Lesion-based Studies Research Articles

A large public dataset of annotated clinical MRIs and metadata of patients with acute stroke

To extract meaningful and reproducible models of brain function from stroke images, for both clinical and research proposes, is a daunting task severely hindered by the great variability of lesion frequency and patterns. Large datasets are therefore imperative, as well as fully automated image post-processing tools to analyze them. The development of such tools, particularly with artificial intelligence, is highly dependent on the availability of large datasets to model training and testing. We present a public dataset of 2,888 multimodal clinical MRIs of patients with acute and early subacute stroke, with manual lesion segmentation, and metadata. The dataset provides high quality, large scale, human-supervised knowledge to feed artificial intelligence models and enable further development of tools to automate several tasks that currently rely on human labor, such as lesion segmentation, labeling, calculation of disease-relevant scores, and lesion-based studies relating function to frequency lesion maps.

A Propensity Score-Matched Comparison of Midterm Outcomes Between Drug-Coated Balloons and Drug-Eluting Stents for Patients with Acute Coronary Syndrome.

We conducted a single-center, retrospective, lesion-based study to examine the safety and efficacy of drug-coated balloons (DCBs) for de novo coronary stenosis in patients with acute coronary syndrome (ACS) by comparing them with those of drug-eluting stents (DESs).A total of 309 consecutive lesions in patients with ACS who were successfully treated by emergent procedures using either a DCB (n = 107) or a DES between January 2016 and December 2019 were included in the study. The primary endpoint was the incidence of target lesion failure (TLF), defined as cardiac death without mortality due to ACS, non-fatal myocardial infarction, and any target lesion revascularization, including acute occlusion, after DCB use and definite stent thrombosis after DES placement. A propensity score-matched analysis was used to adjust the 36 baseline variables. Retrospective investigations were conducted in January 2021.Baseline adjustment yielded 91 lesions in each group, with a mean balloon size of 3.02 ± 0.22 mm and a mean length of 20.9 ± 6.2 mm in the DCB group. The frequency of TLF in the DCB group (9.9% during the mean observational interval of 671 ± 508 days) was not significantly different from that in the DES group (13.2% during a period of 626 ± 543 days, P = 0.467). The cumulative TLF-free ratio in the DCB group was not significantly different from that in the DES group (P = 0.475, log-rank test).The present propensity score-matched comparison showed statistically equivalent midterm clinical outcomes after DCB use to those of DES placement for de novo lesions in patients with ACS treated by emergent procedures.

Chapter 8 - The role of disrupted structural connectivity in aphasia

Lesion-based studies are among the most informative approaches to determine a critical relationship between a particular brain region and specific function. Importantly, brain lesions cause disconnection of other brain areas that appear to be intact and may cause functional deficits in these regions due to a lack of afferent projections. If only the location of necrosis and gliosis after the stroke is considered to be the lesion, the full spectrum of brain dysfunction is only partly assessed, and there is a high probability that incomplete region-to-function inferences are made. In this chapter we (1) outline how structural connectivity can be measured in individuals with stroke, and (2) provide an overview of the importance of disrupted structural connectivity in aphasia. We conclude that connection-based and region/voxel-based symptom mapping yield complementary information and together provide an in-depth picture of brain and function relationships.

Role of the dorsal attention network in distracter suppression based on features

ABSTRACTSelective attention allows us to prioritize the processing of relevant information and filter out irrelevant information. Human functional neuroimaging and lesion-based studies have highlighted the fronto-parietal dorsal attention network (DAN) as an important network in this process. In this study, we investigated the role of the DAN in distracter suppression by dynamically modifying the priority of visual information (target > high priority distracter > low priority distracter) based on features only. To this end, we collected fMRI data in 24 healthy subjects, who performed a feature-based variant of the sustained attention to response task. Participants had to select one or attend two stream(s) of overlapping digits that differed in color and respond to each digit in the task-relevant stream(s) except to a single non-target digit. Results showed higher DAN activity when a target was co-presented with a high versus low priority distracter. Furthermore, higher DAN activity was observed when selectively attending one (target + high/low priority distracter) versus simultaneously attending two (target + target) stream(s) of digits. In conclusion, our study highlights the contribution of the DAN in the feature-based suppression of task-irrelevant information.

