Virtual Lesion Research Articles

Common framework for “virtual lesion” and state-dependent TMS: The facilitatory/suppressive range model of online TMS effects on behavior

The behavioral effects of Transcranial Magnetic Stimulation (TMS) are often nonlinear; factors such as stimulation intensity and brain state can modulate the impact of TMS on observable behavior in qualitatively different manner. Here we propose a theoretical framework to account for these effects. In this model, there are distinct intensity ranges for facilitatory and suppressive effects of TMS – low intensities facilitate neural activity and behavior whereas high intensities induce suppression. The key feature of the model is that these ranges are shifted by changes in neural excitability: consequently, a TMS intensity, which normally induces suppression, can have a facilitatory effect if the stimulated neurons are being inhibited by ongoing task-related processes or preconditioning. For example, adaptation reduces excitability of adapted neurons; the outcome is that TMS intensities which inhibit non-adapted neurons induce a facilitation on adapted neural representations, leading to reversal of adaptation effects. In conventional “virtual lesion” paradigms, similar effects occur because neurons not involved in task-related processes are inhibited by the ongoing task. The resulting reduction in excitability can turn high intensity “inhibitory” TMS to low intensity “facilitatory” TMS for these neurons, and as task-related neuronal representations are in the inhibitory range, the outcome is a reduction in signal-to-noise ratio and behavioral impairment.

Phakopsora euvitis Causes Unusual Damage to Leaves and Modifies Carbohydrate Metabolism in Grapevine.

Asian grapevine rust (Phakopsora euvitis) is a serious disease, which causes severe leaf necrosis and early plant defoliation. These symptoms are unusual for a strict biotrophic pathogen. This work was performed to quantify the effects of P. euvitis on photosynthesis, carbohydrates, and biomass accumulation of grapevine. The reduction in photosynthetic efficiency of the green leaf tissue surrounding the lesions was quantified using the virtual lesion concept (β parameter). Gas exchange and responses of CO2 assimilation to increasing intercellular CO2 concentration were analyzed. Histopathological analyses and quantification of starch were also performed on diseased leaves. Biomass and carbohydrate accumulation were quantified in different organs of diseased and healthy plants. Rust reduced the photosynthetic rate, and β was estimated at 5.78, indicating a large virtual lesion. Mesophyll conductance, maximum rubisco carboxylation rate, and regeneration of ribulose-1,5-bisphosphate dependent on electron transport rate were reduced, causing diffusive and biochemical limitations to photosynthesis. Hypertrophy, chloroplast degeneration of mesophyll cells, and starch accumulation in cells close to lesions were observed. Root carbohydrate concentration was reduced, even at low rust severity. Asian grapevine rust dramatically reduced photosynthesis and altered the dynamics of production and accumulation of carbohydrates, unlike strict biotrophic pathogens. The reduction in carbohydrate reserves in roots would support polyetic damage on grapevine, caused by a polycyclic disease.

P 114 The occurence of semantic language errors induced by repetitive navigated transcranial magnetic stimulation based on different word characteristics

