Lesion network mapping for symptom localization: recent developments and future directions.

PURPOSE OF REVIEW: Focal lesions causing specific neurological or psychiatric symptoms can occur in multiple different brain locations, complicating symptom localization. Here, we review lesion network mapping, a technique used to aid localization by mapping lesion-induced symptoms to brain circuits rather than individual brain regions. We highlight recent examples of how this technique is being used to investigate clinical entities and identify therapeutic targets. RECENT FINDINGS: To date, lesion network mapping has successfully been applied to more than 40 different symptoms or symptom complexes. In each case, lesion locations were combined with an atlas of human brain connections (the human connectome) to map heterogeneous lesion locations causing the same symptom to a common brain circuit. This approach has lent insight into symptoms that have been difficult to localize using other techniques, such as hallucinations, tics, blindsight, and pathological laughter and crying. Further, lesion network mapping has recently been applied to lesions that improve symptoms, such as tremor and addiction, which may translate into new therapeutic targets. SUMMARY: Lesion network mapping can be used to map lesion-induced symptoms to brain circuits rather than single brain regions. Recent findings have provided insight into long-standing clinical mysteries and identified testable treatment targets for circuit-based and symptom-based neuromodulation.

Investigation of Asleep versus Awake Motor Mapping in Resective Brain Surgery.

OBJECTIVE: To develop an asleep motor mapping paradigm for accurate detection of the corticospinal tract during glioma surgery and compare outcomes with awake patients undergoing glioma resection. METHODS: A consecutive cohort of adult patients undergoing craniotomy for suspected diffuse glioma with tumor in a perirolandic location who had awake or asleep cortical and subcortical motor mapping with positive areas of motor stimulation were assessed for postoperative extent of resection (EOR), permanent neurological deficit, and proximity of stimulation to diffusion tensor imaging-based corticospinal tract depiction on preoperative magnetic resonance imaging. Outcome data were compared between asleep and awake groups. RESULTS: In the asleep group, all 16 patients had improved or no change in motor function at last follow-up (minimum 3 months of follow-up). In the awake group, all 23 patients had improved function or no change at last follow-up. EOR was greater in the asleep group (mean [SD] EOR 88.71% [17.56%]) versus the awake group (mean [SD] EOR 80.62% [24.44%]), although this difference was not statistically significant (P = 0.3802). Linear regression comparing distance from stimulation to corticospinal tract in asleep (n = 14) and awake (n = 4) patients was r = -0.3759, R2 = 0.1413, P = 0.1853, and 95% confidence interval = -0.4453 to 0.09611 and r = 0.7326, R2 = 0.5367, P = 0.2674, and 95% confidence interval = -7.042 to 14.75, respectively. CONCLUSION: In this small patient series, asleep motor mapping using commonly available motor evoked potential hardware appears to be safe and efficacious in regard to EOR and functional outcomes.

Use of Stereoelectroencephalography Beyond Epilepsy: A Systematic Review.

BACKGROUND: Stereoelectroencephalography (sEEG) is an increasingly popular surgical technique used clinically to study neural circuits involved in medication-refractory epilepsy, and it is concomitantly used in the scientific investigation of neural circuitry underlying behavior. METHODS: Using PRISMA guidelines, the U.S. National Library of Medicine at the National Institutes of Health PubMed database was queried for investigational or therapeutic applications of sEEG in human subjects. Abstracts were analyzed independently by 2 authors for inclusion or exclusion. RESULTS: The study search identified 752 articles, and after exclusion criteria were applied, 8 studies were selected for in-depth review. Among those 8 studies, 122 patients were included, with indications ranging from schizophrenia to Parkinson disease. All the included studies were single-institution case series representing level IV scientific evidence. CONCLUSIONS: sEEG is an important method in epilepsy surgery that could be applied to other neurologic and psychiatric diseases. Information from these studies could provide additional pathophysiologic information and lead to further development and refinement of neuromodulation therapies for such conditions.