Neural organization of speech production: A lesion-based study of error patterns in connected speech

While numerous studies have explored single-word naming, few have evaluated the behavioral and neural correlates of more naturalistic language, like connected speech, which we produce every day. Here, in a retrospective analysis of 120 participants at least six months following left hemisphere stroke, we evaluated the distribution of word errors (paraphasias) and associated brain damage during connected speech (picture description) and object naming. While paraphasias in connected speech and naming shared underlying neural substrates, analysis of the distribution of paraphasias suggested that lexical-semantic load is likely reduced during connected speech. Using voxelwise lesion-symptom mapping (VLSM), we demonstrated that verbal (real word: semantically related and unrelated) and sound (phonemic and neologistic) paraphasias during both connected speech and naming loaded onto the left hemisphere ventral and dorsal streams of language, respectively. Furthermore, for the first time using both connected speech and naming data, we localized semantically related paraphasias to more anterior left hemisphere temporal cortex and unrelated paraphasias to more posterior left temporal and temporoparietal cortex. The connected speech results, in particular, highlight a gradient of specificity as one translates visual recognition from left temporo-occipital cortex to posterior and subsequently anterior temporal cortex. The robustness of VLSM results for sound paraphasias derived during connected speech was notable, in that analyses performed on sound paraphasias from the connected speech task, and not the naming task, demonstrated significant results following removal of lesion volume variance and related apraxia of speech variance. Therefore, connected speech may be a particularly sensitive task on which to evaluate further lexical-phonological processing in the brain. The results presented here demonstrate the related, though different, distribution of paraphasias during connected speech, confirm that paraphasias arising in connected speech and single-word naming likely share neural origins, and endorse the need for continued evaluation of the neural substrates of connected speech processes.

Estimating effects of graded white matter damage and binary tract disconnection on post-stroke language impairment

Despite the critical importance of close replications in strengthening and advancing scientific knowledge, there are inherent challenges to conducting replications of lesion-based studies. In the present study, we conducted a close conceptual replication of a study (i.e., Hope et al., 2016) that found that fluency and naming scores in post-stoke aphasia were more strongly associated with a binary measure of structural white matter integrity (tract disconnection) than a graded measure (lesion load). Using a different sample of stroke patients (N = 128) and four language deficit measures (aphasia severity, picture naming, and composite scores for speech production and semantic cognition), we examined tract disconnection and lesion load in three white matter tracts that have been implicated in language processing: arcuate fasciculus, uncinate fasciculus, and inferior fronto-occipital fasciculus. We did not find any consistent evidence that binary tract disconnection was more strongly associated with language impairment over and above lesion load, though individual deficit measures differed with respect to whether lesion load or tract disconnection was the stronger predictor. Given the mixed findings, we suggest caution when using such indirect estimates of structural white matter integrity, and direct individual measurements (for example, using diffusion weighted imaging) should be preferred when they are available. We end by highlighting the complex nature of replication in lesion-based studies and offer some potential solutions.

The lonely brain: evidence from studying patients with penetrating brain injury

ABSTRACTLoneliness is perceived as social isolation and exclusion. The neural substrate of loneliness has been investigated with functional neuroimaging; however, lesion-based studies and their associated outcomes are needed to infer causal involvement between brain regions and function. Here, we applied voxel-based lesion-symptom mapping (VLSM) analyses to investigate the causal role of brain lesions on self-report of loneliness (UCLA Loneliness Scale) in a unique sample from the Vietnam Head Injury Study, including veterans with penetrating traumatic brain injuries (pTBI) (n = 132) and healthy controls (HCs) (n = 35). Our results revealed that the right anterior insula (AI) and right prefrontal cortex (PFC) are key brain regions underpinning loneliness perception. Individuals with selective lesions to the right AI and right PFC were less likely to report loneliness compared to patients with selective lesions to the posterior cortex and HCs. Therefore, it appears that lesions to key regions involved in processing social pain act to lower the perception of loneliness. Reporting loneliness was associated with executive dysfunction, apathy, disinhibition, and lower life satisfaction. In conclusion, the reported findings broaden our understanding of how loneliness is processed in the social brain, and how behavioral and cognitive factors can influence this perception.

