Left-hemispheric Brain Lesions Research Articles

Iowa Brain-Behavior Modeling Toolkit: An Open-Source MATLAB Tool for Inferential and Predictive Modeling of Imaging-Behavior and Lesion-Deficit Relationships.

The traditional analytical framework taken by neuroimaging studies in general, and lesion-behavior studies in particular, has been inferential in nature and has focused on identifying and interpreting statistically significant effects within the sample under study. While this framework is well-suited for hypothesis testing approaches, achieving the modern goal of precision medicine requires a different framework that is predictive in nature and that focuses on maximizing the predictive power of models and evaluating their ability to generalize beyond the data that were used to train them. However, few tools exist to support the development and evaluation of predictive models in the context of neuroimaging or lesion-behavior research, creating an obstacle to the widespread adoption of predictive modeling approaches in the field. Further, existing tools for lesion-behavior analysis are often unable to accommodate categorical outcome variables and often impose restrictions on the predictor data. Researchers therefore often must use different software packages and analytical approaches depending on (a) whether they are addressing a classification versus regression problem and (b) whether their predictor data correspond to binary lesion images, continuous lesion-network images, connectivity matrices, or other data modalities. To address these limitations, we have developed a MATLAB software toolkit that supports both inferential and predictive modeling frameworks, accommodates both classification and regression problems, and does not impose restrictions on the modality of the predictor data. The toolkit features both a graphical user interface and scripting interface, includes implementations of multiple mass-univariate, multivariate, and machine learning models, features built-in and customizable routines for hyper-parameter optimization, cross-validation, model stacking, and significance testing, and automatically generates text-based descriptions of key methodological details and modeling results to improve reproducibility and minimize errors in the reporting of methods and results. Here, we provide an overview and discussion of the toolkit's featuresand demonstrate its functionality by applying it to the question of how expressive and receptive language impairments relate to lesion location, structural disconnection, and functional network disruption in a large sample of patients with left hemispheric brain lesions. We find that impairments in expressive versus receptive language are most strongly associated with left lateral prefrontal and left posterior temporal/parietal damage, respectively. We also find that impairments in expressive vs. receptive language are associated with partially overlapping patterns of fronto-temporal structural disconnection and with similar functional networks. Importantly, we find that lesion location and lesion-derived network measures are highly predictive of both types of impairment, with predictions from models trained on these measures explaining ~30%-40% of thevariance on average when applied to data from patients not used to train the models. We have made the toolkit publicly available,and we have included a comprehensive set of tutorial notebooks to support new users in applying the toolkitintheir studies.

Iowa Brain-Behavior Modeling Toolkit: An Open-Source MATLAB Tool for Inferential and Predictive Modeling of Imaging-Behavior and Lesion-Deficit Relationships.

The traditional analytical framework taken by neuroimaging studies in general, and lesion-behavior studies in particular, has been inferential in nature and has focused on identifying and interpreting statistically significant effects within the sample under study. While this framework is well-suited for hypothesis testing approaches, achieving the modern goal of precision medicine requires a different framework that is predictive in nature and that focuses on maximizing the predictive power of models and evaluating their ability to generalize beyond the data that were used to train them. However, few tools exist to support the development and evaluation of predictive models in the context of neuroimaging or lesion-behavior research, creating an obstacle to the widespread adoption of predictive modeling approaches in the field. Further, existing tools for lesion-behavior analysis are often unable to accommodate categorical outcome variables and often impose restrictions on the predictor data. Researchers therefore often must use different software packages and analytical approaches depending on whether they are addressing a classification vs. regression problem and on whether their predictor data correspond to binary lesion images, continuous lesion-network images, connectivity matrices, or other data modalities. To address these limitations, we have developed a MATLAB software toolkit that supports both inferential and predictive modeling frameworks, accommodates both classification and regression problems, and does not impose restrictions on the modality of the predictor data. The toolkit features both a graphical user interface and scripting interface, includes implementations of multiple mass-univariate, multivariate, and machine learning models, features built-in and customizable routines for hyper-parameter optimization, cross-validation, model stacking, and significance testing, and automatically generates text-based descriptions of key methodological details and modeling results to improve reproducibility and minimize errors in the reporting of methods and results. Here, we provide an overview and discussion of the toolkit features and demonstrate its functionality by applying it to the question of how expressive and receptive language impairments relate to lesion location, structural disconnection, and functional network disruption in a large sample of patients with left hemispheric brain lesions. We find that impairments in expressive vs. receptive language are most strongly associated with left lateral prefrontal and left posterior temporal/parietal damage, respectively. We also find that impairments in expressive vs. receptive language are associated with partially overlapping patterns of fronto-temporal structural disconnection, and that the associated functional networks are also similar. Importantly, we find that lesion location and lesion-derived network measures are highly predictive of both types of impairment, with predictions from models trained on these measures explaining ~30-40% of the variance on average when applied to data from patients not used to train the models. We have made the toolkit publicly available, and we have included a comprehensive set of tutorial notebooks to support new users in applying the toolkit in their studies.

