simultaneously at two sites connected by direct white matter streamlines on diffusion-weighted imaging tractography. Immediately after stimulus onset, intra- and inter-hemispheric functional connectivity enhancements were confined mainly across modality-specific perceptual regions. During response preparation, left intra-hemispheric connectivity enhancements propagated in a posterior-to-anterior direction, involving the left precentral and prefrontal areas. After overt response onset, inter- and intra-hemispheric connectivity enhancements mainly encompassed precentral, postcentral, and superior-temporal (STG) gyri. We found task-specific connectivity enhancements during response preparation as follows. Picture naming enhanced activity along the left arcuate fasciculus between the inferior-temporal and precentral/posterior inferior-frontal (pIFG) gyri. Nonspeech environmental sound naming augmented functional connectivity via the left inferior longitudinal and fronto-occipital fasciculi between the medial-occipital and STG/pIFG. Auditory descriptive naming task enhanced usage of the left frontal U-fibers, involving the middle-frontal gyrus. Taken together, the commonly observed network enhancements include inter-hemispheric connectivity optimizing perceptual processing exerted in each hemisphere, left intra-hemispheric connectivity supporting semantic and lexical processing, and inter-hemispheric connectivity for symmetric oral movements during overt speech. Our atlases improve the currently available models of object recognition and speech production by adding neural dynamics via direct intra- and inter-hemispheric white matter tracts.

Exploring the Effects of EEG-Based Alpha Neurofeedback on Working Memory Capacity in Healthy Participants

Neurofeedback, an operant conditioning neuromodulation technique, uses information from brain activities in real-time via brain-computer interface (BCI) technology. This technique has been utilized to enhance the cognitive abilities, including working memory performance, of human beings. The aims of this study are to investigate how alpha neurofeedback can improve working memory performance in healthy participants and to explore the underlying neural mechanisms in a working memory task before and after neurofeedback. Thirty-six participants divided into the NFT group and the control group participated in this study. This study was not blinded, and both the participants and the researcher were aware of their group assignments. Increasing power in the alpha EEG band was used as a neurofeedback in the eyes-open condition only in the NFT group. The data were collected before and after neurofeedback while they were performing the N-back memory task (N = 1 and N = 2). Both groups showed improvement in their working memory performance. There was an enhancement in the power of their frontal alpha and beta activities with increased working memory load (i.e., 2-back). The experimental group showed improvements in their functional connections between different brain regions at the theta level. This effect was absent in the control group. Furthermore, brain hemispheric lateralization was found during the N-back task, and there were more intra-hemisphere connections than inter-hemisphere connections of the brain. These results suggest that healthy participants can benefit from neurofeedback and from having their brain networks changed after the training.

Connections between spatially distant primary language regions strengthen with age during infancy, as revealed by resting-state fNIRS

Objective. Hearing is an important sensory function that plays a key role in how children learn to speak and develop language skills. Although previous neuroimaging studies have established that much of brain network maturation happens in early childhood, our understanding of the developmental trajectory of language areas is still very limited. We hypothesized that typical development trajectory of language areas in early childhood could be established by analyzing the changes of functional connectivity in normal hearing infants at different ages using functional near-infrared spectroscopy. Approach. Resting-state data were recorded from two bilateral temporal and prefrontal regions associated with language processing by measuring the relative changes of oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) concentrations. Connectivity was calculated using magnitude-squared coherence of channel pairs located in (a) inter-hemispheric homologous and (b) intra-hemispheric brain regions to assess connectivity between homologous regions across hemispheres and two regions of interest in the same hemisphere, respectively. Main results. A linear regression model fitted to the age vs coherence of inter-hemispheric homologous test group revealed a significant coefficient of determination for both HbO (R 2 = 0.216, p = 0.0169) and HbR (R 2 = 0.206, p = 0.0198). A significant coefficient of determination was also found for intra-hemispheric test group for HbO (R 2 = 0.237, p = 0.0117) but not for HbR (R 2 = 0.111, p = 0.0956). Significance. The findings from HbO data suggest that both inter-hemispheric homologous and intra-hemispheric connectivity between primary language regions significantly strengthen with age in the first year of life. Mapping out the developmental trajectory of primary language areas of normal hearing infants as measured by functional connectivity could potentially allow us to better understand the altered connectivity and its effects on language delays in infants with hearing impairments.

