Extreme Capsule Research Articles

White matter architecture of the language network

AbstractThe relevance of anatomical connectivity for understanding of the neural basis of language was recognized in the 19th century, and yet this topic has only recently become the subject of wider research interest. In this paper, I review recent findings on white matter tracts implicated in language: the arcuate fasciculus, superior longitudinal fasciculus, extreme capsule, uncinate fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. The reviewed findings on these tracts were reported in studies that used a variety of methods, from post-mortem dissection and diffusion imaging to intraoperative electrostimulation with awake surgery patients. The emerging picture suggests that there is currently no consensus with regard to the exact number and identity of the tracts supporting language, their origins, trajectories, and terminations, as well as their functional interpretation.

The lion's mane sign: surgical results using the bilateral fronto-orbito-nasal approach in large and giant anterior skull base meningiomas

Concerns about extreme peritumoral edema and its ensuing surgical and perioperative complications led the authors to use the bilateral fronto-orbito-nasal approach to remove midline anterior skull base meningiomas that were larger than 4 cm. The authors hypothesize that extreme vasogenic edema exemplified by finger-like hyperintensities extending into the bifrontal white matter and external capsule and/or the extreme capsule, coined the lion's mane sign (LMS), would help identify patients with a challenging postoperative course. They hypothesize that the LMS would better predict symptomatic postoperative cerebral edema than the edema index (EI). This is an observational case series of 9 patients. The authors noted the grade, pathology, tumor volume, EI, and the presence or absence of the LMS in all tumors. They used the intensive unit care (ICU) length of stay as a nonspecific measure reflecting postoperative symptomatic cerebral edema. Comparisons of edema-related postoperative complications and the EI were made between patients with and without an LMS. Bifrontal hyperintensities, extending into at least three-eighths of the length of the external capsules on T2-weighted MRI, seen in 4 of 9 patients, portended a longer postoperative ICU stay. The presence of an LMS better predicted postoperative complications related to cerebral edema than tumor grade, pathology, volume, or EI. The LMS predicts an increased duration of stay in the ICU after a bilateral fronto-orbito-nasal approach for resection of large and giant anterior skull base meningiomas. Furthermore, the LMS better predicted increased length of stay in the ICU than did the EI.

Fronto-parietal dorsal and ventral pathways in the context of different linguistic manipulations

This study investigates structural connectivity between left fronto-parietal brain regions that were identified in a previous fMRI study which used different linguistic manipulation tasks. Diffusion-weighted images were acquired from 20 volunteers. Structural connectivity between brain regions from the fMRI study was computed using probabilistic fiber tracking. For suprasegmental manipulation, left inferior parietal lobule (IPL) and left inferior frontal gyrus (IFG), pars opercularis, were connected by a dorsal pathway via the arcuate fascicle and superior longitudinal fascicle III. For segmental manipulation, left IPL and IFG, pars triangularis, were connected by a ventral pathway via the middle longitudinal fascicle and the extreme capsule. We conclude that the dorsal pathway provides a route for mapping from phonological memory in IPL to the inferior frontal articulatory network while the ventral pathway could facilitate the modulation of phonological units based on lexical-semantic aspects, mediate the complexity of auditory objects and the unification of actor-event schemata.

Interactions between White Matter Asymmetry and Language during Neurodevelopment

The human brain is asymmetric in gross structure as well as functional organization. However, the developmental basis and trajectory of this asymmetry is unclear, and its relationship(s) to functional and cognitive development, especially language, remain to be fully elucidated. During infancy and early childhood, in concert with cortical gray matter growth, underlying axonal bundles become progressively myelinated. This myelination is critical for efficient and coherent interneuronal communication and, as revealed in animal studies, the degree of myelination changes in response to environment and neuronal activity. Using a novel quantitative magnetic resonance imaging method to investigate myelin content in vivo in human infants and young children, we investigated gross asymmetry of myelin in a large cohort of 108 typically developing children between 1 and 6 years of age, hypothesizing that asymmetry would predict language abilities in this cohort. While asymmetry of myelin content was evident in multiple cortical and subcortical regions, language ability was predicted only by leftward asymmetry of caudate and frontal cortex myelin content and rightward asymmetry in the extreme capsule. Importantly, the influence of this asymmetry was found to change with age, suggesting an age-specific influence of structure and myelin on language function. The relationship between language ability and asymmetry of myelin stabilized at ∼4 years, indicating anatomical evidence for a critical time during development before which environmental influence on cognition may be greatest.