Objective Repetitive transcranial magnetic stimulation (rTMS) to map cortical language functions by inducing “virtual lesions” during task performance (e.g., picture-naming) has recently been introduced into pre-surgical diagnostics in brain tumor patients. We investigated to which extent the characteristics of the objects (words) used in the task influence the occurrence of semantically related language errors. Methods In a prospective single center study, we investigated thirteen right-handed, healthy volunteers (female n = 6/male n = 7) in 3 consecutive sessions by using 10 Hz, 30 Hz and 50 Hz-rTMS. After determination of the individual threshold reflecting motor cortex excitability, online-rTMS was applied during a picture-naming task: black-and-white drawings ( n = 50) of everyday objects were presented simultaneously with rTMS (triggered, delay = 0 ms) with rTMS. rTMS bursts lasted for 1.5 s (15 pulses). The rTMS was applied over the frontolateral, parietolateral and superior/middle temporal area of the left hemisphere. The language errors were rated by two independent examiners using post hoc video analysis. The frequency (number of errors per 100 rTMS pulses) of errors related to semantic processing (i.e., anomia and semantic paraphasia) was quantified. The speech arrest or a not identifiable word response were a measure of the error strength. All the objects allowing alternative naming responses (e.g., ball/ football) were excluded. The remaining words were grouped by the number of sillables in one- (1S; N = 19) and two-sillable words (2S; N = 25). For each object, the word frequency was assessed (by using google hits in german language) and correlated to the error rates by Pearson’s product moment correlation. Error rates were compared between 1S and 2S using McNemar’s test for paired count data. Results The number of sillables (1S vs. 2S) had no influence on the total error rate (1S: mean N = 73.9 errors/word vs. 2S: mean N = 79.9) or the error strength (1S: mean N = 19.5 vs. 2S: mean N = 19.5). By contrast, the rate of anomias (1S: mean N = 4.2 vs. 2S: mean N = 6.4) increased with the number of sillables ( p 0.01 ), regardless of the word frequency in German language (n.s.). For semantic paraphasias, a weak statistical tendency was observed ( p = 0.11), presumably due to few events (1S: mean N = 1.4 vs. 2S: mean N = 2.2). Regarding semantic paraphasias, the slightly higher rate of errors for 2-sillable words did not meet statistical significance ( p = 0.11), presumable due to the rareness of the events (mean N = 1.5 errors/word). Conclusion The complexity of the tested words, more specifically the number of sillables, seems to be significantly influencing the disruption of semantic word expression induced by rTMS. Therefore, using longer words for language mapping might be favourable in order to increase the true-positive rate of mapping results.

Computational neuroanatomy of human stratum proprium of interparietal sulcus

Recent advances in diffusion-weighted MRI (dMRI) and tractography have enabled identification of major long-range white matter tracts in the human brain. Yet, our understanding of shorter tracts, such as those within the parietal lobe, remains limited. Over a century ago, a tract connecting the superior and inferior parts of the parietal cortex was identified in a post-mortem study: stratum proprium of interparietal sulcus (SIPS; Sachs, Das hemisphärenmark des menschlichen grosshirns. Verlag von georg thieme, Leipzig, 1892). The tract has since been replicated in another fibre dissection study (Vergani et al., Cortex 56:145–156, 2014), however, it has not been fully investigated in the living human brain and its precise anatomical properties are yet to be described. We used dMRI and tractography to identify and characterise SIPS in vivo, and explored its spatial proximity to the cortical areas associated with optic-flow processing using fMRI. SIPS was identified bilaterally in all subjects, and its anatomical position and trajectory are consistent with previous post-mortem studies. Subsequent evaluation of the tractography results using the linear fascicle evaluation and virtual lesion analysis yielded strong statistical evidence for SIPS. We also found that the SIPS endpoints are adjacent to the optic-flow selective areas. In sum, we show that SIPS is a short-range tract connecting the superior and inferior parts of the parietal cortex, wrapping around the intraparietal sulcus, and that it may be a crucial anatomy underlying optic-flow processing. In vivo identification and characterisation of SIPS will facilitate further research on SIPS in relation to cortical functions, their development, and diseases that affect them.

A Data-Driven Approach to Responder Subgroup Identification after Paired Continuous Theta Burst Stimulation.

Background: Modulation of cortical excitability by transcranial magnetic stimulation (TMS) is used for investigating human brain functions. A common observation is the high variability of long-term depression (LTD)-like changes in human (motor) cortex excitability. This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS) as a basis for subject selection.Methods: The effects of paired cTBS using 80% active motor threshold (AMT) in 31 healthy volunteers were assessed at the primary motor cortex (M1) corresponding to the representation of the first dorsal interosseous (FDI) muscle of the left hand, before and up to 50 min after plasticity induction. The changes in motor evoked potentials (MEPs) were analyzed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM) and computed ABC analysis.Results: The probability density distribution of the MEP changes from baseline was tri-modal, showing a clear separation at 80.9%. Subjects displaying at least this degree of LTD-like changes were n = 6 responders. By contrast, n = 7 subjects displayed a paradox response with increase in MEP. Reassessment using ABC analysis as alternative approach led to the same n = 6 subjects as a distinct category.Conclusion: Depressive effects of paired cTBS using 80% AMT endure at least 50 min, however, only in a small subgroup of healthy subjects. Hence, plasticity induction by paired cTBS might not reflect a general mechanism in human motor cortex excitability. A mathematically supported criterion is proposed to select responders for enrolment in assessments of human brain functional networks using virtual brain lesions.