Neural networks supporting audiovisual integration for speech: A large-scale lesion study

Auditory and visual speech information are often strongly integrated resulting in perceptual enhancements for audiovisual (AV) speech over audio alone and sometimes yielding compelling illusory fusion percepts when AV cues are mismatched, the McGurk-MacDonald effect. Previous research has identified three candidate regions thought to be critical for AV speech integration: the posterior superior temporal sulcus (STS), early auditory cortex, and the posterior inferior frontal gyrus. We assess the causal involvement of these regions (and others) in the first large-scale (N = 100) lesion-based study of AV speech integration. Two primary findings emerged. First, behavioral performance and lesion maps for AV enhancement and illusory fusion measures indicate that classic metrics of AV speech integration are not necessarily measuring the same process. Second, lesions involving superior temporal auditory, lateral occipital visual, and multisensory zones in the STS are the most disruptive to AV speech integration. Further, when AV speech integration fails, the nature of the failure—auditory vs visual capture—can be predicted from the location of the lesions. These findings show that AV speech processing is supported by unimodal auditory and visual cortices as well as multimodal regions such as the STS at their boundary. Motor related frontal regions do not appear to play a role in AV speech integration.

Temporal lobe networks supporting the comprehension of spoken words.

Auditory word comprehension is a cognitive process that involves the transformation of auditory signals into abstract concepts. Traditional lesion-based studies of stroke survivors with aphasia have suggested that neocortical regions adjacent to auditory cortex are primarily responsible for word comprehension. However, recent primary progressive aphasia and normal neurophysiological studies have challenged this concept, suggesting that the left temporal pole is crucial for word comprehension. Due to its vasculature, the temporal pole is not commonly completely lesioned in stroke survivors and this heterogeneity may have prevented its identification in lesion-based studies of auditory comprehension. We aimed to resolve this controversy using a combined voxel-based-and structural connectome-lesion symptom mapping approach, since cortical dysfunction after stroke can arise from cortical damage or from white matter disconnection. Magnetic resonance imaging (T1-weighted and diffusion tensor imaging-based structural connectome), auditory word comprehension and object recognition tests were obtained from 67 chronic left hemisphere stroke survivors. We observed that damage to the inferior temporal gyrus, to the fusiform gyrus and to a white matter network including the left posterior temporal region and its connections to the middle temporal gyrus, inferior temporal gyrus, and cingulate cortex, was associated with word comprehension difficulties after factoring out object recognition. These results suggest that the posterior lateral and inferior temporal regions are crucial for word comprehension, serving as a hub to integrate auditory and conceptual processing. Early processing linking auditory words to concepts is situated in posterior lateral temporal regions, whereas additional and deeper levels of semantic processing likely require more anterior temporal regions.10.1093/brain/awx169_video1awx169media15555638084001.

Propensity-Score Matched Comparison of Midterm Angiographic Outcomes of Sirolimus- Versus Everolimus- and Biolimus-Eluting Stents for <i>De Novo</i> Coronary Stenosis

We conducted propensity-score matched comparisons of midterm angiographic outcomes of sirolimus (SES) versus either everolimus- (EES) or biolimus- (BES) eluting stents after placements for coronary stenosis in a daily practice environment since previous randomized trials did not demonstrate the superiority of EES and BES over SES in terms of midterm angiographic outcomes.The present study was a non-randomized, retrospective, and lesion-based study, recruiting angiographically followed-up lesions within 550 days after successful and elective SES (n = 1793), EES (n = 1303), or BES (n = 324) placement for de novo native coronary stenosis during the period from August 2004 to January 2014 at 6 institutes. The endpoint, as an angiographic surrogate marker of clinical efficacy, was the distribution of in-stent follow-up percent diameter stenosis (%DS) which comprised the percentages of 1) follow-up %DS < 20 and 2) follow-up %DS > 50. Propensityscore matched analyses were conducted to adjust 21 baselines.In 1215 baseline adjusted lesions, the endpoints in the EES group [1) 74.1%, and 2) 4.6%] were significantly different from those in the SES group [57.9%; P < 0.001, 7.2%; P = 0.006, respectively). In 307 baseline adjusted lesions, the endpoints in the BES group [1) 80.5%, 2) 2.0%] were significantly different from those in the SES group [59.3%; P < 0.001, 2) 8.1%; P = 0.001, respectively].The present study is the first to confirm the superiority of midterm angiographic outcomes after the placement of EES and BES over SES for de novo coronary stenosis in a clinical setting.