Action semantics and movement characteristics engage distinct processing streams during the observation of tool use

The cortical motor system follows a modular organization in which different features of executed movements are supported by distinct streams. Accordingly, different levels of action recognition, such as movement characteristics or action semantics may be processed within distinct networks. The present study aimed to differentiate areas related to the analysis of action features involving semantic knowledge from regions concerned with the evaluation of movement characteristics determined by structural object properties. To this end, the assessment of (i) tool-associated actions in relation to semantically, but not functionally inappropriate recipients (factor "Semantics"), and the evaluation of (ii) tool-associated movements performed with awkward versus correct hand postures (factor "Hand") were experimentally manipulated in an fMRI study with an event-related 2 × 2 factorial design. The videos used as stimuli displayed actions performed with the right hand in third-person perspective. Conjunction analysis of all four experimental conditions showed that observing videos depicting tool-related actions compared to rest was associated with widespread bilateral activity within the frontal lobes, inferior and superior parietal lobules, parts of the temporal lobes, as well as the occipital lobes. Viewing actions executed with incorrect compared to correct hand postures (factor "Hand") elicited significantly more activity within right primary sensory cortex (Brodmann area 2) and superior parietal lobule. Conversely, tool-associated actions displayed after semantically incorrect compared to correct recipients elicited higher activation within a left-lateralized network comprising the ventro-lateral prefrontal cortex (VLPFC), parts of the intraparietal sulcus and the angular gyrus (AG), as well as the supplementary motor area (SMA) and pre-SMA. Probabilistic diffusion tensor imaging-based tractography revealed two distinct fiber connections between AG and the frontal activation: A dorsal pathway via the superior longitudinal fascicle to the caudal part of VLPFC and a ventral pathway reaching the more rostral parts of VLPFC via the extreme capsule. The task-dependent relative modulation of activity within these brain networks composed of activated cortical areas connected by specific white matter tracts may indicate that the assessment of semantic action features relies on both dorso-ventral and ventral processing streams, whereas the analysis of hand postures with respect to objects depends on areas within the dorso-dorsal stream.

Language Comprehension in Young People with Severe Cerebral Palsy in Relation to Language Tracts: A Diffusion Tensor Imaging Study

Patients with severe cerebral palsy (CP) often have poor speech ability but potentially better language comprehension. The arcuate fasciculus and the extreme capsule are two important language tracts between the Wernicke and Broca areas. Using diffusion tensor imaging, we visualized language tracts and pyramidal tracts in both hemispheres in 10 controls (5 to 18 years) and 5 patients (5 to 23 years) with severe CP. Language comprehension was assessed with a recently designed instrument (the Computer-Based instrument for Low motor Language Testing [C-BiLLT]). The language tracts were visualized in all control children and in four CP patients. In one CP patient without any objective language comprehension skills, no language tract could be visualized. Both language and pyramidal tracts were smaller in patients than in controls. These preliminary data indicate a relation between language tracts and language skills. Further research is necessary to study the value of structural integrity of language tracts in predicting language comprehension in CP patients.

Damage to ventral and dorsal language pathways in acute aphasia

Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the ventral extreme capsule pathway.

Fiber pathways connecting cortical areas relevant for spatial orienting and exploration

By implementing a task that closely resembled a clinical test for diagnosing spatial neglect in stroke patients, Himmelbach et al. (: Neuroimage 32:1747-1759) found significantly increased activation during active exploration in those cortical areas in healthy subjects that are known to induce spatial neglect in case of a lesion. The present study investigated whether direct intra-hemispheric cortico-cortical connections could be found between these activated clusters using a probabilistic fiber-tracking approach in 52 healthy subjects. We found that parts of the extreme capsule (EmC) and the middle longitudinal fascicle (MdLF) connected the functional cluster in the prefrontal cortex with the superior temporal cortex and the temporo-parietal junction (TPJ) area in both hemispheres. The activation peak in the TPJ was additionally connected to the inferior frontal cortex by parts of the arcuate fascicle and the superior longitudinal fascicle (SLF II) in the right hemisphere. Our study elucidates the connections constituting the perisylvian network for spatial orienting and attention. Hence, we complement the knowledge from patients suffering from spatial neglect by giving first empirical evidence for the complete postulated network in healthy subjects.

