Carole L. Palumbo

Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage : effects of lesion location and test structure on separable cognitive processes

Forty-six patients with single focal lesions (35 frontal, 11 nonfrontal) were administered the Wisconsin Card Sorting Test (WCST) under three conditions of test administration. The three conditions varied in the amount of external support provided via specificity of instructions. The WCST, while a multifactorial test, is specifically sensitive to the effects of frontal lobe damage if deficits in language comprehension and visual-spatial search are controlled. There is also specificity of functioning within the frontal lobes: patients with inferior medial frontal lesions, unilateral or bilateral, were not impaired on the standard measures although they had increased loss of set when informed of the sorting categories. Verbal instructions may provide a probe to improve diagnosis and prognosis, assessment of the potential efficacy of treatment, and the time frame of plasticity of specific cognitive operations.

Broca's area aphasias Aphasia after lesions including the frontal operculum

We report 9 cases of aphasia following lesions in the region of the left frontal operculum. It is not possible to capture their variety of clinical manifestations with the simple labels of “Brocas aphasia” or “Brocas area aphasia.” Analysis of the breakdown of various components of speech and language in these cases suggests that the operculum, lower motor cortex, and subjacent subcortical and periventricular white matter contain critical parts of different language systems. These systems can be independently impaired. There are several common language syndromes that follow damage that includes the left frontal operculum. These syndromes reflect the effects of the direction and extent of the lesion in the various language systems.

Overt propositional speech in chronic nonfluent aphasia studied with the dynamic susceptibility contrast fMRI method.

This study examined activation levels in the left (L) supplementary motor area (SMA) and the right (R) SMA (separately), and activation in nine R perisylvian language homologues during overt, propositional speech in chronic nonfluent aphasia patients. Previous functional imaging studies with a variety of chronic aphasia patients have reported activation in these regions during different language tasks, however, overt propositional speech has not been examined. In the present research, four nonfluent aphasia patients were studied during overt elicited propositional speech at 4-9 years post-single L hemisphere stroke, which spared the SMA. The dynamic susceptibility contrast (DSC) method of functional MRI was used to calculate relative cerebral blood volume (relCBV) for cortical regions of interest (ROIs) during the first-pass bolus of gadolinium during two conditions: (1) pattern (silent viewing of checkerboard patterns) and (2) story (overt, elicited propositional speech describing sequential pictures, which formed a story). During the story condition, controls had significantly higher relCBV in L SMA than in R SMA; aphasics, however, had significantly higher relCBV in R SMA than in L SMA. During the pattern condition, no significant differences were observed between the L SMA and the R SMA for either controls or aphasics. In addition, aphasics had significantly higher relCBV in the R sensorimotor mouth during story than pattern. This R sensorimotor mouth relCBV was also significantly higher in aphasics than controls during story, and the two groups did not differ during pattern. The overall mean relCBV for the nine R perisylvian ROIs was significantly higher for aphasics than controls during both story and pattern. These results suggest that poor modulation, including possible over-activation of R sensorimotor mouth and other R perisylvian language homologues may underlie in part, the hesitant, poorly articulated, agrammatic speech associated with nonfluent aphasia.

Temporal dimensions of consonant and vowel production: an acoustic and CT scan analysis of aphasic speech.

This study explored a number of temporal (durational) parameters of consonant and vowel production in order to determine whether the speech production impairments of aphasics are the result of the same or different underlying mechanisms and in particular whether they implicate deficits that are primarily phonetic or phonological in nature. Detailed analyses of CT scan lesion data were also conducted to explore whether more specific neuroanatomical correlations could be made with speech production deficits. A series of acoustic analyses were conducted including voice-onset time, intrinsic and contrastive fricative duration, and intrinsic and contrastive vowel duration as produced by Brocas aphasics with anterior lesions (A patients), nonfluent aphasics with anterior and posterior lesions (AP patients), and fluent aphasics with posterior lesions (P patients). The constellation of impairments for the anterior aphasics including both the A and AP patients suggests that their disorder primarily reflects an inability to implement particular types of articulatory gestures or articulatory parameters rather than an inability to implement particular phonetic features. They display impairments in the implementation of laryngeal gestures for both consonant and vowel production. These patterns seem to relate to particular anatomical sites involving Brocas area, the anterior limb of the internal capsule, and the lowest motor cortex areas for larynx and tongue. The posterior patients also show evidence of subtle phonetic impairments suggesting that the neural instantiation of speech may require more extensive involvement, including the perisylvian area, than previously suggested.

Neuroimaging and language recovery in stroke.

This article reviews the use of a chronic computed tomography (CT) scan (performed after 2 or 3 months following stroke onset) in assessing a patients potential for recovery of speech and comprehension in the long term (after 6–12 months following stroke onset). Not all aphasia patients recover the ability to produce meaningful speech after a stroke. This article discusses the neuroanatomical areas to be examined on CT scan, in order to predict which stroke patients are not likely to recover meaningful speech, even for as long as 10 years following stroke onset. These neuroanatomical areas are located in deep, subcortical white matter areas; they are not in the cortex. It is important to have information regarding potential for long-term recovery of speech, so that appropriate non-verbal treatment programs can be initiated. A non-verbal computer-assisted treatment program is presented, in which severely affected patients are taught to communicate using pictures and icons on a computer screen.

