Juliana V. Baldo

COGNITIVE PROCESSING SPEED AND THE STRUCTURE OF WHITE MATTER PATHWAYS: CONVERGENT EVIDENCE FROM NORMAL VARIATION AND LESION STUDIES

We investigated the relation between cognitive processing speed and structural properties of white matter pathways via convergent imaging studies in healthy and brain-injured groups. Voxel-based morphometry (VBM) was applied to diffusion tensor imaging data from thirty-nine young healthy subjects in order to investigate the relation between processing speed, as assessed with the Digit-Symbol subtest from WAIS-III, and fractional anisotropy, an index of microstructural organization of white matter. Digit-Symbol performance was positively correlated with fractional anisotropy of white matter in the parietal and temporal lobes bilaterally and in the left middle frontal gyrus. Fiber tractography indicated that these regions are consistent with the trajectories of the superior and inferior longitudinal fasciculi. In a second investigation, we assessed the effect of white matter damage on processing speed using voxel-based lesion-symptom mapping (VLSM) analysis of data from seventy-two patients with left-hemisphere strokes. Lesions in left parietal white matter, together with cortical lesions in supramarginal and angular gyri were associated with impaired performance. These findings suggest that cognitive processing speed, as assessed by the Digit-Symbol test, is closely related to the structural integrity of white matter tracts associated with parietal and temporal cortices and left middle frontal gyrus. Further, fiber tractography applied to VBM results and the patient findings suggest that the superior longitudinal fasciculus, a major tract subserving fronto-parietal integration, makes a prominent contribution to processing speed.

Role of frontal versus temporal cortex in verbal fluency as revealed by voxel-based lesion symptom mapping

Category and letter fluency tasks have been used to demonstrate psychological and neurological dissociations between semantic and phonological aspects of word retrieval. Some previous neuroimaging and lesion studies have suggested that category fluency (semantic-based word retrieval) is mediated primarily by temporal cortex, while letter fluency (letter-based word retrieval) is mediated primarily by frontal cortex. Other studies have suggested that both letter and category fluency are mediated by frontal cortex. We tested these hypotheses using voxel-based lesion symptom mapping (VLSM) in a group of 48 left-hemisphere stroke patients. VLSM maps revealed that category and letter fluency deficits correlate with lesions in temporal and frontal cortices, respectively. Other regions, including parietal cortex, were significantly implicated in both tasks. Our findings are therefore consistent with the hypothesis that temporal cortex subserves word retrieval constrained by semantics, whereas frontal regions are more critical for strategic word retrieval constrained by phonology.

Letter and category fluency in patients with frontal lobe lesions.

This study examines the hypothesis that patients with frontal lobe lesions are impaired on tests of letter but not category fluency. This hypothesis was proposed by Moscovitch (1994), based on a series of cognitive studies with young, normal participants. A group of patients with lateral prefrontal lesions and age-matched controls were tested on 2 tests of verbal fluency, the FAS task and a category fluency task that used semantic categories as cues (e.g., animals). Patients with frontal lobe lesions generated fewer items than controls on both letter and category fluency. This effect did not interact with the type of fluency test, suggesting that the frontal lobes are more generally involved in verbal fluency. Moreover, this pattern of findings, along with previous results of impaired free recall and remote retrieval in this patient group, suggests that patients with frontal lobe lesions do not efficiently organize and develop retrieval strategies.

Conduction aphasia, sensory-motor integration, and phonological short-term memory - An aggregate analysis of lesion and fMRI data

Conduction aphasia is a language disorder characterized by frequent speech errors, impaired verbatim repetition, a deficit in phonological short-term memory, and naming difficulties in the presence of otherwise fluent and grammatical speech output. While traditional models of conduction aphasia have typically implicated white matter pathways, recent advances in lesions reconstruction methodology applied to groups of patients have implicated left temporoparietal zones. Parallel work using functional magnetic resonance imaging (fMRI) has pinpointed a region in the posterior most portion of the left planum temporale, area Spt, which is critical for phonological working memory. Here we show that the region of maximal lesion overlap in a sample of 14 patients with conduction aphasia perfectly circumscribes area Spt, as defined in an aggregate fMRI analysis of 105 subjects performing a phonological working memory task. We provide a review of the evidence supporting the idea that Spt is an interface site for the integration of sensory and vocal tract-related motor representations of complex sound sequences, such as speech and music and show how the symptoms of conduction aphasia can be explained by damage to this system.

Memory performance on the California Verbal Learning Test-II: Findings from patients with focal frontal lesions

Numerous studies have suggested that frontal cortex plays a strategic, rather than an absolute, role in memory performance. Typically, frontal patients are reported to have impaired recall but normal recognition memory. A recent meta-analysis, however, has questioned this conclusion. To further investigate the role of frontal cortex in long-term memory, patients with focal frontal lesions and age- and education-matched controls were tested on a new version of the California Verbal Learning Test (CVLT-II). Frontal patients exhibited a number of deficits on this test, including overall poorer recall, an increased tendency to make intrusions, reduced semantic clustering, and impaired yes/no recognition performance. Further analysis of the error rates in the yes/no recognition task revealed that frontal patients were most likely to mistakenly endorse 2 types of distractors: semantically related words and words from an interference list. These findings are discussed with respect to the role of frontal dysfunction in false recollections and poor source memory, as well as the distinction between the roles of frontal and temporal cortex in long-term memory.