Speech entrainment enables patients with Broca's aphasia to produce fluent speech.

A distinguishing feature of Broca's aphasia is non-fluent halting speech typically involving one to three words per utterance. Yet, despite such profound impairments, some patients can mimic audio-visual speech stimuli enabling them to produce fluent speech in real time. We call this effect 'speech entrainment' and reveal its neural mechanism as well as explore its usefulness as a treatment for speech production in Broca's aphasia. In Experiment 1, 13 patients with Broca's aphasia were tested in three conditions: (i) speech entrainment with audio-visual feedback where they attempted to mimic a speaker whose mouth was seen on an iPod screen; (ii) speech entrainment with audio-only feedback where patients mimicked heard speech; and (iii) spontaneous speech where patients spoke freely about assigned topics. The patients produced a greater variety of words using audio-visual feedback compared with audio-only feedback and spontaneous speech. No difference was found between audio-only feedback and spontaneous speech. In Experiment 2, 10 of the 13 patients included in Experiment 1 and 20 control subjects underwent functional magnetic resonance imaging to determine the neural mechanism that supports speech entrainment. Group results with patients and controls revealed greater bilateral cortical activation for speech produced during speech entrainment compared with spontaneous speech at the junction of the anterior insula and Brodmann area 47, in Brodmann area 37, and unilaterally in the left middle temporal gyrus and the dorsal portion of Broca's area. Probabilistic white matter tracts constructed for these regions in the normal subjects revealed a structural network connected via the corpus callosum and ventral fibres through the extreme capsule. Unilateral areas were connected via the arcuate fasciculus. In Experiment 3, all patients included in Experiment 1 participated in a 6-week treatment phase using speech entrainment to improve speech production. Behavioural and functional magnetic resonance imaging data were collected before and after the treatment phase. Patients were able to produce a greater variety of words with and without speech entrainment at 1 and 6 weeks after training. Treatment-related decrease in cortical activation associated with speech entrainment was found in areas of the left posterior-inferior parietal lobe. We conclude that speech entrainment allows patients with Broca's aphasia to double their speech output compared with spontaneous speech. Neuroimaging results suggest that speech entrainment allows patients to produce fluent speech by providing an external gating mechanism that yokes a ventral language network that encodes conceptual aspects of speech. Preliminary results suggest that training with speech entrainment improves speech production in Broca's aphasia providing a potential therapeutic method for a disorder that has been shown to be particularly resistant to treatment.

Beyond the arcuate fasciculus: consensus and controversy in the connectional anatomy of language

The growing consensus that language is distributed into large-scale cortical and subcortical networks has brought with it an increasing focus on the connectional anatomy of language, or how particular fibre pathways connect regions within the language network. Understanding connectivity of the language network could provide critical insights into function, but recent investigations using a variety of methodologies in both humans and non-human primates have provided conflicting accounts of pathways central to language. Some of the pathways classically considered language pathways, such as the arcuate fasciculus, are now argued to be domain-general rather than specialized, which represents a radical shift in perspective. Other pathways described in the non-human primate remain to be verified in humans. In this review, we examine the consensus and controversy in the study of fibre pathway connectivity for language. We focus on seven fibre pathways-the superior longitudinal fasciculus and arcuate fasciculus, the uncinate fasciculus, extreme capsule, middle longitudinal fasciculus, inferior longitudinal fasciculus and inferior fronto-occipital fasciculus-that have been proposed to support language in the human. We examine the methods in humans and non-human primate used to investigate the connectivity of these pathways, the historical context leading to the most current understanding of their anatomy, and the functional and clinical correlates of each pathway with reference to language. We conclude with a challenge for researchers and clinicians to establish a coherent framework within which fibre pathway connectivity can be systematically incorporated to the study of language.