Abstract 4536: Using diffusion weighted imaging (DWI) data to accurately predict electric field delivery to the tumor during TTFields treatment

Abstract Tumor Treating Fields (TTFields) are low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency range, delivered through two pairs of transducer arrays placed on the patient's scalp. TTFields are an anti-mitotic modality approved for the treatment of glioblastoma multiforme (GBM). Simulation-based studies show that TTFields distribution within the brain depends on the location of the arrays on the scalp as well as the anatomy of the patient. Therefore, to study how field distribution influences disease progression requires the creation of patient-specific computational models. To date the creation of such models is based on accurate segmentation of MRI images into various tissues, and further of volume mesh assembly. These tasks are performed using semi-automatic, labor-intensive algorithms, making this approach impractical for studies which require the creation of a large number of patient models. We recently outlined that diffusion tensor imaging (DTI) could be used to construct realistic head models for simulating TTFields distribution without the need for complex segmentation of the brain. This is possible because the diffusion tensors evaluated from DTI can be scaled into anisotropic conductivity tensors using simple relationships. However, the approach is limited because the acquisition of high-quality DTI data is not widely practiced for GBM patients. Yet, shorter diffusion weighted imaging (DWI) sequences, such as an apparent diffusion coefficient (ADC) map or trace image, are common diagnostic techniques. The aim of this study was to test whether DWI data could potentially be used to create realistic head models. We used a previously developed head model created from structural and DTI data of a healthy individual. To test pathological scenarios, virtual lesions were placed. To simulate data acquired with DWI, we substituted the diffusion tensor at each point within the model with the mean diffusion (MD), which is the value that can be measured using DWI. The computational model was then completed by scaling the MD into a voxel-wise isotropic conductivity map using the same relationship as applied to convert anisotropic diffusion into conductivity tensors. TTFields distributions within the model were then evaluated for various array layouts and tumor locations. The field distribution within the DWI-derived models did not vary significantly from those found in the DTI-derived models. The highest deviation between models was a difference of 5% in the average electric field intensity in the tumor. The study shows that DWI data can be used to develop realistic head models for simulating TTFields, opening a new avenue for creating patient-specific computational models on a large scale. These models could be beneficial for retrospective studies investigating possible connections between field distribution and disease outcome. Citation Format: Cornelia Wenger, Ze'ev Bomzon, Pedro Cavaleiro Miranda. Using diffusion weighted imaging (DWI) data to accurately predict electric field delivery to the tumor during TTFields treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4536. doi:10.1158/1538-7445.AM2017-4536

Involvement of the Left Supramarginal Gyrus in Manipulation Judgment Tasks: Contributions to Theories of Tool Use.

Two theories of tool use, namely the gesture engram and the technical reasoning theories, make distinct predictions about the involvement of the left inferior parietal lobe (IPL) in manipulation judgement tasks. The objective here is to test these alternative predictions based on previous studies on manipulation judgment tasks using transcranial magnetic stimulations (TMS) targeting the left supramarginal gyrus (SMG). We review recent TMS studies on manipulation judgement tasks and confront these data with predictions made by both tool use theories. The left SMG is a highly intertwined region, organized following several functionally distinct areas and TMS may have disrupted a cortical network involved in the ability to use tools rather than only one functional area supporting manipulation knowledge. Moreover, manipulation judgement tasks may be impaired following virtual lesions outside the IPL. These data are more in line with the technical reasoning hypothesis, which assumes that the left IPL does not store manipulation knowledge per se. (JINS, 2017, 23, 685-691).

Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex.

A growing body of evidence have suggested that non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right-handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS-inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS-inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal patients.

Relationship Between Perisylvian Essential Language Sites and Arcuate Fasciculus in the Left Hemisphere of Healthy Adults.