An immersive virtual reality tool for assessing left and right unilateral spatial neglect.

The reported rate of the occurrence of unilateral spatial neglect (USN) is highly variable likely due to the lack of validity and low sensitivity of classical tools used to assess it. Virtual reality (VR) assessments try to overcome these limitations by proposing immersive and complex environments. Nevertheless, existing VR-based tasks are mostly focused only on near space and lack analysis of psychometric properties and/or clinical validation. The present study evaluates the clinical validity and sensitivity of a new immersive VR-based task to assess USN in the extra-personal space and examines the neuronal correlates of deficits of far space exploration. The task was administrated to two groups of patients with right (N = 28) or left (N = 11) hemispheric brain lesions, also undergoing classical paper-and-pencil assessment, as well as a group of healthy participants. Our VR-based task detected 44% of neglect cases compared to 31% by paper-and-pencil tests in the total sample. Importantly, 30% of the patients (with right or left brain lesions) with no clear sign of USN on the paper-and-pencil tests performed outside the normal range in the VR-based task. Voxel lesion-symptom mapping revealed that deficits detected in VR were associated with lesions in insular and temporal cortex, part of the neural network involved in spatial processing. These results show that our immersive VR-based task is efficient and sensitive in detecting mild to strong manifestations of USN affecting the extra-personal space, which may be undetected using standard tools.

Atypical language organization following perinatal infarctions of the left hemisphere is associated with structural changes in right-hemispheric grey matter.

To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere. This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right-hemispheric grey matter group differences by voxel-based morphometry (VBM). FMRI revealed left-dominance in seven patients with typical language organization (TYP) and right-dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel-based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. Compatible with a non-specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization. Perinatal stroke leads to decreased grey matter in the contralesional hemisphere. Atypical language organization is associated with grey matter increases in contralesional language areas.

BONEs not CATs attract DOGs: Semantic context effects for picture naming in the lesioned language network

The breakdown of rapid and accurate retrieval of words is a hallmark of aphasic speech and a prime target of therapeutic intervention. Complementary, psycho- and neurolinguistic research have developed a spectrum of models, how and by which neuronal network uncompromised speakers can rely on remarkable lexical retrieval capacities. Motivated by both lines of research we invited 32 participants with a chronic left hemispheric brain lesion to name pictures in the presence of distractor words. This picture-word-interference (PWI) paradigm is widely used in psycho- and neurolinguistic research.We find that also after brain lesion categorically related words (CAT → [dog]picture) impede naming, while associatively related words (BONE → [dog]picture) ease access, when compared to unrelated distractor words. The effects largely affecting latencies in neurotypical populations, are reproduced for error rate in our participants with lesions in the language network. Unsurprisingly, overall naming abilities varied greatly across patients. Notably, however, the two effects (categorical interference / associative facilitation) differ between participants. Correlating performance with lesion patterns we find support for the notion of a divergence of brain areas affording different aspects of the task: (i) lesions in the left middle temporal gyurs (MTG) deteriorate overall naming, confirming previous work; more notably, (ii) lesions comprising the inferior frontal hub (inferior frontal gyrus, IFG) of the language-network increase the interference effect for the categorical condition; on the contrary, (iii) lesions to the mid-to-posterior temporal hub (posterior middle and superior temporal gyri, pMTG/ pSTG) increase the facilitatory effect for the associative condition on error rates.The findings can be accommodated in a neuro-linguistic framework, which localizes lexical activation but also lexical interference in posterior parts of the language network (pMTG/pITG); conversely, selection between co-activated categorically related entries is afforded by frontal language areas (IFG). While purely experimental in nature our study highlights that lesion site differentially influences specific aspects of word retrieval. Since confrontational naming is a cornerstone of aphasia rehabilitation, this may be of note when designing and evaluating novel therapeutic regimes.