Topography of Gng2- and NetrinG2-Expression Suggests an Insular Origin of the Human Claustrum

The claustrum has been described in the forebrain of all mammals studied so far. It has been suggested that the claustrum plays a role in the integration of multisensory information: however, its detailed structure and function remain enigmatic. The human claustrum is a thin, irregular, sheet of grey matter located between the inner surface of the insular cortex and the outer surface of the putamen. Recently, the G-protein gamma2 subunit (Gng2) was proposed as a specific claustrum marker in the rat, and used to better delineate its anatomical boundaries and connections. Additional claustral markers proposed in mammals include Netrin-G2 in the monkey and latexin in the cat. Here we report the expression and distribution of Gng2 and Netrin-G2 in human post-mortem samples of the claustrum and adjacent structures. Gng2 immunoreactivity was detected in the neuropil of the claustrum and of the insular cortex but not in the putamen. A faint labelling was present also in the external and extreme capsules. Double-labelling experiments indicate that Gng2 is also expressed in glial cells. Netrin-G2 labelling was seen in neuronal cell bodies throughout the claustrum and the insular cortex but not in the medially adjacent putamen. No latexin immunoreactive element was detected in the claustrum or adjacent structures. Our results confirm that both the Gng2 and the Netrin-G2 proteins show an affinity to the claustrum and related formations also in the human brain. The presence of Gng2 and Netrin-G2 immunoreactive elements in the insular cortex, but not in the putamen, suggests a possible common ontogeny of the claustrum and insula.

The study of the microsurgical anatomy on the relationship of the claustrum with its adjacent white matter fiber tracts

Objective The goal in this study is to investigate the microsurgical anatomy of the relationship of the claustrum with its adjacent white matter fiber tracts,and to analyze the functional implications of the findings.Methods Ten formalin - fixed human brain hemispheres were dissected using the Klingler fiber dissection technique,with the aid of an operating microscope at 4 ～25 magnification.The microsurgical anatomy of the relationship of the claustrnm with its adjacent white matter fiber tracts was observed.Results Macroscopically,we divide the claustrum into 2 parts:the dorsal claustrum and the ventral claustrum,which in humans the dorsal claustrum was posterosuperior,and the ventral claustrum was anteroinferior.The claustrum was a thin,irregular sheet of grey matter which was surrounded by several adjacent white na tter fiber tracts. The extreme capsule,external capsule,uncinate fascicle,inferior occipitofrontal fascicle were located respectively lateral,dorsal and medial,ventral to the claustrum,and the sublenticular portion of the internal capsule which runed from medial to Iateral was located posteroinferior tothe claustrum. Although the fibers from the uncinate and inferior occipitofrontal fascicles traverse and fragment the ventral claustrum,the fibers from the extreme capsule and the external capsule initiated from or terminated to the dorsal claustrum,and part of the fibers from the internal capsule traverse the posteroinferior pole of the elaustrum.The ventral claustrum was related closely with several grey matter nucleus of basilad telencephalon such as the amygdala,nucleus accumbens and substantia innominata. Conclusion The study of anatomy and function of the adjacent white matter fiber tracts of the claustrum may provide a new approach for the function of the claustrum. Key words: Claustrum; White matter fiber tracts; Insula; Network

Fiber anatomy of dorsal and ventral language streams

Recent advances in neuroimaging have led to new insights into the organization of language related networks. Increasing evidence supports the model of dorsal and ventral streams of information flow between language-related areas. Therefore, a review of the descriptions of language-related fiber anatomy in the human and monkey brain was performed. In addition, case studies of macroscopical fiber dissection and polarized light imaging (PLI) with special focus on the ventral stream were done. Several fiber structures can be identified to play a role in language, i.e. the arcuate fasciculus as a part of the superior longitudinal fasciculus, the middle longitudinal fasciculus, the inferior fronto-occipital fasciculus, and extreme and external capsules. Substantial differences between human and monkey fiber architecture have been identified. Despite inconsistencies based on different terminologies used, there can be no doubt that dorsal and ventral language streams have a clear correlation in the structure of white matter tracts.

Age-dependent structural connectivity effects in fragile x premutation.

