Lesion localization of speech comprehension deficits in chronic aphasia

Objective: Voxel-based lesion-symptom mapping (VLSM) was used to localize impairments specific to multiword (phrase and sentence) spoken language comprehension.

Methods: Participants were 51 right-handed patients with chronic left hemisphere stroke. They performed an auditory description naming (ADN) task requiring comprehension of a verbal description, an auditory sentence comprehension (ASC) task, and a picture naming (PN) task. Lesions were mapped using high-resolution MRI. VLSM analyses identified the lesion correlates of ADN and ASC impairment, first with no control measures, then adding PN impairment as a covariate to control for cognitive and language processes not specific to spoken language.

Results: ADN and ASC deficits were associated with lesions in a distributed frontal-temporal parietal language network. When PN impairment was included as a covariate, both ADN and ASC deficits were specifically correlated with damage localized to the mid-to-posterior portion of the middle temporal gyrus (MTG).

Conclusions: Damage to the mid-to-posterior MTG is associated with an inability to integrate multiword utterances during comprehension of spoken language. Impairment of this integration process likely underlies the speech comprehension deficits characteristic of Wernicke aphasia.

Pillay SB, Binder JR, Humphries CJ, Gross WL, Book, DS (2017) Lesion localization of speech comprehension deficits in chronic aphasia. Neurology; doi: 10.1212/WNL.0000000000003683

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Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness


Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1 Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

Liu, X, Lauer, KK, Ward, BD, Roberts, C, Liu, S, Gollapudy, S, Rohloff, R, Gross, WL, Chen, G, Xu, Z, Binder, JR, Li, SJ, Hudetz, AG (2016) Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness. Neuroimage; doi:10.1016/j.neuroimage.2016.12.043

High-resolution parcellation of brain connectivity improves differentiation of states of consciousness during graded propofol sedation

Liu, X, Lauer, KK, Ward, BD, Roberts, C, Liu, S, Gollapudy, S, Rohloff, R, Gross, WL, Chen, G, Binder, JR, Li, SJ, Hudetz, AJ (2016) High-resolution parcellation of brain connectivity improves differentiation of states of consciousness during graded propofol sedation. Brain Connectivity. In review

Surface errors without semantic impairment in acquired dyslexia: a voxel-based lesion–symptom mapping study


Patients with surface dyslexia have disproportionate difficulty pronouncing irregularly spelled words (e.g. pint), suggesting im- paired use of lexical-semantic information to mediate phonological retrieval. Patients with this deficit also make characteristic ‘regularization’ errors, in which an irregularly spelled word is mispronounced by incorrect application of regular spelling-sound correspondences (e.g. reading plaid as ‘played’), indicating over-reliance on sublexical grapheme–phoneme correspondences. We examined the neuroanatomical correlates of this specific error type in 45 patients with left hemisphere chronic stroke. Voxel-based lesion–symptom mapping showed a strong positive relationship between the rate of regularization errors and damage to the posterior half of the left middle temporal gyrus. Semantic deficits on tests of single-word comprehension were generally mild, and these deficits were not correlated with the rate of regularization errors. Furthermore, the deep occipital-temporal white matter locus associated with these mild semantic deficits was distinct from the lesion site associated with regularization errors. Thus, in contrast to patients with surface dyslexia and semantic impairment from anterior temporal lobe degeneration, surface errors in our patients were not related to a semantic deficit. We propose that these patients have an inability to link intact semantic represen- tations with phonological representations. The data provide novel evidence for a post-semantic mechanism mediating the produc- tion of surface errors, and suggest that the posterior middle temporal gyrus may compute an intermediate representation linking semantics with phonology.

Binder, JR, Pillay, SB, Humphries, CJ, Gross, WL, Graves, WW, Book, DS (2016) Surface errors without semantic impairment in acquired dyslexia: a voxel-based lesion–symptom mapping study. Brain; doi:10.1093/brain/aww029

Predicting brain activation patterns associated with individual lexical concepts based on five sensory-motor attributes


While major advances have been made in uncovering the neural processes underlying perceptual representations, our grasp of how the brain gives rise to conceptual knowledge remains relatively poor. Recent work has provided strong evidence that concepts rely, at least in part, on the same sensory and motor neural systems through which they were acquired, but it is still unclear whether the neural code for concept representation uses information about sensory-motor features to discriminate between concepts. In the present study, we investigate this question by asking whether an encoding model based on five semantic attributes directly related to sensory-motor experience – sound, color, visual motion, shape, and manipulation – can successfully predict patterns of brain activation elicited by individual lexical concepts. We collected ratings on the relevance of these five attributes to the meaning of 820 words, and used these ratings as predictors in a multiple regression model of the fMRI signal associated with the words in a separate group of participants. The five resulting activation maps were then combined by linear summation to predict the distributed activation pattern elicited by a novel set of 80 test words. The encoding model predicted the activation patterns elicited by the test words significantly better than chance. As expected, prediction was successful for concrete but not for abstract concepts. Comparisons between encoding models based on different combinations of attributes indicate that all five attributes contribute to the representation of concrete concepts. Consistent with embodied theories of semantics, these results show, for the first time, that the distributed activation pattern associated with a concept combines information about different sensory-motor attributes according to their respective relevance. Future research should investigate how additional features of phenomenal experience contribute to the neural representation of conceptual knowledge.