Essential language sites and the arcuate fasciculus (AF) have been extensively researched. However, the relationship between them remains insufficiently studied, especially in healthy people. Navigated transcranial magnetic stimulation (nTMS) is increasingly used in language mapping. While enjoying the advantage of non-invasiveness, it is also capable of inducing a virtual lesion in the brain. Thus, it offers the possibility of using the virtual-lesion method to study the healthy brain. This study combined nTMS and diffusion tensor imaging (DTI) tractography to investigate the relationship between essential language sites and the AF in 30 healthy right-handed volunteers. A total of 143 essential language sites were identified using nTMS, and a total of 175 AF terminations were identified using DTI tractography. Sixty-six sites had a direct correlation with the AF, accounting for 46% of the total essential language sites. Forty-seven AF terminations harbored essential language sites, accounting for 27% of the total AF terminations. Upon data rendering to the cortical parcellation system, a region-related heterogeneity of the correlation rate was found. This study provides the first data on the relationship between essential language sites and the AF in healthy adults.

P260 Modulating motor learning using cathodal tDCS

Following a stroke, anatomically distinct regions of the motor network including both ipsi- and contralesional areas have been demonstrated to increase when moving the stroke-affected arm. However, it is not clear what this increase in activity represents. Increased activity has been shown to be related to residual hand function in chronic stroke patients, however those patients with the highest levels of activity in these regions also show the worst recovery. Transcranial direct current stimulation (tDCS) is being increasingly investigated for its potential as an adjunct therapeutic tool for rehabilitation due to its ability to modulate underlying cortical excitability and induce the neurochemical changes thought to contribute to plasticity. For optimisation of this tool, a complete understanding of the wider motor network and the regions that could provide compensatory activity is needed. Studies in chronic stroke patients are inherently limited due to the inhomogeneity of lesion volume and location. An alternative is investigated here: the modelling of a stroke-type lesion in healthy participants using cathodal tDCS to temporarily down-regulate activity in a target area of the cortex. Combining cathodal tDCS with a model of motor recovery (a simple motor learning task) during BOLD functional MRI, we hoped to identify candidate regions that might demonstrate compensatory activity. Cathodal tDCS applied to left motor cortex (M1) during an explicit sequence-learning task performed with the right hand, resulted in down-regulation of activity within left M1, with a concurrent, possibly compensatory, increase in activity in the right M1. By contrast, delivery of tDCS prior to the task led to greater learning-related activity changes in left M1, Supplementary Motor Area (SMA) and dorsal premotor cortex (PMd) compared to concurrent and sham stimulation. These results, combined with no significant difference in behavioural performance across the stimulation groups identify that cathodal tDCS induced “virtual lesions” could be a suitable model for stroke lesions and that both ipsi- and contralateral regions could be considered as therapeutic targets for compensatory up-regulation using tDCS in stroke recovery.

P269 Utility of TMS in presurgical mapping of eloquent cortices in children

Introduction The unique ability of TMS to non-invasively induce evoked responses and virtual lesions combined with improved accuracy afforded by image guidance has spurred its clinical applications. While the utility of presurgical motor and language mapping using TMS has been demonstrated in adults ( Picht, 2013 , Tarapore, 2012 ), its use in pediatric patients is in its infancy ( Narayana, 2015 ). We report here, successful functional mapping of both motor and language cortices using TMS in children. Methods Thirty-nine children (23 M, age range 0.6–18 years) undergoing surgery for brain tumors or refractory epilepsy underwent motor and language mapping using a navigated TMS system (Nexstim 4.3) (see Table 1 for the location of the lesions and type of mapping). The motor mapping (n = 22) included determination of localization and extent of primary motor cortex for hand and mouth. Language areas were localized as patients (n = 26) performed an object-naming paradigm implemented in the Nexspeech module (Nexstim Inc.) using 5 Hz TMS. TMS was applied to lateral temporal and frontal regions in both hemispheres and the observed errors were categorized using previously established criteria ( Picht, 2013 ). Results All patients tolerated TMS and did not experience any serious adverse effects. Motor cortex was successfully mapped in all but one patient. The TMS motor maps aided in determining the surgical approach and extent of resection in all patients (see Fig. 1-top). Language area localization and hemispheric dominance were successfully determined in 22 of the 26 patients. TMS derived language maps were used in conjunction with MEG, fMRI, WADA and cortical stimulation mapping in determining the surgical approach and extent of resection in these patients (see Fig. 1-bottom) ( Babajani-Feremi, 2016 ). Conclusions TMS is a safe and noninvasive means of localizing motor and language functions and recent improvements in accuracy and ease of application of TMS are especially beneficial in pediatric neurosurgery and neurology. We believe that the critical information that TMS provides, coupled with its ease of use, will result in increasing pediatric applications in the near future. Download : Download high-res image (264KB) Download : Download full-size image Download : Download high-res image (637KB) Download : Download full-size image

