Stephen M. Wilson

Voxel-based lesion–symptom mapping

For more than a century, lesion–symptom mapping studies have yielded valuable insights into the relationships between brain and behavior, but newer imaging techniques have surpassed lesion analysis in examining functional networks. Here we used a new method—voxel-based lesion–symptom mapping (VLSM)—to analyze the relationship between tissue damage and behavior on a voxel-by-voxel basis, as in functional neuroimaging. We applied VLSM to measures of speech fluency and language comprehension in 101 left-hemisphere-damaged aphasic patients: the VLSM maps for these measures confirm the anticipated contrast between anterior and posterior areas, and they also indicate that interacting regions facilitate fluency and auditory comprehension, in agreement with findings from modern brain imaging.

Congruent Embodied Representations for Visually Presented Actions and Linguistic Phrases Describing Actions

The thesis of embodied semantics holds that conceptual representations accessed during linguistic processing are, in part, equivalent to the sensory-motor representations required for the enactment of the concepts described . Here, using fMRI, we tested the hypothesis that areas in human premotor cortex that respond both to the execution and observation of actions-mirror neuron areas -are key neural structures in these processes. Participants observed actions and read phrases relating to foot, hand, or mouth actions. In the premotor cortex of the left hemisphere, a clear congruence was found between effector-specific activations of visually presented actions and of actions described by literal phrases. These results suggest a key role of mirror neuron areas in the re-enactment of sensory-motor representations during conceptual processing of actions invoked by linguistic stimuli.

Clinicopathological correlations in corticobasal degeneration.

To characterize cognitive and behavioral features, physical findings, and brain atrophy patterns in pathology‐proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with known histopathology.

Left hemisphere motor facilitation in response to manual action sounds

Previous studies indicate that the motor areas of both hemispheres are active when observing actions. Here we explored how the motor areas of each hemisphere respond to the sounds associated with actions. We used transcranial magnetic stimulation (TMS) to measure motor corticospinal excitability of hand muscles while listening to sounds. Sounds associated with bimanual actions produced greater motor corticospinal excitability than sounds associated with leg movements or control sounds. This facilitation was exclusively lateralized to the left hemisphere, the dominant hemisphere for language. These results are consistent with the hypothesis that action coding may be a precursor of language.

Language networks in semantic dementia

Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls. The left uncinate fasciculus and the genu and splenium of the corpus callosum were also obtained for comparison with previous studies. From each tract, mean diffusivity, fractional anisotropy, as well as parallel and transverse diffusivities were obtained. Diffusion tensor imaging results were related to grey and white matter atrophy volume assessed by voxel-based morphometry and functional magnetic resonance imaging activations during a reading task. Semantic dementia patients had significantly higher mean diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The arcuate and uncinate fasciculi demonstrated significantly higher mean diffusivity, parallel and transverse and significantly lower fractional anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively spared, with a significant difference observed for transverse diffusivity and fractional anisotropy, only. In the corpus callosum, the genu showed lower fractional anisotropy compared with controls, while no difference was found in the splenium. The left parietal cortex did not show significant volume changes on voxel-based morphometry and demonstrated normal functional magnetic resonance imaging activation in response to reading items that stress sublexical phonological processing. This study shows that semantic dementia is associated with anatomical damage to the major superior and inferior temporal white matter connections of the left hemisphere likely involved in semantic and lexical processes, with relative sparing of the fronto-parietal superior longitudinal fasciculus. Fronto-parietal regions connected by this tract were activated normally in the same patients during sublexical reading. These findings contribute to our understanding of the anatomical changes that occur in semantic dementia, and may further help to explain the dissociation between marked single-word and object knowledge deficits, but sparing of phonology and fluency in semantic dementia.

Detecting sarcasm from paralinguistic cues: Anatomic and cognitive correlates in neurodegenerative disease

While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic dementia [SemD], 4 progressive non-fluent aphasia, 27 Alzheimers disease, 6 corticobasal degeneration, 9 progressive supranuclear palsy, 13 healthy older controls) were tested using the Social Inference - Minimal subtest of The Awareness of Social Inference Test (TASIT). Subjects watched brief videos depicting sincere or sarcastic communication and answered yes-no questions about the speakers intended meaning. All groups interpreted Sincere (SIN) items normally, and only the SemD group was impaired on the Simple Sarcasm (SSR) condition. Patients failing the SSR performed more poorly on dynamic emotion recognition tasks and had more neuropsychiatric disturbances, but had better verbal and visuospatial working memory than patients who comprehended sarcasm. Voxel-based morphometry analysis of SSR scores in SPM5 demonstrated that poorer sarcasm comprehension was predicted by smaller volume in bilateral posterior parahippocampi (PHc), temporal poles, and R medial frontal pole (pFWE<0.05). This study provides lesion data suggesting that the PHc may be involved in recognizing a paralinguistic speech profile as abnormal, leading to interpretive processing by the temporal poles and right medial frontal pole that identifies the social context as sarcastic, and recognizes the speakers paradoxical intentions.

