Chivon Anderson

Impaired action knowledge in amyotrophic lateral sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition affecting the motor system, but recent work also shows more widespread cognitive impairment. This study examined performance on measures requiring knowledge of actions, and related performance to MRI cortical atrophy in ALS. Methods: A total of 34 patients with ALS performed measures requiring word-description matching and associativity judgments with actions and objects. Voxel-based morphometry was used to relate these measures to cortical atrophy using high resolution structural MRI. Results: Patients with ALS were significantly more impaired on measures requiring knowledge of actions than measures requiring knowledge of objects. Difficulty on measures requiring action knowledge correlated with cortical atrophy in motor cortex, implicating degraded knowledge of action features represented in motor cortex of patients with ALS. Performance on measures requiring object knowledge did not correlate with motor cortex atrophy. Several areas correlated with difficulty for both actions and objects, implicating these brain areas in components of semantic memory that are not dedicated to a specific category of knowledge. Conclusion: Patients with amyotrophic lateral sclerosis are impaired on measures involving action knowledge, and this appears to be due to at least two sources of impairment: degradation of knowledge about action features represented in motor cortex and impairment on multicategory cognitive components contributing more generally to semantic memory.

Social Cognition, Executive Functioning, and Neuroimaging Correlates of Empathic Deficits in Frontotemporal Dementia

The authors investigated aspects of interpersonal sensitivity and perspective-taking in relation to empathy, social cognitions, and executive functioning in 26 frontotemporal dementia (FTD) patients. Behavioral-variant FTD (bvFTD) patients were significantly impaired on caregiver assessments of empathy, although self-ratings were normal. Progressive nonfluent aphasia and semantic-dementia samples were rarely abnormal. In bvFTD, empathy ratings were found to be correlated with social cognition and executive functioning measures, but not depression. Voxel-based morphometry revealed that reduced empathic perspective-taking was related to bifrontal and left anterior temporal atrophy, whereas empathic emotions were related to right medial frontal atrophy. Findings suggest that bvFTD causes multiple types of breakdown in empathy, social cognition, and executive resources, mediated by frontal and temporal disease.

Non-fluent speech in frontotemporal lobar degeneration

We investigated the cognitive and neural bases of impaired speech fluency, a central feature of primary progressive aphasia. Speech fluency was assessed in 35 patients with frontotemporal lobar degeneration (FTLD) who presented with progressive non-fluent aphasia (PNFA, n=11), semantic dementia (SemD, n=12), or a social and executive disorder without aphasia (SOC/EXEC, n=12). Fluency was quantified as the number of words per minute in an extended, semi-structured speech sample. This was related to language characteristics of the speech sample and to neuropsychological measures. PNFA patients were significantly less fluent than controls and other FTLD patients. Fluency correlated with grammatical expression but not with speech errors or executive difficulty. SemD and SOC/EXEC patients were also less fluent than controls. In SemD, fluency was associated with semantically limited content. In SOC/EXEC, fluency was associated with executive limitations. Voxel-based morphometry analyses of high-resolution MRI related fluency to gray matter volume in left inferior frontal, insula, and superior temporal regions for the entire cohort of FTLD patients. This region overlapped partially distinct atrophic areas in each FTLD subgroup. It thus appears to play a crucial role in speech fluency, which can be interrupted in different ways in different FTLD subgroups.

Reversal of the concreteness effect in semantic dementia

Patients with semantic dementia (SD) have a striking impairment in semantic memory, but the basis for this deficit is unclear. We examined semantic memory for concrete and abstract verbs with a two-alternative, forced-choice measure of lexical semantic associative knowledge. Patients with SD had significantly greater difficulty with concrete verbs (z = –3.33) than with abstract verbs (z = –2.05), a “reversal of the concreteness effect” that was present in a majority of individual patients. The subgroup of SD patients with imaging had significant cortical thinning in the anterior and inferolateral portions of the temporal lobes. These areas of visual association cortex may be important for storing and processing visual features for word meaning. Moreover, poor performance with concrete relative to abstract verbs correlated with cortical thinning of the right anterior temporal lobe in SD, suggesting that this region may contribute to storing and processing visual semantic features. These observations raise the possibility that degraded visual feature knowledge contributes in part to the impaired comprehension of concrete words in SD.