Effect of Radiation Dose Reduction and Reconstruction Algorithm on Image Noise, Contrast, Resolution, and Detectability of Subtle Hypoattenuating Liver Lesions at Multidetector CT: Filtered Back Projection versus a Commercial Model-based Iterative Reconstruction Algorithm.

Purpose To determine the effect of radiation dose and iterative reconstruction (IR) on noise, contrast, resolution, and observer-based detectability of subtle hypoattenuating liver lesions and to estimate the dose reduction potential of the IR algorithm in question. Materials and Methods This prospective, single-center, HIPAA-compliant study was approved by the institutional review board. A dual-source computed tomography (CT) system was used to reconstruct CT projection data from 21 patients into six radiation dose levels (12.5%, 25%, 37.5%, 50%, 75%, and 100%) on the basis of two CT acquisitions. A series of virtual liver lesions (five per patient, 105 total, lesion-to-liver prereconstruction contrast of -15 HU, 12-mm diameter) were inserted into the raw CT projection data and images were reconstructed with filtered back projection (FBP) (B31f kernel) and sinogram-affirmed IR (SAFIRE) (I31f-5 kernel). Image noise (pixel standard deviation), lesion contrast (after reconstruction), lesion boundary sharpness (average normalized gradient at lesion boundary), and contrast-to-noise ratio (CNR) were compared. Next, a two-alternative forced choice perception experiment was performed (16 readers [six radiologists, 10 medical physicists]). A linear mixed-effects statistical model was used to compare detection accuracy between FBP and SAFIRE and to estimate the radiation dose reduction potential of SAFIRE. Results Compared with FBP, SAFIRE reduced noise by a mean of 53% ± 5, lesion contrast by 12% ± 4, and lesion sharpness by 13% ± 10 but increased CNR by 89% ± 19. Detection accuracy was 2% higher on average with SAFIRE than with FBP (P = .03), which translated into an estimated radiation dose reduction potential (±95% confidence interval) of 16% ± 13. Conclusion SAFIRE increases detectability at a given radiation dose (approximately 2% increase in detection accuracy) and allows for imaging at reduced radiation dose (16% ± 13), while maintaining low-contrast detectability of subtle hypoattenuating focal liver lesions. This estimated dose reduction is somewhat smaller than that suggested by past studies. © RSNA, 2017 Online supplemental material is available for this article.

Medical Data Point Clouds Reconstruction Algorithm Based on Tensor Product B-Spline Approximation in Virtual Surgery

A complete 3D visualization method for virtual liver lesion model was proposed by taking patients’ abdomen CT slices as data source. Firstly, Gradient Vector Flow-Snake algorithm that combines with region force was adopted to fast and accurately extract the contour points in patients’ CT slices. Then 3D cloud data of these contour points was simplified uniformly, and a distance-field-based method of distribution field fitting for B-spline surface was presented to fast establish the lesion model roughly. Then, an interactive node fine tuning method Interactive Marching Nodes was proposed, so the model can be optimized according to requirements of users. Finally, realistic lesion model was generated through texture mapping. Experiments suggest that this approach is suitable for various kinds of lesions with the whole process taking only a few minutes, and the generated model has high precision, which is of some significance in the study of virtual surgeries.