Accelerating quantitative susceptibility and R2* mapping using incoherent undersampling and deep neural network reconstruction.

Quantitative susceptibility mapping (QSM) and R2* mapping are MRI post-processing methods that quantify tissue magnetic susceptibility and transverse relaxation rate distributions. However, QSM and R2* acquisitions are relatively slow, even with parallel imaging. Incoherent undersampling and compressed sensing reconstruction techniques have been used to accelerate traditional magnitude-based MRI acquisitions; however, most do not recover the full phase signal, as required by QSM, due to its non-convex nature. In this study, a learning-based Deep Complex Residual Network (DCRNet) is proposed to recover both the magnitude and phase images from incoherently undersampled data, enabling high acceleration of QSM and R2* acquisition. Magnitude, phase, R2*, and QSM results from DCRNet were compared with two iterative and one deep learning methods on retrospectively undersampled acquisitions from six healthy volunteers, one intracranial hemorrhage and one multiple sclerosis patients, as well as one prospectively undersampled healthy subject using a 7T scanner. Peak signal to noise ratio (PSNR), structural similarity (SSIM), root-mean-squared error (RMSE), and region-of-interest susceptibility and R2* measurements are reported for numerical comparisons. The proposed DCRNet method substantially reduced artifacts and blurring compared to the other methods and resulted in the highest PSNR, SSIM, and RMSE on the magnitude, R2*, local field, and susceptibility maps. Compared to two iterative and one deep learning methods, the DCRNet method demonstrated a 3.2% to 9.1% accuracy improvement in deep grey matter susceptibility when accelerated by a factor of four. The DCRNet also dramatically shortened the reconstruction time of single 2D brain images from 36-140 seconds using conventional approaches to only 15-70 milliseconds.

Perinatal stroke: mapping and modulating developmental plasticity.

Most cases of hemiparetic cerebral palsy are caused by perinatal stroke, resulting in lifelong disability for millions of people. However, our understanding of how the motor system develops following such early unilateral brain injury is increasing. Tools such as neuroimaging and brain stimulation are generating informed maps of the unique motor networks that emerge following perinatal stroke. As a focal injury of defined timing in an otherwise healthy brain, perinatal stroke represents an ideal human model of developmental plasticity. Here, we provide an introduction to perinatal stroke epidemiology and outcomes, before reviewing models of developmental plasticity after perinatal stroke. We then examine existing therapeutic approaches, including constraint, bimanual and other occupational therapies, and their potential synergy with non-invasive neurostimulation. We end by discussing the promise of exciting new therapies, including novel neurostimulation, brain-computer interfaces and robotics, all focused on improving outcomes after perinatal stroke.

High-Density EEG in Current Clinical Practice and Opportunities for the Future.

SUMMARY: High-density EEG (HD-EEG) recordings use a higher spatial sampling of scalp electrodes than a standard 10-20 low-density EEG montage. Although several studies have demonstrated improved localization of the epileptogenic cortex using HD-EEG, widespread implementation is impeded by cost, setup and interpretation time, and lack of specific or sufficient procedural billing codes. Despite these barriers, HD-EEG has been in use at several institutions for years. These centers have noted utility in a variety of clinical scenarios where increased spatial resolution from HD-EEG has been required, justifying the extra time and cost. We share select scenarios from several centers, using different recording techniques and software, where HD-EEG provided information above and beyond the standard low-density EEG. We include seven cases where HD-EEG contributed directly to current clinical care of epilepsy patients and highlight two novel techniques which suggest potential opportunities to improve future clinical care. Cases illustrate how HD-EEG allows clinicians to: case 1-lateralize falsely generalized interictal epileptiform discharges; case 2-improve localization of falsely generalized epileptic spasms; cases 3 and 4-improve localization of interictal epileptiform discharges in anatomic regions below the circumferential limit of standard low-density EEG coverage; case 5-improve noninvasive localization of the seizure onset zone in lesional epilepsy; cases 6 and 7-improve localization of the seizure onset zone to guide invasive investigation near eloquent cortex; case 8-identify epileptic fast oscillations; and case 9-map language cortex. Together, these nine cases illustrate that using both visual analysis and advanced techniques, HD-EEG can play an important role in clinical management.

