Andreia V. Faria

Quantitative analysis of gray and white matter in Williams syndrome.

Williams syndrome is a developmental disorder with a genetic basis, which results in an uneven cognitive profile with relatively strong language skills and severely impaired visuospatial abilities. To better understand the brain structure underlying this profile, we compared individuals with Williams syndrome with controls using multimodal neuroimaging data and new analytic methods (diffeomorphic mapping and atlas-based analysis). People with Williams syndrome had basal ganglia atrophy, while the fusiform, the medium temporal gyri, and the cerebellar cortex were relatively preserved. The right superior longitudinal fasciculus, the left frontooccipital fasciculus, the caudate, and the cingulum demonstrated increased fractional anisotropy, whereas the corticospinal tract revealed decreased values. These findings may be linked to the uneven cognitive profile evident in Williams syndrome.

An Area Essential for Linking Word Meanings to Word Forms: Evidence from Primary Progressive Aphasia

We investigated the relationship between deficits in naming and areas of focal atrophy in primary progressive aphasia (a neurodegenerative disease that specifically affects language processing). We tested patients, across multiple input modalities, on traditional naming tasks (picture naming) and more complex tasks (sentence completion with a name, naming in response to a question) and obtained high resolution MRI. Across most tasks, error rates were correlated with atrophy in the left middle and posterior inferior temporal gyrus. Overall, this result converges with prior literature suggesting that this region plays a major role in modality independent lexical processing.

A brief assessment of object semantics in primary progressive aphasia

Background: A cross-culturally valid nonverbal assessment of semantic knowledge is needed. Accurately identifying impairment of object semantics is important for diagnosis of several disorders, including distinguishing semantic variant primary progressive aphasia (svPPA), a neurodegenerative condition characterised by progressive impairment in word comprehension, from logopenic and nonfluent agrammatic variants, which are not associated with impaired object semantics. However, current assessments require culturally specific knowledge. Aims: We developed a cross-culturally valid short form of the Pyramids and Palm Trees Test to assess object semantic memory. We investigated its clinical utility in differentiating the semantic variant of primary progressive aphasia, from the logopenic and nonfluent agrammatic variants. Areas of atrophy associated with poor performance were identified. Methods & Procedures: Fourteen items that rely on knowledge of objects’ defining features were selected from the original 52-item version. The full and short forms were administered to healthy individuals in the US (N = 18), Argentina (N = 20), and Greece (N = 12) and performance was compared. Seventy-eight individuals with primary progressive aphasia in the US completed the short form. Behavioural performance of the svPPA group (N = 24) was compared to other variants. Atlas-based analysis identified regions where atrophy correlated with poor performance in 39 individuals with primary progressive aphasia who had high-resolution magnetic resonance imaging (MRI) scans. Outcomes & Results: Control performance was classified as normal on the short form significantly more often than on the full version. Across groups with primary progressive aphasia, the group with semantic variant performed significantly worse than the groups with logopenic or nonfluent agrammatic variants. Volume in left anterior and inferior temporal cortex correlated with performance. Conclusions: The short-form Pyramids and Palm Trees Test is a clinically relevant, cross-culturally valid assessment of nonverbal object semantics. It can be used to identify semantic impairments, with poor performance associated with atrophy of the temporal lobes.

Patterns of Dysgraphia in Primary Progressive Aphasia Compared to Post-Stroke Aphasia

We report patterns of dysgraphia in participants with primary progressive aphasia that can be explained by assuming disruption of one or more cognitive processes or representations in the complex process of spelling. These patterns are compared to those described in participants with focal lesions (stroke). Using structural imaging techniques, we found that damage to the left extrasylvian regions, including the uncinate, inferior fronto-occipital fasciculus, and sagittal stratum (including geniculostriate pathway and inferior longitudinal fasciculus), as well as other deep white and grey matter structures, was significantly associated with impairments in access to orthographic word forms and semantics (with reliance on phonology-to-orthography to produce a plausible spelling in the spelling to dictation task). These results contribute not only to our understanding of the patterns of dysgraphia following acquired brain damage but also the neural substrates underlying spelling.

Separable systems for recovery of finger strength and control after stroke

Impaired hand function after stroke is a major cause of long-term disability. We developed a novel paradigm that quantifies two critical aspects of hand function, strength, and independent control of fingers (individuation), and also removes any obligatory dependence between them. Hand recovery was tracked in 54 patients with hemiparesis over the first year after stroke. Most recovery of strength and individuation occurred within the first 3 mo. A novel time-invariant recovery function was identified: recovery of strength and individuation were tightly correlated up to a strength level of ~60% of estimated premorbid strength; beyond this threshold, strength improvement was not accompanied by further improvement in individuation. Any additional improvement in individuation was attributable instead to a second process that superimposed on the recovery function. We conclude that two separate systems are responsible for poststroke hand recovery: one contributes almost all of strength and some individuation; the other contributes additional individuation.NEW & NOTEWORTHY We tracked recovery of the hand over a 1-yr period after stroke in a large cohort of patients, using a novel paradigm that enabled independent measurement of finger strength and control. Most recovery of strength and control occurs in the first 3 mo after stroke. We found that two separable systems are responsible for motor recovery of hand: one contributes strength and some dexterity, whereas a second contributes additional dexterity.