To examine the effects of premutation alleles on major brain fiber tracts in males. Cross-sectional study performed in 2007-2009. Institutional practice. Fifteen younger (18-45 years old) carriers, 11 older (>45 years old) unaffected carriers, and 15 older carriers with fragile X-associated tremor/ataxia syndrome, together with 19 younger and 15 older controls matched by age and educational level. Diffusion tensor imaging was performed on all study participants. Eleven fiber tracts important for motor, social, emotional, and cognitive functions were reconstructed and quantified. Complementary tract-based spatial statistical analyses were performed in core white matter. In the younger carriers, premutation status was associated with a greater age-related connectivity decline in the extreme capsule. Among older carriers, unaffected individuals did not display structural alterations, whereas the affected carriers showed connectivity loss in 5 fiber tracts and exhibited greater age-related connectivity decline in all 11 tracts compared with the controls. In addition, 9 fiber tracts showed significantly higher variability relative to the controls, and symptom severity explained the variability in 6 measurements from the superior cerebellar peduncle, corpus callosum, and cingulum. The findings revealed widespread alterations in structural connectivity associated with fragile X-associated tremor/ataxia syndrome and preserved or subtle changes in structural connectivity in unaffected carriers. Diffusion tensor imaging is sensitive to pathologic changes in the white matter associated with this neurodegenerative disorder. Wang et al examine the effects of premutation alleles on major brain fiber tracts in males, who are at risk of developing fragile X-associated tremor/ataxia syndrome and may manifest subtle cognitive, social, and emotional disturbances before clinical involvement.

Functional Organization of the Neural Language System: Dorsal and Ventral Pathways Are Critical for Syntax

The core of human language, which differentiates it from the communicative abilities of other species, is the set of combinatorial operations called syntax. For over a century researchers have attempted to understand how this essential function is organized in the brain. Here, we combine behavioral and neuroimaging methods, with left hemisphere-damaged patients and healthy controls, to identify the pathways connecting the brain regions involved in syntactic processing. In a previous functional magnetic resonance imaging study (Tyler LK, Wright P, Randall B, Marslen-Wilson WD, Stamatakis EA. 2010b. Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function? Brain. 133(11):3396-3408.), we established that regions of left inferior frontal cortex and left posterior middle temporal cortex were activated during syntactic processing. These clusters were used here as seeds for probabilistic tractography analyses in patients and controls, allowing us to delineate, and measure the integrity of, the white matter tracts connecting the frontal and temporal regions active for syntax. We found that structural disconnection in either of 2 fiber bundles--the arcuate fasciculus or the extreme capsule fiber system--was associated with syntactic impairment in patients. The results demonstrate the causal role in syntactic analysis of these 2 major left hemisphere fiber bundles--challenging existing views about their role in language functions and providing a new basis for future research in this key area of human cognition.

Continuity, Divergence, and the Evolution of Brain Language Pathways

Recently, the assumption of evolutionary continuity between humans and non-human primates has been used to bolster the hypothesis that human language is mediated especially by the ventral extreme capsule pathway that mediates auditory object recognition in macaques. Here, we argue for the importance of evolutionary divergence in understanding brain language evolution. We present new comparative data reinforcing our previous conclusion that the dorsal arcuate fasciculus pathway was more significantly modified than the ventral extreme capsule pathway in human evolution. Twenty-six adult human and twenty-six adult chimpanzees were imaged with diffusion-weighted MRI and probabilistic tractography was used to track and compare the dorsal and ventral language pathways. Based on these and other data, we argue that the arcuate fasciculus is likely to be the pathway most essential for higher-order aspects of human language such as syntax and lexical–semantics.

Dynamic Processing in the Human Language System: Synergy between the Arcuate Fascicle and Extreme Capsule