Hearing loss impacts gray and white matter across the lifespan: Systematic review, meta-analysis and meta-regression.

Hearing loss is a heterogeneous disorder thought to affect brain reorganization across the lifespan. Here, structural alterations of the brain due to hearing loss are assessed by using unique effect size metrics based on Cohen's d and Hedges' g. These metrics are used to map coordinates of gray matter (GM) and white matter (WM) alterations from bilateral congenital and acquired hearing loss populations. A systematic review and meta-analysis revealed m = 72 studies with structural alterations measured with magnetic resonance imaging (MRI) (bilateral = 64, unilateral = 8). The bilateral studies categorized hearing loss into congenital and acquired cases (n = 7,445) and control cases (n = 2,924), containing 66,545 datapoint metrics. Hearing loss was found to affect GM and underlying WM in nearly every region of the brain. In congenital hearing loss, GM decreased most in the frontal lobe. Similarly, acquired hearing loss had a decrease in frontal lobe GM, albeit the insula was most decreased. In congenital, WM underlying the frontal lobe GM was most decreased. In congenital, the right hemisphere was more negatively impacted than the left hemisphere; however, in acquired, this was the opposite. The WM alterations most frequently underlined GM alterations in congenital hearing loss, while acquired hearing loss studies did not frequently assess the WM metric. Future studies should use the endophenotype of hearing loss as a prognostic template for discerning clinical outcomes.

Lesion-based structural and functional networks in patients with step length asymmetry after stroke.

OBJECTIVE: The aim of this study was to determine common structural and functional networks associated with asymmetric step length after unilateral ischemic stroke. METHODS: Thirty-nine chronic stroke patients were divided into two groups, based on the presence or absence of asymmetric step length. In each group, each lesion was mapped onto a brain magnetic resonance image. The structural and functional networks of brain regions connected to each lesion were identified using a public diffusion tensor and resting state function magnetic resonance image dataset. To identify brain regions associated with asymmetric step length, we conducted voxel-wise independent sample t-tests for structural and function lesion network maps. RESULTS: At least 85% of lesions showed functional network overlap in the bilateral frontal lobe. Functional connectivity of the dorsolateral prefrontal cortex in the contralesional hemisphere was significantly decreased in group 1 compared to that in group 2. CONCLUSIONS: The dorsolateral prefrontal cortex may have an important role in compensating for an asymmetric step length after a unilateral stroke.

Embracing diversity and inclusivity in an academic setting: Insights from the Organization for Human Brain Mapping.