Neurovascular coupling is preserved in chronic stroke recovery after targeted photothrombosis

Functional neuroimaging, which measures hemodynamic responses to brain activity, has great potential for monitoring recovery in stroke patients and guiding rehabilitation during recovery. However, hemodynamic responses after stroke are almost always altered relative to responses in healthy subjects and it is still unclear if these alterations reflect the underlying brain physiology or if the alterations are purely due to vascular injury. In other words, we do not know the effect of stroke on neurovascular coupling and are therefore limited in our ability to use functional neuroimaging to accurately interpret stroke pathophysiology. To address this challenge, we simultaneously captured neural activity, through fluorescence calcium imaging, and hemodynamics, through intrinsic optical signal imaging, during longitudinal stroke recovery. Our data suggest that neurovascular coupling was preserved in the chronic phase of recovery (2 weeks and 4 weeks post-stoke) and resembled pre-stroke neurovascular coupling. This indicates that functional neuroimaging faithfully represents the underlying neural activity in chronic stroke. Further, neurovascular coupling in the sub-acute phase of stroke recovery was predictive of long-term behavioral outcomes. Stroke also resulted in increases in global brain oscillations, which showed distinct patterns between neural activity and hemodynamics. Increased neural excitability in the contralesional hemisphere was associated with increased contralesional intrahemispheric connectivity. Additionally, sub-acute increases in hemodynamic oscillations were associated with improved sensorimotor outcomes. Collectively, these results support the use of hemodynamic measures of brain activity post-stroke for predicting functional and behavioral outcomes.

45 Using fetal ultrasound to predict developmental outcomes in children born with cardiac defects in Manitoba: A historical cohort study

Abstract Background The cavum septum pellucidum (CSP) is a normal anatomical cavity found in the mid-brain of the fetus and is routinely imaged at the time of mid-pregnancy obstetrical ultrasound as part of anatomic survey. Presence of the CSP reflects intact intrahemispheric connections and an intact corpus callosum. The CSP space then closes by the time of birth or early infancy, however persistence of the CSP into adulthood has been described in those with the schizophrenic phenotype of DiGeorge syndrome. Preliminary work by our group in Manitoba has shown utility in measurement of CSP width to improve non-invasive prenatal diagnosis of DiGeorge syndrome among fetuses with and without conotruncal cardiac defects. However, there exists no information about the relationship between fetal CSP width and future neurodevelopmental outcomes, such as Bayley-III scores, in children with cardiac lesions in the absence of underlying genetic comorbidities. Objectives To determine the relationship between cavum septum pellucidum (CSP) width and neurodevelopment in children born with sever cardiac defects. Design/Methods This was a historical cohort study of children born with cardiac anomalies in Manitoba (2009-2019). Eligible children with developmental pediatric follow-up between ages 18-24 months corrected age were identified using a clinical repository. Post-processing measurement of fetal CSP at mid-gestation using stored obstetrical ultrasounds was performed by two blinded and independent reviewers in a standardized fashion. Ultrasound reports were also reviewed to collate data about routine fetal biometry and imaging data then linked to demographics, birth information, surgical details and neurodevelopmental outcomes (Bayley-III scales). Linear regression models were used to evaluate the relationship between CSP width and Bayley-III scores; inferential statistics were used to compare outcomes between groups (biventricular versus single-ventricle repair). Results 78 of 111 eligible cases had stored ultrasound images and included in the analysis. Most children were delivered at term following vaginal delivery (71%), with normal birthweight and Apgars. Median CSP width was 3.8mm (SD 1.2). There was a range conotruncal cardiac anomalies and 47% required single-ventricle repair. There was no obvious relationship between CSP width and Bayley-III motor (p=0.932) or cognitive domains (p0.686), however there was a trend towards larger CSP and higher Bayley-III language scores (p=0.049). Conclusion The influence of the deoxygenated blood on the developing fetal brain in modifying outcomes for children with severe cardiac defects needs future study to improve postnatal development in this high-risk group.