The production and comprehension of human language is thought to involve a network of frontal, parietal, and temporal cortical loci interconnected by two dominant white matter pathways. These two white matter bundles, often referred to as the dorsal and ventral processing tracts, are hypothesized to have markedly different language functions. The dorsal tract is thought to process phonological processing, while the ventral tract is considered to abet semantics. This proposed functional differentiation of tracts is similar to the ventral and dorsal dichotomy proposed for the visual and auditory systems. The present study evaluated this characterization of the language system in the context of various components involved in its function. Twenty-four chronic stroke patients completed a battery of 10 language tests designed to measure performance on the comprehension and production of phonology, morphology, semantics, and syntax. The patients also completed diffusion MRI scanning. Lesions were confined to the left hemisphere, but the size and location of the insult varied so that patients had damage to a single tract, both tracts, or neither tract. Individual FA maps were generated, and focal areas of hypointensity served as markers of white matter damage. Whole-brain voxel-by-voxel correlations revealed that only phonological and semantic tasks fit into the dual-stream model, while syntax and morphology involved both pathways. ROI analyses of the arcuate fascicle and extreme capsule supported this finding. These data suggest that natural language function is more likely to reflect a synergistic system rather than a segregated dual-stream system.

Syntactic Processing Depends on Dorsal Language Tracts

Frontal and temporal language areas involved in syntactic processing are connected by several dorsal and ventral tracts, but the functional roles of the different tracts are not well understood. To identify which white matter tract(s) are important for syntactic processing, we examined the relationship between white matter damage and syntactic deficits in patients with primary progressive aphasia, using multimodal neuroimaging and neurolinguistic assessment. Diffusion tensor imaging showed that microstructural damage to left hemisphere dorsal tracts--the superior longitudinal fasciculus including its arcuate component--was strongly associated with deficits in comprehension and production of syntax. Damage to these dorsal tracts predicted syntactic deficits after gray matter atrophy was taken into account, and fMRI confirmed that these tracts connect regions modulated by syntactic processing. In contrast, damage to ventral tracts--the extreme capsule fiber system or the uncinate fasciculus--was not associated with syntactic deficits. Our findings show that syntactic processing depends primarily on dorsal language tracts.

Neural plasticity after pre-linguistic injury to the arcuate and superior longitudinal fasciculi

We describe the case of girl who was born prematurely and diagnosed periventricular leukomalacia, a condition characterized by severe injury to the white matter tracts primarily surrounding the ventricles. At 12 years of age, we obtained diffusion tensor imaging (DTI) data on this child as part of a research protocol. Multiple analyses of DTI data, including tractography, showed that the left and right arcuate and superior longitudinal fasciculi were missing in the child though all other major white matter tracts were present. Standardized psychometric tests at age 12 years revealed that despite early language delays, she had average scores on expressive language, sentence repetition, and reading, functions that have been hypothesized to depend on signals carried by the arcuate fasciculus. We identified intact ventral connections between the temporal and frontal lobes through the extreme capsule fiber system and uncinate fasciculus. Preserved language and reading function after serious injury to the arcuate fasciculus highlights the plasticity of the developing brain after severe white matter injury early in life.

Impairment of Speech Production Predicted by Lesion Load of the Left Arcuate Fasciculus

Previous studies have suggested that patients' potential for poststroke language recovery is related to lesion size; however, lesion location may also be of importance, particularly when fiber tracts that are critical to the sensorimotor mapping of sounds for articulation (eg, the arcuate fasciculus) have been damaged. In this study, we tested the hypothesis that lesion loads of the arcuate fasciculus (ie, volume of arcuate fasciculus that is affected by a patient's lesion) and of 2 other tracts involved in language processing (the extreme capsule and the uncinate fasciculus) are inversely related to the severity of speech production impairments in patients with stroke with aphasia. Thirty patients with chronic stroke with residual impairments in speech production underwent high-resolution anatomic MRI and a battery of cognitive and language tests. Impairment was assessed using 3 functional measures of spontaneous speech (eg, rate, informativeness, and overall efficiency) as well as naming ability. To quantitatively analyze the relationship between impairment scores and lesion load along the 3 fiber tracts, we calculated tract-lesion overlap volumes for each patient using probabilistic maps of the tracts derived from diffusion tensor images of 10 age-matched healthy subjects. Regression analyses showed that arcuate fasciculus lesion load, but not extreme capsule or uncinate fasciculus lesion load or overall lesion size, significantly predicted rate, informativeness, and overall efficiency of speech as well as naming ability. A new variable, arcuate fasciculus lesion load, complements established voxel-based lesion mapping techniques and, in the future, may potentially be used to estimate impairment and recovery potential after stroke and refine inclusion criteria for experimental rehabilitation programs.