Apathy in frontotemporal dementia: Behavioral and neuroimaging correlates

We investigated the occurrence of goal-directed motivational change in the form of apathy in patients with frontotemporal dementia (FTD), particularly those with behavioral variant social and executive deficits (bvFTD). Standardized behavioral inventory was employed to survey and compare apathy ratings from patients and caregivers. In cases of bvFTD, apathy ratings were further related to measures of social cognition, executive function, and atrophy on brain MRI. Results indicated that caregivers rated bvFTD patients as having significantly elevated apathy scores though patient self-ratings were normal. Caregiver and self-ratings of FTD samples with progressive nonfluent aphasia and semantic dementia did not differ from healthy controls and their informants. In the bvFTD sample, caregiver apathy scores were not correlated with general cognitive screening or depression scores, but were significantly correlated with social cognition and executive function measures. Voxel-based morphometry revealed that apathy ratings in bvFTD were related to prominent atrophy in the right caudate (including the ventral striatum), the right temporo-parietal junction, right posterior inferior and middle temporal gyri, and left frontal operculum- anterior insula region. Findings suggest that bvFTD is associated with a significant breakdown in goal-directed motivated behavior involving disruption of cortical-basal ganglia circuits that is also related to social and executive function deficits.

The role of ventral medial prefrontal cortex in social decisions: Converging evidence from fMRI and frontotemporal lobar degeneration

The ventral medial prefrontal cortex (vmPFC) has been implicated in social and affectively influenced decision-making. Disease in this region may have clinical consequences for social judgments in patients with frontotemporal lobar degeneration (FTLD). To test this hypothesis, regional cortical activation was monitored with fMRI while healthy adults judged the acceptability of brief social scenarios such as cutting into a movie ticket line or going through a red light at 2 AM. The scenarios described: (i) a socially neutral condition, (ii) a variant of each scenario containing a negatively valenced feature, and (iii) a variant containing a positively valenced feature. Results revealed that healthy adults activated vmPFC during judgments of negatively valenced scenarios relative to positive scenarios and neutral scenarios. In a comparative behavioral study, the same social decision-making paradigm was administered to patients with a social disorder due to FTLD. Patients differed significantly from healthy controls, specifically showing less sensitivity to negatively valenced features. Comparative anatomical analysis revealed considerable overlap of vmPFC activation in healthy adults and vmPFC cortical atrophy in FTLD patients. These converging results support the role of vmPFC in social decision-making where potentially negative consequences must be considered.

Spatiotemporal normalization for longitudinal analysis of gray matter atrophy in frontotemporal dementia

We present a unified method, based on symmetric diffeomorphisms, for studying longitudinal neurodegeneration. Our method first uses symmetric diffeomorphic normalization to find a spatiotemporal parameterization of an individuals image time series. The second step involves mapping a representative image or set of images from the time series into an optimal template space. The template mapping is then combined with the intrasubject spatiotemporal map to enable pairwise statistical tests to be performed on a population of normalized time series images. Here, we apply this longitudinal analysis protocol to study the gray matter atrophy patterns induced by frontotemporal dementia (FTD). We sample our normalized spatiotemporal maps at baseline (time zero) and time one year to generate an annualized atrophy map (AAM) that estimates the annual effect of FTD. This spatiotemporal normalization enables us to locate neuroanatomical regions that consistently undergo significant annual gray matter atrophy across the population. We found the majority of annual atrophy to occur in the frontal and temporal lobes in our population of 20 subjects. We also found significant effects in the hippocampus, insula and cingulate gyrus. Our novel results, significant at p < 0.05 after false discovery rate correction, are represented in local template space but also assigned Talairach coordinates and Brodmann and Anatomical Automatic Labeling (AAL) labels. This paper shows the statistical power of symmetric diffeomorphic normalization for performing deformation-based studies of longitudinal atrophy.