Addressing spatial bias in intracranial EEG functional connectivity analyses for epilepsy surgical planning

Objective. To determine the effect of epilepsy on intracranial electroencephalography (EEG) functional connectivity, and the ability of functional connectivity to localize the seizure onset zone (SOZ), controlling for spatial biases. Approach. We analyzed intracranial EEG data from patients with drug-resistant epilepsy admitted for pre-surgical planning. We calculated intracranial EEG functional networks and determined whether changes in functional connectivity lateralized the SOZ using a spatial subsampling method to control for spatial bias. We developed a ‘spatial null model’ to localize the SOZ electrode using only spatial sampling information, ignoring EEG data. We compared the performance of this spatial null model against models incorporating EEG functional connectivity and interictal spike rates. Main results. About 110 patients were included in the study, although the number of patients differed across analyses. Controlling for spatial sampling, the average connectivity was lower in the SOZ region relative to the same anatomic region in the contralateral hemisphere. A model using intra-hemispheric connectivity accurately lateralized the SOZ (average accuracy 75.5%). A spatial null model incorporating spatial sampling information alone achieved moderate accuracy in classifying SOZ electrodes (mean AUC = 0.70, 95% CI 0.63–0.77). A model incorporating intracranial EEG functional connectivity and spike rate data further outperformed this spatial null model (AUC 0.78, p = 0.002 compared to spatial null model). However, a model incorporating functional connectivity without spike rate data did not significantly outperform the null model (AUC 0.72, p = 0.38). Significance. Intracranial EEG functional connectivity is reduced in the SOZ region, and interictal data predict SOZ electrode localization and laterality, however a predictive model incorporating functional connectivity without interictal spike rates did not significantly outperform a spatial null model. We propose constructing a spatial null model to provide an estimate of the pre-implant hypothesis of the SOZ, and to serve as a benchmark for further machine learning algorithms in order to avoid overestimating model performance because of electrode sampling alone.

Dual-site TMS as a tool to probe effective interactions within the motor network: a review.

Dual-site transcranial magnetic stimulation (ds-TMS) is well suited to investigate the causal effect of distant brain regions on the primary motor cortex, both at rest and during motor performance and learning. However, given the broad set of stimulation parameters, clarity about which parameters are most effective for identifying particular interactions is lacking. Here, evidence describing inter- and intra-hemispheric interactions during rest and in the context of motor tasks is reviewed. Our aims are threefold: (1) provide a detailed overview of ds-TMS literature regarding inter- and intra-hemispheric connectivity; (2) describe the applicability and contributions of these interactions to motor control, and; (3) discuss the practical implications and future directions. Of the 3659 studies screened, 109 were included and discussed. Overall, there is remarkable variability in the experimental context for assessing ds-TMS interactions, as well as in the use and reporting of stimulation parameters, hindering a quantitative comparison of results across studies. Further studies examining ds-TMS interactions in a systematic manner, and in which all critical parameters are carefully reported, are needed.

Aberrant beta-band brain connectivity predicts speech motor planning deficits in post-stroke aphasia

Impairments in speech production can have devastating effects on the overall quality of life in left-hemisphere stroke survivors with aphasia; however, there is a paucity of research focusing on neural deficits in speech motor planning networks that are activated prior to the onset of speech production in this clinical population. In the present study, we examined directional brain connectivity correlates of speech preparation and planning in low-β (13–20 Hz) and high-β (21–30 Hz) band neural oscillations in participants aphasia compared with controls prior to the onset of speech. Electroencephalographic (EEG) data were concurrently recorded from 33 participants with post-stroke aphasia and 22 neurologically intact controls while they engaged in speech production tasks. Using Granger causality, brain connectivity was calculated between electrode pairs that fell within fronto-frontal, fronto-central, and fronto-parietal networks implicated in sensorimotor integration and speech planning. Clinical assessment was further conducted in post-stroke participants to measure the severity of language impairment associated with aphasia. Increased intra-hemispheric connectivity was found within low- and high-β bands in the left parieto-central and parieto-frontal as well as the right fronto-frontal and fronto-central electrodes in post-stroke participants compared with controls prior to the onset of speech production. In addition, we found that decreased inter-hemispheric centro-central connectivity within high-β band was negatively correlated with aphasia severity whereas increased parieto-frontal connectivity within high-β band was positively correlated with aphasia severity. These findings suggest that participants with left-hemisphere stroke express aberrant brain connectivity within low- and high-β bands in both left and right hemispheres during the planning phase of speech production, and that these deficits are associated with specific aspects of their language impairment, as indicated by their clinical symptoms due to aphasia.