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 basis of interpersonal traits in neurodegenerative diseases

Several functional and structural imaging studies have investigated the neural basis of personality in healthy adults, but human lesions studies are scarce. Personality changes are a common symptom in patients with neurodegenerative diseases like frontotemporal dementia (FTD) and semantic dementia (SD), allowing a unique window into the neural basis of personality. In this study, we used the Interpersonal Adjective Scales to investigate the structural basis of eight interpersonal traits (dominance, arrogance, coldness, introversion, submissiveness, ingenuousness, warmth, and extraversion) in 257 subjects: 214 patients with neurodegenerative diseases such as FTD, SD, progressive nonfluent aphasia, Alzheimers disease, amnestic mild cognitive impairment, corticobasal degeneration, and progressive supranuclear palsy and 43 healthy elderly people. Measures of interpersonal traits were correlated with regional atrophy pattern using voxel-based morphometry (VBM) analysis of structural MR images. Interpersonal traits mapped onto distinct brain regions depending on the degree to which they involved agency and affiliation. Interpersonal traits high in agency related to left dorsolateral prefrontal and left lateral frontopolar regions, whereas interpersonal traits high in affiliation related to right ventromedial prefrontal and right anteromedial temporal regions. Consistent with the existing literature on neural networks underlying social cognition, these results indicate that brain regions related to externally focused, executive control-related processes underlie agentic interpersonal traits such as dominance, whereas brain regions related to internally focused, emotion- and reward-related processes underlie affiliative interpersonal traits such as warmth. In addition, these findings indicate that interpersonal traits are subserved by complex neural networks rather than discrete anatomic areas.

Giving speech a hand: Gesture modulates activity in auditory cortex during speech perception

Viewing hand gestures during face‐to‐face communication affects speech perception and comprehension. Despite the visible role played by gesture in social interactions, relatively little is known about how the brain integrates hand gestures with co‐occurring speech. Here we used functional magnetic resonance imaging (fMRI) and an ecologically valid paradigm to investigate how beat gesture—a fundamental type of hand gesture that marks speech prosody—might impact speech perception at the neural level. Subjects underwent fMRI while listening to spontaneously‐produced speech accompanied by beat gesture, nonsense hand movement, or a still body; as additional control conditions, subjects also viewed beat gesture, nonsense hand movement, or a still body all presented without speech. Validating behavioral evidence that gesture affects speech perception, bilateral nonprimary auditory cortex showed greater activity when speech was accompanied by beat gesture than when speech was presented alone. Further, the left superior temporal gyrus/sulcus showed stronger activity when speech was accompanied by beat gesture than when speech was accompanied by nonsense hand movement. Finally, the right planum temporale was identified as a putative multisensory integration site for beat gesture and speech (i.e., here activity in response to speech accompanied by beat gesture was greater than the summed responses to speech alone and beat gesture alone), indicating that this area may be pivotally involved in synthesizing the rhythmic aspects of both speech and gesture. Taken together, these findings suggest a common neural substrate for processing speech and gesture, likely reflecting their joint communicative role in social interactions. Hum Brain Mapp, 2009.

Neural Correlates of Syntactic Processing in the Nonfluent Variant of Primary Progressive Aphasia

The left posterior inferior frontal cortex (IFC) is important for syntactic processing, and has been shown in many functional imaging studies to be differentially recruited for the processing of syntactically complex sentences relative to simpler ones. In the nonfluent variant of primary progressive aphasia (PPA), degeneration of the posterior IFC is associated with expressive and receptive agrammatism; however, the functional status of this region in nonfluent PPA is not well understood. Our objective was to determine whether the atrophic posterior IFC is differentially recruited for the processing of syntactically complex sentences in nonfluent PPA. Using structural and functional magnetic resonance imaging, we quantified tissue volumes and functional responses to a syntactic comprehension task in eight patients with nonfluent PPA, compared to healthy age-matched controls. In controls, the posterior IFC showed more activity for syntactically complex sentences than simpler ones, as expected. In nonfluent PPA patients, the posterior IFC was atrophic and, unlike controls, showed an equivalent level of functional activity for syntactically complex and simpler sentences. This abnormal pattern of functional activity was specific to the posterior IFC: the mid-superior temporal sulcus, another region modulated by syntactic complexity in controls, showed normal modulation by complexity in patients. A more anterior inferior frontal region was recruited by patients, but did not support successful syntactic processing. We conclude that in nonfluent PPA, the posterior IFC is not only structurally damaged, but also functionally abnormal, suggesting a critical role for this region in the breakdown of syntactic processing in this syndrome.