Intensive Communicative Therapy Reduces Symptoms of Depression in Chronic Nonfluent Aphasia

Background. Patients with brain lesions and resultant chronic aphasia frequently suffer from depression. However, no effective interventions are available to target neuropsychiatric symptoms in patients with aphasia who have severe language and communication deficits. Objective. The present study aimed to investigate the efficacy of 2 different methods of speech and language therapy in reducing symptoms of depression in aphasia on the Beck Depression Inventory (BDI) using secondary analysis (BILAT-1 trial). Methods. In a crossover randomized controlled trial, 18 participants with chronic nonfluent aphasia following left-hemispheric brain lesions were assigned to 2 consecutive treatments: (1) intensive language-action therapy (ILAT), emphasizing communicative language use in social interaction, and (2) intensive naming therapy (INT), an utterance-centered standard method. Patients were randomly assigned to 2 groups, receiving both treatments in counterbalanced order. Both interventions were applied for 3.5 hours daily over a period of 6 consecutive working days. Outcome measures included depression scores on the BDI and a clinical language test (Aachen Aphasia Test). Results. Patients showed a significant decrease in symptoms of depression after ILAT but not after INT, which paralleled changes on clinical language tests. Treatment-induced decreases in depression scores persisted when controlling for individual changes in language performance. Conclusions. Intensive training of behaviorally relevant verbal communication in social interaction might help reduce symptoms of depression in patients with chronic nonfluent aphasia.

Lesion characteristics driving right-hemispheric language reorganization in congenital left-hemispheric brain damage

Pre- or perinatally acquired (“congenital”) left-hemispheric brain lesions can be compensated for by reorganizing language into homotopic brain regions in the right hemisphere. Language comprehension may be hemispherically dissociated from language production. We investigated the lesion characteristics driving inter-hemispheric reorganization of language comprehension and language production in 19 patients (7–32years; eight females) with congenital left-hemispheric brain lesions (periventricular lesions [n=11] and middle cerebral artery infarctions [n=8]) by fMRI. 16/17 patients demonstrated reorganized language production, while 7/19 patients had reorganized language comprehension. Lesions to the insular cortex and the temporo-parietal junction (predominantly supramarginal gyrus) were significantly more common in patients in whom both, language production and comprehension were reorganized. These areas belong to the dorsal stream of the language network, participating in the auditory-motor integration of language. Our data suggest that the integrity of this stream might be crucial for a normal left-lateralized language development.

Processing verbal morphology in patients with congenital left-hemispheric brain lesions

The goal of this study was to test whether children, teenagers and adults with congenital left-hemispheric brain lesions master the regularities of German verbal inflectional morphology. Thirteen patients and 35 controls without brain damage participated in three experiments. A grammaticality judgment task, a participle inflection task and a nonce-verb inflection task revealed significant differences between patients and controls. In addition, a main effect of verb type could be observed as patients and controls made more mistakes with irregular than with regular verbs. The findings indicate that the congenitally damaged brain not only has difficulties with complex syntactic structures during language development, as reported by earlier studies, but also has persistent deficits on the morphological level. These observations suggest that the plasticity of the developing brain cannot fully compensate for congenital brain damage which affects regions associated with language functions.

Role of serum Neuron Specific Enolase in differentiating the side of brain lesion in acute ischemic stroke

Objectives: The aim of this study is to see the role of serum NSE (Neuron Specific Enolase) as a neuronal damage marker and in differentiating the side of brain lesion in acute ischemic stroke patients. Methods: A total of 35 acute ischemic stroke patients (clinically and radiologically confirmed) irrespective of age and sex, admitted in Emergency Unit, Medicine Department within 24 hours of stroke onset were included in this study. Plain CT scan or MRI brain was done for all these patients on admission and after 48 hours to confirm the diagnosis and the side of the lesion in brain. Serum NSE was estimated by using NSE Human ELISA Kit, in the Department of Physiology. Results: In this study, serum NSE bears a positive significant correlation to the infarct volume in brain (r=0.783, p<0.001) and to the National Institute of Health Stroke Scale (NIHSS) (r=0.538, p=0.001). However, there is no significance difference between the serum NSE in right hemispheric brain lesion compared to left hemispheric brain lesion (p=0.596). Conclusions: Serum NSE within 24 hours of stroke onset can reflect the volume of brain lesion and severity of acute stroke but cannot differentiate the side of brain lesion in these patients.

The ventral fiber pathway for pantomime of object use

The current concept of a dual loop system of brain organization predicts a domain-general dual-pathway architecture involving dorsal and ventral fiber connections. We investigated if a similar dichotomy of brain network organization applies for pantomime (P) and imitation of meaningless gestures (I). Impairments of these tasks occur after left hemispheric brain lesions causing apraxia. Isolated impairments and double-dissociations point towards an anatomical segregation. Frontal and parietal areas seem to contribute differently. A special role of the inferior frontal gyrus and underlying fiber pathways was suggested recently.Using a combined fMRI/DTI-approach, we compared the fiber pathway architecture of left hemispheric frontal, temporal and parietal network components of pantomime and imitation. Thereby, we separated object effects from pantomime-specific effects. P and I both engage a fronto-temporo-parietal network of cortical areas interconnected by a dorsal fiber system (superior longitudinal fascicle) for direct sensory–motor interactions. The pantomime-specific effect additionally involved the triangular part of the inferior frontal gyrus, the middle temporal gyrus, the inferior parietal cortex and the intraparietal sulcus, interconnected by ventral fibers of the extreme capsule, likely related to higher-order conceptual and semantic operations. We discuss this finding in the context of the dual loop model and recent anatomical concepts.