Speech repetition as a window on the neurobiology of auditory–motor integration for speech: A voxel-based lesion symptom mapping study

For more than a century, speech repetition has been used as an assay for gauging the integrity of the auditory–motor pathway in aphasia, thought classically to involve a linkage between Wernicke's area and Broca's area via the arcuate fasciculus. During the last decade, evidence primarily from functional imaging in healthy individuals has refined this picture both computationally and anatomically, suggesting the existence of a cortical hub located at the parietal–temporal boundary (area Spt) that functions to integrate auditory and motor speech networks for both repetition and spontaneous speech production. While functional imaging research can pinpoint the regions activated in repetition/auditory–motor integration, lesion-based studies are needed to infer causal involvement. Previous lesion studies of repetition have yielded mixed results with respect to Spt's critical involvement in speech repetition. The present study used voxel-based lesion symptom mapping (VLSM) to investigate the neuroanatomy of repetition of both real words and non-words in a sample of 47 patients with focal left hemisphere brain damage. VLSMs identified a large voxel cluster spanning gray and white matter in the left temporal–parietal junction, including area Spt, where damage was significantly related to poor non-word repetition. Repetition of real words implicated a very similar dorsal network including area Spt. Cortical regions including Spt were implicated in repetition performance even when white matter damage was factored out. In addition, removing variance associated with speech perception abilities did not alter the overall lesion pattern for either task. Together with past functional imaging work, our results suggest that area Spt is integral in both word and non-word repetition, that its contribution is above and beyond that made by white matter pathways, and is not driven by perceptual processes alone. These findings are highly consistent with the claim that Spt is an area of sensory-motor translation in speech processing.

Are executive skills primarily mediated by the prefrontal cortex in childhood? Examination of focal brain lesions in childhood

Introduction Based on the study of adults with brain insult, traditional localizationist views have argued that executive skills are primarily mediated by prefrontal cortex. It remains unclear whether a similar pattern of localization exists in childhood. Methods: To investigate this hypothesis, we compared the performance of children, aged 7–16 years, with radiological evidence of brain pathology. The sample was divided according to lesion location as follows: frontal pathology (n = 38), extra-frontal pathology (n = 20), generalized pathology (n = 21) and healthy controls (n = 40). Using a multidimensional model of executive function described by Anderson (2002) and Anderson (1998; Anderson et al., 2001c, 2001d), these groups were compared on a range of executive function domains including: attentional control, goal setting, cognitive flexibility, and information processing. Additional, non-executive measures were also administered. Results Contrary to adult lesion-based studies, there was little differentiation in executive processes between frontal and extra-frontal groups. Conclusions These results provide support for contemporary models which propose a distributed, but integrated neural network for executive skills, suggesting that the integrity of the entire brain is necessary for adequate executive functions in childhood. Further, focal lesions to any brain region during development may render children vulnerable to a range of executive deficits that would not normally be expected following similar pathology in adulthood.

Angiographic and Procedural Correlates of Stent Thrombosis after Intracoronary Implantation of Drug‐Eluting Stents

Stent thrombosis (ST) following the implantation of drug-eluting stents (DES) remains the major limitation of this new technology. The identification of modifiable correlates of ST may help reduce this catastrophic event. This was a retrospective, single-center, lesion-based study. A cohort of 45 consecutive lesions (35 patients) initially treated with successful DES implantation from May 2003 to February 2005 that re-presented with ST within 12 months was identified. This cohort was compared to a control group of 1,620 unselected lesions (1,187 patients) that were successfully treated with DES implantation and which remained free of ST. Comparison of angiographic and procedural features was made between the ST and no-ST groups, and logistic regression analysis was then performed to identify independent correlates of ST. For the purposes of the study only definite ST events (angiographically or autopsy proven) were considered. Independent angiographic predictors of cumulative ST at 12 months were left anterior descending (LAD) artery (OR: 1.91, CI: 1.01-3.59, P = 0.045), bifurcation (OR: 2.43, CI: 1.06-5.56, P = 0.035), and in-stent restenotic (OR: 2.64, CI: 1.12-6.25, P = 0.027) lesions. Procedural predictors were number of stents per lesion (OR: 2.30, CI: 1.29-4.11, P = 0.005) and intravascular ultrasound (IVUS) guidance (OR: 0.45, CI: 0.24-0.84, P = 0.013). Correlates of subacute events were LAD artery, proximal segment, and lack of IVUS guidance. Correlates of late ST were bifurcation and in-stent restenotic lesions. Angiographic and procedural correlates of subacute and late ST after DES implantation differ. Lack of IVUS guidance was the only modifiable predictor identified. Treatment of bifurcation and restenotic lesions was predictive of late events.