The potential application of transcranial magnetic stimulation in ophthalmology: a brief perspective

Transcranial magnetic stimulation (TMS), while employed in both cognitive investigations and evaluated as a potential therapeutic technique for several conditions, is not widely used in ophthalmology. As a technique, one of the advantages of TMS is that it can create a “virtual lesion”, or temporary disruption of the functioning of a brain area, to facilitate investigation of the processes that the disrupted area may be involved in. In ophthalmology, higher association cortex is associated with visual cognition and control of eye movements, processes which could further be investigated using TMS experiments. This paper aims to provide a perspective of how TMS could be more broadly applied in ophthalmology.

Waterjet submucosal dissection of porcine esophagus with the HybridKnife and ERBEJET 2 system: a pilot study.

Background and study aims Esophageal endoscopic submucosal dissection (ESD) is technically difficult because of narrow working spaces and ease of perforation due to the lack of serosa. HybridKnife is a recently developed ESD device that is combined with the high pressure waterjet ERBEJET 2 system to lift mucosa. We hypothesized that this waterjet could make submucosal dissection safer and studied this in porcine esophagus. Materials and methods Water pressures of 30 – 70 bar were tested to determine the appropriate pressure for waterjet ESD with HybridKnife (WJ-ESD) in one pig. WJ-ESD safety and completion were compared with those of conventional ESD using DualKnife (C-ESD) as a reference. Each of three virtual esophageal lesions in two pigs were resected alternatively using both methods from the lower to upper esophagus. For WJ-ESD, the submucosa, apart from hard fibrous tissues, was dissected using water pressure alone. Results Using 50 bar of water pressure resulted in the best balance between proper dissection and view-disturbing water backflow. The dissection speeds for the lower, middle, and upper esophagus were 0.2, 0.9, and 0.2 cm2/min in 50 bar WJ-ESD and 1.1, 0.5, and 1.0 cm2/min in C-ESD, respectively. Minor bleeding was frequent in WJ-ESD, but was easily stopped by electrocoagulation with the same needle. No perforation was observed in either procedure. Thermal damage to dissected tissues appeared mild, and the extent of muscle injury was lower for WJ-ESD (4, 6, and 8 %) compared with C-ESD (14, 16, and 7 %). Conclusions WJ-ESD could be completed safely for porcine esophagus with less damage to the muscle layer compared with C-ESD.

Periventricular White Matter Is a Nexus for Network Connectivity in the Human Brain.

The edges of the structural connectome traverse the white matter to connect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Characterization of the geometry of the structural connectome could provide an improved understanding of the relative importance of various white matter regions to the network architecture of the human brain in normal development and aging, as well as in white matter diseases with regionally specific patterns of vulnerability. Edge density imaging (EDI) has previously been used to show that the posterior periventricular white matter contains a disproportionately large number of connectome edges. In this study, the regional distribution of connectome edges within cerebral white matter, including the importance of posterior periventricular white matter, is further investigated and demonstrated to be invariant to different gray matter parcellations and different diffusion MRI acquisition and postprocessing/tractography methods. An examination of the highest k-core edges and a virtual lesion analysis illuminate hemispheric asymmetries (left>right) in the embedding of connectome edges. Therefore, EDI reveals specific areas of vulnerability within the white matter connectivity of the human brain, especially in the periventricular white matter. The idea of a periventricular nexus fits with the known neurobiology of brain development and may result from simple geometrical considerations in minimizing wiring cost in structural brain connectivity.

Transcranial Magnetic Stimulation on Rodent Models.

Transcranial magnetic stimulation (TMS) is a non-invasive method that can be used as an interventional technique to investigate causality in the brain-behavior relationship, through depolarization or hyperpolarization in the neurons of the brain. Different techniques of TMS can be used to investigate causality in the brain-behavior relationship. The behavioral effects induced by TMS are complex since it has been shown that the performance in the same cognitive task can be either facilitated or inhibited depending on the area being stimulated. To date, most studies involving TMS are focused mainly on the facilitation properties of this technique. It is used to treat a wide-range of neurological and psychiatric conditions such as depression, ischemia, Alzheimer's disease, or motor impairment. Interestingly, TMS can be used to induce a virtual lesion that could provide a valuable and much needed model of cognitive impairments in early preclinical development. This review describes the existing TMS paradigms in rodents and the major challenges that were encountered by the researchers as the method was translated from clinical to preclinical applications. In summary, the existing knowledge gained in animal research emphasizes the necessity to investigate new TMS paradigms in the preclinical setting and its effects.

Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

TH‐CD‐207B‐04: Is TTF a True Representation of the Sharpness Property of a Non‐Linear CT System?

Purpose:To investigate if the task‐transfer‐function (TTF) accurately models the transfer properties of a CT system for lung nodule imaging.Methods:An anthropomorphic lung phantom was imaged using a standard chest protocol on a clinical CT scanner with and without 24 physically inserted synthetic lesions (nominal diameter: 8 – 10 mm). Images were reconstructed using FBP and iterative algorithm (SAFIRE, Siemens Healthcare). 3D TTF was measured using an established technique. Corresponding idealized virtual lesions were blurred with the TTF and superimposed onto lesion‐less phantom images. Images of the physically and virtually inserted lesions were compared in terms of rendition of spatial features (blurriness of the edges), lesion morphology, and lesion volume. Feature rendition was measured in terms root‐mean‐square (RMS) of the frequency power of the native and TTF‐transferred lesion edge transition. Morphology was assessed with the Regional Hausdorff Distance (RHD) using custom written code (MATLAB v2015b). Volumes were measured using a clinical segmentation tool (iNtution, TeraRecon).Results:The RMS was less than 0.02 and 0.05 for FBP and IR respectively. Using the nonlinear mixed effect (nlme) package (R, www.r‐project.org), the difference in RHD between virtual and physical lesions was 5% on average. There was less than 1 ± 5% (R2 > 0.97) and 3 ± 4% (R2 > 0.97) difference between the volumes of the physical lesions and the corresponding virtual lesions for FBP and IR respectively. Additionally, was closer concordance for images reconstructed with FBP than iterative reconstruction.Conclusion:The TTF was found to accurately model the transfer properties of the CT imaging system on lung lesions for both FBP and iterative reconstruction algorithms. TTF was found to offer slightly better lesion renditions when modeling images reconstructed with FBP versus iterative reconstruction. This methodology will be used in future investigation of more complex imaging tasks such as low contrast detectability of known lesions.

Robustness and dynamicity of functional networks in phantom sound

Phantom sound perception is the perception of a sound in the absence of a corresponding external sound source. It is a common symptom for which no treatment exists. Gaining a better understanding of its pathophysiology by applying network science might help in identifying targets in the brain for neuromodulatory approaches to treat this elusive symptom. Brain networks are commonly organized as functional modules which have a densely connected core network coupled to a communally-organized peripheral network. The core network is called the rich club network and the peripheral network is divided into the feeder and local networks. In current study, we investigate the effects of virtual lesions on the endogenous dynamics, complexity and robustness of the remaining brain. It is hypothesized that depending on whether nodes is functionally central to the network or not, the robustness and dynamics of the network change when a lesion in introduced. We therefore investigate the effect of introducing a virtual focal lesion randomly to different nodes is in the tinnitus network and contrast it to the effect of specifically targeting the nodes of the rich-club, feeder and local nodes in patients experiencing a phantom sound (i.e. tinnitus). The tinnitus and control networks were computed from the source-localized EEG of 311 tinnitus patients and 256 control subjects. The results of the current study indicate that both the tinnitus and control networks are robust to the attack on random and rich club nodes, but are drastically modified when attacked from the periphery, especially while targeting the feeder hubs. In both the tinnitus and control networks, feeder nodes were found to have a higher betweenness centrality value than the rich club nodes. This shows that the feeders have a larger influence on the information transmission through the brain than the rich club nodes, by transferring information from the peripheral communities to the core. Further, evidence for the theoretical model of a multimodal tinnitus network is also presented showing that the tinnitus network is divided into individual, separable modules each possibly encoding a different aspect of tinnitus. The current study alludes to the concept that the efficient modification of the tinnitus network is theoretically possible by disconnecting the individual communities from the core of the pathological network.