Scientific research aims to bring forward innovative ideas and constantly challenges existing knowledge structures and stereotypes. However, women, ethnic and cultural minorities, as well as individuals with disabilities, are systematically discriminated against or even excluded from promotions, publications, and general visibility. A more diverse workforce is more productive, and thus discrimination has a negative impact on science and the wider society, as well as on the education, careers, and well-being of individuals who are discriminated against. Moreover, the lack of diversity at scientific gatherings can lead to micro-aggressions or harassment, making such meetings unpleasant, or even unsafe environments for early career and underrepresented scientists. At the Organization for Human Brain Mapping (OHBM), we recognized the need for promoting underrepresented scientists and creating diverse role models in the field of neuroimaging. To foster this, the OHBM has created a Diversity and Inclusivity Committee (DIC). In this article, we review the composition and activities of the DIC that have promoted diversity within OHBM, in order to inspire other organizations to implement similar initiatives. Activities of the committee over the past four years have included (a) creating a code of conduct, (b) providing diversity and inclusivity education for OHBM members, (c) organizing interviews and symposia on diversity issues, and (d) organizing family-friendly activities and providing childcare grants during the OHBM annual meetings. We strongly believe that these activities have brought positive change within the wider OHBM community, improving inclusivity and fostering diversity while promoting rigorous, ground-breaking science. These positive changes could not have been so rapidly implemented without the enthusiastic support from the leadership, including OHBM Council and Program Committee, and the OHBM Special Interest Groups (SIGs), namely the Open Science, Student and Postdoc, and Brain-Art SIGs. Nevertheless, there remains ample room for improvement, in all areas, and even more so in the area of targeted attempts to increase inclusivity for women, individuals with disabilities, members of the LGBTQ+ community, racial/ethnic minorities, and individuals of lower socioeconomic status or from low and middle-income countries. Here, we present an overview of the DIC's composition, its activities, future directions and challenges. Our goal is to share our experiences with a wider audience to provide information to other organizations and institutions wishing to implement similar comprehensive diversity initiatives. We propose that scientific organizations can push the boundaries of scientific progress only by moving beyond existing power structures and by integrating principles of equity and inclusivity in their core values.

Virtual brain grafting: Enabling whole brain parcellation in the presence of large lesions.

Brain atlases and templates are at the heart of neuroimaging analyses, for which they facilitate multimodal registration, enable group comparisons and provide anatomical reference. However, as atlas-based approaches rely on correspondence mapping between images they perform poorly in the presence of structural pathology. Whilst several strategies exist to overcome this problem, their performance is often dependent on the type, size and homogeneity of any lesions present. We therefore propose a new solution, referred to as Virtual Brain Grafting (VBG), which is a fully-automated, open-source workflow to reliably parcellate magnetic resonance imaging (MRI) datasets in the presence of a broad spectrum of focal brain pathologies, including large, bilateral, intra- and extra-axial, heterogeneous lesions with and without mass effect. The core of the VBG approach is the generation of a lesion-free T1-weighted image, which enables further image processing operations that would otherwise fail. Here we validated our solution based on Freesurfer recon-all parcellation in a group of 10 patients with heterogeneous gliomatous lesions, and a realistic synthetic cohort of glioma patients (n = 100) derived from healthy control data and patient data. We demonstrate that VBG outperforms a non-VBG approach assessed qualitatively by expert neuroradiologists and Mann-Whitney U tests to compare corresponding parcellations (real patients U(6,6) = 33, z = 2.738, P < .010, synthetic-patients U(48,48) = 2076, z = 7.336, P < .001). Results were also quantitatively evaluated by comparing mean dice scores from the synthetic-patients using one-way ANOVA (unilateral VBG = 0.894, bilateral VBG = 0.903, and non-VBG = 0.617, P < .001). Additionally, we used linear regression to show the influence of lesion volume, lesion overlap with, and distance from the Freesurfer volumes of interest, on labeling accuracy. VBG may benefit the neuroimaging community by enabling automated state-of-the-art MRI analyses in clinical populations using methods such as FreeSurfer, CAT12, SPM, Connectome Workbench, as well as structural and functional connectomics. To fully maximize its availability, VBG is provided as open software under a Mozilla 2.0 license (https://github.com/KUL-Radneuron/KUL_VBG).

Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus.

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty-four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High-density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta-band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma-band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.

Language Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines.

Numerous studies have shown that language processing is not limited to a few brain areas. Visual or auditory stimuli activate corresponding cortical areas, then memory identifies the word or image, Wernicke's and Broca's areas support the processing for either reading/listening or speaking and many areas of the brain are recruited. Determining how a normal person processes language helps clinicians and scientist to understand how brain pathologies such as tumor or stroke can affect changes in language processing. Patients with epilepsy may develop atypical language organization. Over time, the chronic nature of epileptic activity, or changes from a tumor or stroke, can result in a shift of language processing area from the left to the right hemisphere, or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. It is important to determine where these language areas are prior to brain surgery. MEG evoked responses reflecting cerebral activation of receptive and expressive language processing can be localized using several different techniques: Single equivalent current dipole, current distribution techniques or beamformer techniques. Over the past 20 years there have been at least 25 validated MEG studies that indicate MEG can be used to determine the dominant hemisphere for language processing. The use of MEG neuroimaging techniques is needed to reliably predict altered language networks in patients and to provide identification of language eloquent cortices for localization and lateralization necessary for clinical care.