Visible changes in lesion borders on CT scan after five years poststroke, and long-term recovery in aphasia

This study examined 12 aphasia patients at approximately 1 year poststroke (Time 1) and again at 5-12 years poststroke (Time 2) with language testing and CT scan. Significant increases in naming scores, and phrase length in nonfluent speech were observed after 5 years poststroke. Significant expansion in visible lesion borders (lesion size) was observed after 5 years poststroke; an increase in lesion size of > 1% was present in 9/12 cases (75%). Not one case had a second stroke. Thus, it appears that even though lesion expansion may occur after 5 years poststroke, as long as this expansion is unilateral and gradual, it has no adverse effect on language, and in fact, continued recovery in naming and nonfluent speech may also occur. Long-term recovery patterns in aphasia which may be associated with brain reorganization deserve further study, especially with functional brain imaging techniques.

Interactive effects of apolipoprotein E type 4 genotype and cerebrovascular risk on neuropsychological performance and structural brain changes.

OBJECTIVE We sought to determine whether the presence of the apolipoprotein E type 4 (apoE4) allele, a known risk factor for Alzheimer disease, interacts with cerebrovascular risk factors to produce a disproportionate impairment in neuropsychological (NP) performance and alterations in structural morphometry as measured by magnetic resonance imaging (MRI). METHODS In all, 1995 participants from the community-based Framingham Offspring Cohort participants (mean age 61 years; 1063 women) underwent NP testing and structural MRI in 1999 to 2002. Multivariate linear regression was used to estimate the relationships among Framingham Stroke Risk Profile scores, NP variables, and MRI measures; interaction terms were included to examine modification of these relationships by the presence of the apoE4 allele. All analyses were cross sectional. RESULTS We found significant interactions between the presence of the apoE4 allele and the top sex-specific quartile of the stroke risk profile and their effects on verbal memory (P <or= .001), verbal organization (P <or= .001), nonverbal memory (P=.015), as well as set shifting and complex attention (P=.005). Systolic blood pressure (SBP) was the only individual risk factor significantly linked to these cognitive measures. With the exception of lateral ventricular volume, there were no significant interactions among presence of apoE4, the top sex-specific quartile of the stroke risk profile, and any of the MRI variables. CONCLUSION The apoE4 allele exacerbates the effects of cerebrovascular risk factors on NP function. This relationship appears to be driven by SBP, suggesting that treatment of high SBP could potentially reduce risk of cognitive impairment among those already at increased risk for Alzheimer disease.

Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity.

Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986-1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.

Apolipoprotein Epsilon 4 Allele Modifies Waist-to-Hip Ratio Effects on Cognition and Brain Structure

BACKGROUND This study aimed to determine whether relationships between obesity, as measured by waist-to-hip ratio (WHR), and cognition and brain structure were modified by the apolipoprotein epsilon 4 allele (apoE4). METHODS The sample included 1969 stroke- and dementia-free participants from the Framingham Offspring Cohort who underwent neuropsychological (NP) testing and structural magnetic resonance imaging (MRI) between 1999 and 2002. WHR was categorized into sex-specific quartiles with those in Q4 representing central obesity. Multivariate linear regression estimated the relationships between Q4-WHR, cognitive, and MRI measures; interaction terms examined modification of these relationships by the presence of apoE4. All analyses were cross sectional. RESULTS ApoE4 status significantly modified a number of associations. Specifically, we observed a significant negative relationship between Q4-WHR and a measure of executive function in the apoE4(+) group but not in the apoE4(-) group. Similarly, we observed a stronger negative relationship between Q4-WHR and a measure of memory function for those in the apoE4(+) group compared to those in the apoE4(-) group. In addition, apoE4 status modified the relationship between Q4-WHR and 2 measures of structural brain integrity. First, a paradoxical finding of a negative association between WHR and frontal brain volume that was significant only for those in the apoE4(-) group, and a second finding that WHR was significantly associated with greater white matter hyperintensity volume only in the apoE4(+) group. CONCLUSIONS These findings suggest that associations between central adiposity and both neuropsychological performance and underlying brain structure are highly complex and must be considered in the context of possible modifying genetic influences.

Nasal consonant production in Broca’s and Wernicke’s aphasics: Speech deficits and neuroanatomical correlates

The present study investigated the articulatory implementation deficits of Brocas and Wernickes aphasics and their potential neuroanatomical correlates. Five Brocas aphasics, two Wernickes aphasics, and four age-matched normal speakers produced consonant-vowel-(consonant) real word tokens consisting of [m, n] followed by [i, e, a, o, u]. Three acoustic measures were analyzed corresponding to different properties of articulatory implementation: murmur duration (a measure of timing), amplitude of the first harmonic at consonantal release (a measure of articulatory coordination), and murmur amplitude over time (a measure of laryngeal control). Results showed that Brocas aphasics displayed impairments in all of these parameters, whereas Wernickes aphasics only exhibited greater variability in the production of two of the parameters. The lesion extent data showed that damage in either Brocas area or the insula cortex was not predictive of the severity of the speech output impairment. Instead, lesions in the upper and lower motor face areas and the supplementary motor area resulted in the most severe implementation impairments. For the Wernickes aphasics, the posterior areas (superior marginal gyrus, parietal, and sensory) appear to be involved in the retrieval and encoding of lexical forms for speech production, resulting in increased variability in speech production.