Past Tense in Children with Focal Brain Lesions

In this study, 22 children with early left hemisphere (LHD) or right hemisphere (RHD) focal brain lesions (FL, n ¼ 14 LHD, n ¼ 8 RHD) were administered an English past tense elicitation test (M ¼ 6:5 years). Proportion correct and frequency of overregularization and zero-marking errors were compared to age-matched samples of children with specific language impairment (SLI, n ¼ 27) and with typical language development (TD, n ¼ 27). Similar rates of correct production and error patterns were observed for the children with TD and FL; whereas, children with SLI produced more zero-marking errors than either their FL or TD peers. Performance was predicted by vocabulary level (PPVT-R) for children in all groups, and errors did not differ as a function of lesion side (LHD vs. RHD). Findings are discussed in terms of the nature of brain–language relations and how those relationships develop over the course of language learning.

Early left-hemispheric brain lesions: When is Language Comprehension Reorganized?

Aims: Early lesions of the left hemisphere (LH) induce reorganization of the productive language network to the right hemisphere, if a) anterior language cortex or b) the facial motor tracts are damaged. One of the first steps in the acquisition of speech and language production is the production of speech sounds, where the facial motor tracts play a crucial role. It is still unclear, however, which structures are relevant for LH processing of language comprehension in children with congenital LH brain lesions. We conducted a lesion-symptom-mapping study to identify brain structures possibly triggering the reorganisation of language comprehension if damaged early in brain development.

The neural correlates of impaired collision avoidance in hemianopic patients

The aim of this study was to assess the brain regions associated with impaired performance in a virtual, dynamic collision avoidance task, in a group of patients with homonymous visual field defects (HVFDs) because of unilateral vascular brain lesions. Overall task performance was quantitatively assessed as the number of collisions while crossing an intersection at two levels of traffic density. Twenty-six patients were divided into two subgroups using the median split method: patients with 'performance above average' (HVFD(A), i.e. lower number of collisions) and patients with 'performance below average' (HVFD(B), i.e. higher number of collisions). In order to identify the anatomical structures that might be specifically affected in HVFD(B) patients but spared in HVFD(A) patients, overlap, subtraction and voxel-based lesion-symptom mapping analyses were performed using the MRIcron software. No significant difference in collision avoidance between patients with left- and right-hemispheric lesions was revealed. Separate lesion analysis in 12 patients with right- and 14 patients with left-hemispheric lesions showed that the cortical structures associated with impaired collision avoidance were the parieto-occipital region and posterior cingulate gyrus in the right hemisphere and the inferior occipital cortex and parts of the fusiform (occipito-temporal) gyrus in the left hemisphere. In the present collision avoidance paradigm, impaired performance of patients with right-hemispheric lesions is associated with damage in the dorsal processing stream and potential impact on the visual spatial working memory (WM), while impaired performance of patients with left-hemispheric lesions is associated with damage in the ventral stream and potential impact on the visual object WM.

IFNβ-1b may severely exacerbate Japanese opticspinal MS in neuromyelitis optica spectrum: Japanese optic-spinal MS: Is it MS or neuromyelitis optica and does the answer dictate treatment?

# {#article-title-2} To the Editor: Shimizu et al.1 report increased demyelination and inflammation following interferon-β-1b (IFNβ-1b) therapy in patients with opticospinal multiple sclerosis (OSMS) and neuromyelitis optica (NMO). In the accompanying editorial, Drs. Weinshenker and Wingerchuk2 discuss whether a shift of immune response secondary to treatment with IFNβ-1b may account for the unpredictable response. We contend that the offset of immune response capable of unpredictable demyelinating attacks is unknown and not necessarily confined to B-cell activity or Th2 shift. A 42-year-old Caucasian woman had, over the course of 6 months, 2 episodes of optic neuritis—one in each eye—and 2 attacks to the spinal cord consistent with acute recurrent myelitis. The MRI brain showed no signs of demyelination and, despite negative NMO–immunoglobulin G (IgG), the patient was started on rituximab. Within 2 weeks, she developed a left hemispheric brain lesion similar to the one shown in figure 1A.1 The brain lesion continued to expand and after 6 courses of monthly cyclophosphamide the active process was suppressed. The pathology obtained via brain biopsy revealed reactive hypercellularity with …