Fernandino, L, Humphries, CJ, Seidenberg, MS, Gross, WL, Conant LL, Binder, JR (2015) Predicting brain activation patterns associated with individual lexical concepts based on five sensory-motor attributes. Neuropsychologia; doi:10.1016/j.neuropsychologia.2015.04.009

Concept Representation Reflects Multimodal Abstraction: A Framework for Embodied Semantics


Recent research indicates that sensory and motor cortical areas play a significant role in the neural representation of concepts. However, little is known about the overall architecture of this representational system, including the role played by higher level areas that integrate different types of sensory and motor information. The present study addressed this issue by investigating the simultaneous contributions of multiple sensory-motor modalities to semantic word processing. With a multivariate fMRI design, we examined activation associated with 5 sensory-motor attributes—color, shape, visual motion, sound, and manipulation—for 900 words. Regions responsive to each attribute were identified using independent ratings of the attributes’ relevance to the meaning of each word. The results indicate that these aspects of conceptual knowledge are encoded in multimodal and higher level unimodal areas involved in processing the corresponding types of information during perception and action, in agreement with embodied theories of semantics. They also reveal a hierarchical system of abstracted sensory-motor representations incorporating a major division between object interaction and object perception processes.

Fernandino, L, Binder, JR, Desai, RH, Pendl, SL, Humphries, CJ, Gross, WL, Conant, LL, Seidenberg, MS (2015) Concept Representation Reflects Multimodal Abstraction: A Framework for Embodied Semantics. Cerebral Cortex; doi: 10.1093/cercor/bhv020

Alternative Thresholding Methods for FMRI Data Optimized for Surgical Planning


Current methods for thresholding functional magnetic resonance imaging (fMRI) maps are based on the well-known hypothesis-test framework, optimal for addressing novel theoretical claims. However, these methods as typically practiced have a strong bias toward protecting the null hypothesis, and thus may not provide an optimal balance between specificity and sensitivity in forming activation maps for surgical planning. Maps based on hypothesis-test thresholds are also highly sensitive to sample size and signal-to-noise ratio, whereas many clinical applications require methods that are robust to these effects. We propose a new thresholding method, optimized for surgical planning, based on normalized amplitude thresholding. We show that this method produces activation maps that are more reproducible and more predictive of postoperative cognitive outcome than maps produced with current standard thresholding methods.

Gross, W. L., & Binder, J. R. (2014). Alternative thresholding methods for fMRI data optimized for surgical planning. NeuroImage, 84C, 554–561. doi:10.1016/j.neuroimage.2013.08.066

Psychosis in the Context of Sodium Oxybate Therapy


Sodium oxybate (brand name Xyrem) is a sodium salt of gam- ma-hydroxybutyric acid (GHB), an endogenous CNS depres- sant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and with- drawal. However, there are no reports of these effects when us- ing clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication. It is important for prescribers of sodium oxybate to be aware of the possibility of significant psychiatric side effects of this medi- cation, as well as withdrawal symptoms, even at clinical doses. Keywords: Sodium oxybate, narcolepsy, psychoses – substance- induced, substance withdrawal syndrome

Langford, J., & Gross, W. L. (2011). Psychosis in the context of sodium oxybate therapy. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 7(6), 665–666. doi:10.5664/jcsm.1478

Mapping anterior temporal lobe language areas with fMRI: A multicenter normative study


Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story N Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story–Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

Binder JR, Gross WL, Allendorfer JB, Bonilha L, Chapin J, Edwards JC, Grabowski TJ, Langfitt JT, Loring DW, Lowe MJ, Koenig K, Morgan PS, Ojemann JG, Rorden C, Szaflarski JP, Tivarus ME, Weaver KE. (2011). Mapping anterior temporal lobe language areas with fMRI: a multicenter normative study. Neuroimage, 15;54(2), 1465-1475.

PhD dissertation: Using fMRI to Improve Outcome in the Surgical Treatment of Temporal Lobe Epilepsy


Temporal lobe epilepsy is a neurological disease that affects millions worldwide, and can be effectively treated through surgical resection of portions of the anterior temporal lobe (ATL). Though effective for seizure control, this surgery occasionally produces language and verbal memory deficits. The goal of this work was to improve language-mapping techniques using fMRI in order to better inform the surgeon prior to ATL resection.

This was approached in three main experiments. First, an ATL deactivation task was developed. Since the ATL is hypothesized to be involved in semantic memory processing, mathematical stimuli were used, which are strongly attentionally engaging, but do not contain much semantic content. This was compared to previously used tasks and shown to be superior at producing ATL deactivation.

Second, an activation task was designed using story passages, differing from many previous studies that have used single word stimuli to activate the ATL. This task was combined with the math baseline task to produce maximal contrast in the ATL.

Finally, an improved thresholding method is proposed that increases the consistency of fMRI maps in individual patients, adapted for the requirements of surgical planning. While traditional methods of thresholding are effective for research questions, use of activation maps for surgical planning requires an approach that is less sensitive to individual variability in noise level. This new method was shown to be superior to current methods at predicting patient outcome.