Topics and trends in artificial intelligence assisted human brain research.

Artificial intelligence (AI) assisted human brain research is a dynamic interdisciplinary field with great interest, rich literature, and huge diversity. The diversity in research topics and technologies keeps increasing along with the tremendous growth in application scope of AI-assisted human brain research. A comprehensive understanding of this field is necessary to assess research efficacy, (re)allocate research resources, and conduct collaborations. This paper combines the structural topic modeling (STM) with the bibliometric analysis to automatically identify prominent research topics from the large-scale, unstructured text of AI-assisted human brain research publications in the past decade. Analyses on topical trends, correlations, and clusters reveal distinct developmental trends of these topics, promising research orientations, and diverse topical distributions in influential countries/regions and research institutes. These findings help better understand scientific and technological AI-assisted human brain research, provide insightful guidance for resource (re)allocation, and promote effective international collaborations.

A decade of infant neuroimaging research: What have we learned and where are we going?

The past decade has seen the emergence of neuroimaging studies of infant populations. Incorporating imaging has resulted in invaluable insights about neurodevelopment at the start of life. However, little has been enquired of the experimental specifications and study characteristics of typical findings. This review systematically screened empirical studies that used electroencephalography (EEG), magnetoencephalography (MEG), functional near-infrared spectroscopy (fNIRS), and functional magnetic resonance imaging (fMRI) on infants (max. age of 24 months). From more than 21,000 publications, a total of 710 records were included for analyses. With the exception of EEG studies, infant studies with MEG, fNIRS, and fMRI were most often conducted around birth and at 12 months. The vast majority of infant studies came from North America, with very few studies conducted in Africa, certain parts of South America, and Southeast Asia. Finally, longitudinal neuroimaging studies were inclined to adopt EEG, followed by fMRI, fNIRS, and MEG. These results show that there is compelling need for studies with larger sample sizes, studies investigating a broader range of infant developmental periods, and studies from under- and less-developed regions in the world. Addressing these shortcomings in the future will provide a more representative and accurate understanding of neurodevelopment in infancy.

Aberrant regional homogeneity in post-traumatic stress disorder after traffic accident: A resting-state functional MRI study.

OBJECTIVES: The present study explored the changes in spontaneous regional activity in post-traumatic stress disorder (PTSD) patients, who experienced severe traffic accidents. METHODS: 20 drug-naive PTSD patients and 18 healthy control subjects were imaged using resting-state functional magnetic resonance imaging (rs-fMRI) and analyzed by the algorithm of regional homogeneity (ReHo). RESULTS: Compared to the healthy control group, the PTSD group showed decreased ReHo values in the right angular gyrus. In addition, a negative correlation was found between the activity level of the angular gyrus and the CAPS score. CONCLUSION: The dysfunctions were found in the memory- and emotion-related areas, suggested a possible mechanism of memory dysregulation that might be related to the intrusive memory symptoms of PTSD. These results provided imaging evidence that might provide an in-depth understanding of the intrinsic functional architecture of PTSD.

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling.

Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n = 102, age range = 30-89 years) with MRI and Aß PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aß deposition. In addition to carrying out surface-based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aß deposition occurred across the entire cortical topography, increased Aß deposition was especially pronounced toward higher-order transmodal regions. Age-related atrophy was greater toward the posterior end of the hippocampal long-axis. No significant effect of age on Aß deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography-specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain-based biomarkers of aging.