The Role of Inferior Parietal and Inferior Frontal Cortex in Working Memory

Verbal working memory involves two major components: a phonological store that holds auditory-verbal information very briefly and an articulatory rehearsal process that allows that information to be refreshed and thus held longer in short-term memory (A. Baddeley, 1996, 2000; A. Baddeley & G. Hitch, 1974). In the current study, the authors tested two groups of patients who were chosen on the basis of their relatively focal lesions in the inferior parietal (IP) cortex or inferior frontal (IF) cortex. Patients were tested on a series of tasks that have been previously shown to tap phonological storage (span, auditory rhyming, and repetition) and articulatory rehearsal (visual rhyming and a 2-back task). As predicted, IP patients were disproportionately impaired on the span, rhyming, and repetition tasks and thus demonstrated a phonological storage deficit. IF patients, however, did not show impairment on these storage tasks but did exhibit impairment on the visual rhyming task, which requires articulatory rehearsal. These findings lend further support to the working memory model and provide evidence of the roles of IP and IF cortex in separable working memory processes.

Is Problem Solving Dependent on Language

There has been a long-standing debate in the fields of philosophy and cognitive science surrounding the relationship of language to cognition, but the exact nature of this relationship is still unclear (Sokolov, 1968/1972). In the current study, we explored the role of language in one aspect of cognition, namely problem solving, by administering the Wisconsin Card Sorting Test (WCST) to stroke patients with varying degrees of language impairment (Experiment 1) and to normal participants under conditions of articulatory suppression (Experiment 2). In Experiment 1, there was a significant correlation between performance on the WCST and language measures such as comprehension and naming. Demonstrating the specificity of this result, we also found a significant relationship between language performance and another test of problem solving, the Ravens Colored Progressive Matrices, but no relationship between language and a test of visuospatial functioning. In Experiment 2, normal participants were significantly impaired on the WCST under conditions of articulatory suppression, relative to a baseline condition. Together, these findings suggest that language plays a role in complex problem solving, possibly through covert language processes.

Clinical and anatomical correlates of apraxia of speech.

In a previous study (Dronkers, 1996), stroke patients identified as having apraxia of speech (AOS), an articulatory disorder, were found to have damage to the left superior precentral gyrus of the insula (SPGI). The present study sought (1) to characterize the performance of patients with AOS on a classic motor speech evaluation, and (2) to examine whether severity of AOS was influenced by the extent of the lesion. Videotaped speech evaluations of stroke patients with and without AOS were reviewed by two speech-language pathologists and independently scored. Results indicated that patients with AOS made the most errors on tasks requiring the coordination of complex, but not simple, articulatory movements. Patients scored lowest on the repetition of multisyllabic words and sentences that required immediate shifting between place and manner of articulation and rapid coordination of the lips, tongue, velum, and larynx. Last, all patients with AOS had lesions in the SPGI, whereas patients without apraxia of speech did not. Additional involvement of neighboring brain areas was associated with more severe forms of both AOS as well as language deficits, such as aphasia.

What do brain lesions tell us about theories of embodied semantics and the human mirror neuron system

Recent work has been mixed with respect to the notion of embodied semantics, which suggests that processing linguistic stimuli referring to motor-related concepts recruits the same sensorimotor regions of cortex involved in the execution and observation of motor acts or the objects associated with those acts. In this study, we asked whether lesions to key sensorimotor regions would preferentially impact the comprehension of stimuli associated with the use of the hand, mouth or foot. Twenty-seven patients with left-hemisphere strokes and 10 age- and education-matched controls were presented with pictures and words representing objects and actions typically associated with the use of the hand, mouth, foot or no body part at all (i.e., neutral). Picture/sound pairs were presented simultaneously, and participants were required to press a space bar only when the item pairs matched (i.e., congruent trials). We conducted two different analyses: 1) we compared task performance of patients with and without lesions in several key areas previously implicated in the putative human mirror neuron system (i.e., Brodmann areas 4/6, 1/2/3, 21 and 44/45), and 2) we conducted Voxel-based Lesion-Symptom Mapping analyses (VLSM; Bates et al., 2003) to identify additional regions associated with the processing of effector-related versus neutral stimuli. Processing of effector-related stimuli was associated with several regions across the left hemisphere, and not solely with premotor/motor or somatosensory regions. We also did not find support for a somatotopically-organized distribution of effector-specific regions. We suggest that, rather than following the strict interpretation of homuncular somatotopy for embodied semantics, these findings support theories proposing the presence of a greater motor-language network which is associated with, but not restricted to, the network responsible for action execution and observation.

Grey and white matter correlates of picture naming: Evidence from a voxel-based lesion analysis of the Boston Naming Test

A number of recent studies utilizing both functional neuroimaging and lesion analysis techniques in neurologic patients have produced conflicting results with respect to the neural correlates of picture naming. Picture naming involves a number of cognitive processes, from visual perception/recognition to lexical-semantic retrieval to articulation. This middle process, the ability to retrieve a name associated with an object, has been attributed in some cases to posterior portions of the left lateral temporal lobe and in other cases, to anterior temporal cortex. In the current study, we used voxel-based lesion symptom mapping (VLSM) to identify neural correlates of picture naming in a large sample of well-characterized left hemisphere (LH) patients suffering from a range of naming deficits. We tested patients on the Boston Naming Test (BNT), a clinical, standardized measure of picture naming that is widely used in both clinical and research settings. We found that overall performance on the BNT was associated with a network of LH regions that included significant portions of the left anterior to posterior middle temporal gyrus (MTG) and superior temporal gyrus (STG) and underlying white matter, and extended into left inferior parietal cortex. However, when we added covariates to this analysis that controlled for deficits in visual recognition and motor speech in order to isolate brain regions specific to lexical-semantic retrieval, the significant regions that remained were confined almost exclusively to the left mid-posterior MTG and underlying white matter. These findings support the notion that a large network in left peri-Sylvian cortex supports picture naming, but that the left mid-posterior MTG and underlying white matter play a critical role in the core ability to retrieve a name associated with an object or picture.