Hemispheric asymmetries in the resting-sate functional connectivity patterns of the brain regions critical for language comprehension

Hemispheric asymmetries in the resting-sate functional connectivity patterns of the brain regions critical for language comprehension

Reorganization after pre‐ and perinatal brain lesions*

The developing human brain can compensate for pre- and perinatally acquired focal lesions more effectively than the adult brain. The mechanisms by which this effective reorganization is achieved vary considerably between different functional systems, reflecting differences in the normal maturation of these systems. In the motor system, descending cortico-spinal motor projections have already reached their spinal target zones at the beginning of the third trimester of pregnancy, with initially bilateral projections from each hemisphere. During normal development, the ipsilateral projections are gradually withdrawn, whereas the contralateral projections persist. When, during this period, a unilateral brain lesion disrupts the cortico-spinal projections of one hemisphere, the ipsilateral projections from the contralesional hemisphere will persist. This allows the contralesional hemisphere to take over motor control over the paretic extremities. Although this mechanism of reorganization is available throughout the pre- and perinatal period, the efficacy of this ipsilateral takeover of motor functions decreases with increasing age at the time of the insult. In the somatosensory system, ascending thalamo-cortical somatosensory projections have not yet reached their cortical target zones at the beginning of the third trimester of pregnancy. Therefore, these projections can still 'react' to brain lesions acquired during this period, and can form 'axonal bypasses' around periventricular white matter lesions to reach their original cortical target areas in the postcentral gyrus. Thus, somatosensory functions can be well preserved even in cases of large periventricular lesions. In contrast, when the postcentral gyrus itself is affected, no signs for reorganization have been observed. Accordingly, somatosensory functions are often poor in these patients. Language functions can be normal even in patients with extensive early left-hemispheric brain lesions. This is achieved by language organization in the right hemisphere, which takes place in brain regions homotopic to the classical left-hemispheric language areas in normal subjects. In patients with periventricular lesions, the degree of right-hemispheric takeover of language functions correlates with the severity of structural damage to facial (and, thus, articulatory) motor projections.

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries.

Reorganization of the cerebro-cerebellar network of language production in patients with congenital left-hemispheric brain lesions

Patients with congenital lesions of the left cerebral hemisphere may reorganize language functions into the right hemisphere. In these patients, language production is represented homotopically to the left-hemispheric language areas. We studied cerebellar activation in five patients with congenital lesions of the left cerebral hemisphere to assess if the language network is reorganized completely in these patients, i.e. including also cerebellar language functions. As compared to a group of controls matched for age, sex, and verbal IQ, the patients recruited an area not in the right but in the left cerebellar hemisphere. The extent of laterality of the cerebellar activation correlated significantly with the laterality of the frontal activation. We suggest that the developing brain reacts to early focal lesions in the left hemisphere with a mirror-image organization of the entire cerebro-cerebellar network engaged in speech production.

Direct Demonstration of Transcallosal Disinhibition in Language Networks

Neuroimaging studies in right-handed patients with left hemisphere brain lesions have demonstrated a shift of language activity from left to right inferior frontal gyrus (IFG). This shift may be caused by greater right hemisphere dominance before the injury or by reduced inhibitory activity of the injured left hemisphere. We simulated a brain lesion applying transcranial -magnetic stimulation over left IFG in normal subjects, while simultaneously measuring language activity with positron -emission tomography. Interference with transcranial -magnetic stimulation decreased activity in left and increased it in right IFG in all subjects. We thus demonstrate for the first time that a rightward shift of language activity is caused by the brain lesion and not by greater right-hemisphere dominance, thus supporting the hypothesis of reduced transcallosal inhibition.

Lesion-induced right-hemispheric language and organization of nonverbal functions

Early left-hemispheric brain lesions may lead to a reorganization of language into the right hemisphere. Language functions are consecutively spared, but visuospatial functions show slight deficits. Cortical 'crowding' of the right hemisphere has been suggested as an explanation for this effect, but no direct evidence has as yet been put forward. We examined six patients with early left-hemispheric brain lesions and subsequent right-hemispheric language organization with functional magnetic resonance imaging and compared their activation patterns in a verbal and two nonverbal tasks with the patterns of six controls. In the patient group, nonverbal functions were reorganized neither interhemispherically nor intrahemispherically. Instead, verbal and nonverbal functions were mediated by a common right-hemispheric network. This argues in favour of the 'crowding hypothesis'.