White matter tracts critical for recognition of sarcasm

Failure to recognize sarcasm can lead to important miscommunications. Few previous studies have identified brain lesions associated with impaired recognition of sarcasm. We tested the hypothesis that percent damage to specific white matter tracts, age, and education together predict accuracy in sarcasm recognition. Using multivariable linear regression, with age, education, and percent damage to each of eight white matter tracts as independent variables, and percent accuracy on sarcasm recognition as the dependent variable, we developed a model for predicting sarcasm recognition. Percent damage to the sagittal stratum had the greatest weight and was the only independent predictor of sarcasm recognition.

Relatively normal repetition performance despite severe disruption of the left arcuate fasciculus

The arcuate fasciculus (AF) is believed to be fundamental to the neural circuitry behind many important cognitive processes. Connecting Wernickes and Brocas area, these fibers are thought to be especially important for repetition. In this case study we present evidence from a patient that set doubt on these assumptions. We present structural imaging, diffusion tensor imaging, and language data on a patient with a large left-sided stroke and severely damaged left AF who showed intact word repetition and relatively intact sentence repetition performance. Specifically, his sentence repetition is more fluent and grammatical, with less hesitation than spontaneous speech, and with rare omissions only during the longest sentences. These results challenge classical theories that maintain the left AF is the dominant language processing pathway or mechanism for repetition.

Longitudinal imaging and deterioration in word comprehension in primary progressive aphasia: Potential clinical significance

Background: Three variants of primary progressive aphasia (PPA), distinguished by language performance and supportive patterns of atrophy on imaging, have different clinical courses and the prognoses for specific functions. For example, semantic variant PPA alone is distinguished by impaired word comprehension. However, sometimes individuals with high education show normal performance on word-comprehension tests early on, making classification difficult. Furthermore, as the condition progresses, individuals with other variants develop word-comprehension deficits and other behavioural symptoms, making distinctions between variants less clear. Longitudinal brain imaging allows identification of specific areas of atrophy in individual patients, which identifies the location of disease in each patient. Aims: We hypothesised that the areas of atrophy in individual PPA participants would be closely correlated with the decline in word comprehension over time. We propose that areas where tissue volume is correlated with word comprehension are areas that: (1) are essential for word comprehension, (2) compensate for word comprehension in some individuals with semantic variant PPA early in the course, and (3) show atrophy in individuals with logopenic and nonfluent variant PPA only late in the course. Methods and Procedures: Fifteen participants with PPA (five logopenic variant PPA; eight semantic variant PPA; two nonfluent/agrammatic variant PPA; mean age 67.8), underwent high resolution magnetic resonance imaging and cognitive tests at least 9 months apart. The correlations between change in regional volumes and change in auditory word-comprehension scores were investigated using Spearman test. Outcomes & Results: While scores on auditory word comprehension at Time 1 were correlated with volume loss in right and left temporal pole and left inferior temporal cortex (areas of atrophy associated with semantic variant PPA), deterioration in auditory word comprehension from Time 1 to Time 2 was associated with individual atrophy in left middle temporal cortex, left angular gyrus, and right inferior and middle temporal cortex. Conclusions: Progressive atrophy in focal areas surrounding left temporal pole and left inferior temporal cortex, and right homologous area is closely related to progressive decline in auditory word comprehension. These correlations likely reflect areas that compensate for subtle deficits early in the course of semantic variant PPA, as well as areas that are critical for auditory word comprehension that eventually atrophy in individuals with other variants of PPA. Individual patterns of atrophy also help us understand and predict the clinical course of individuals, such as associated behavioural or motor deficits.

Recovery of hand function after stroke: separable systems for finger strength and control

Loss of hand function after stroke is a major cause of long-term disability. Hand function can be partitioned into strength and independent control of fingers (individuation). Here we developed a novel paradigm, which independently quantifies these two aspects of hand function, to track hand recovery in 54 patients with hemiparesis over the first year after their stroke. Most recovery of both strength and individuation occurred in the first three months after stroke. Improvement in strength and individuation were tightly correlated up to a strength level of approximately 60% of the unaffected side. Beyond this threshold, further gains in strength were not accompanied by improvements in individuation. Any observed improvements in individuation beyond the 60% threshold were attributable instead to a second independent stable factor. Lesion analysis revealed that damage to the hand area in motor cortex and the corticospinal tract (CST) correlated more with individuation than with strength. CST involvement correlated with individuation even after factoring out the strength-individuation correlation. The most parsimonious explanation for these behavioral and lesion-based findings is that most strength recovery, along with some individuation, can be attributed to descending systems other than the CST, whereas further recovery of individuation is CST dependent.

Evidence for a subcortical origin of mirror movements after stroke: a longitudinal study

Following a stroke, mirror movements are unintended movements that appear in the non-paretic hand when the paretic hand voluntarily moves. Mirror movements have previously been linked to overactivation of sensorimotor areas in the non-lesioned hemisphere. In this study, we hypothesized that mirror movements might instead have a subcortical origin, and are the by-product of subcortical motor pathways upregulating their contributions to the paretic hand. To test this idea, we first characterized the time course of mirroring in 53 first-time stroke patients, and compared it to the time course of activities in sensorimotor areas of the lesioned and non-lesioned hemispheres (measured using functional MRI). Mirroring in the non-paretic hand was exaggerated early after stroke (Week 2), but progressively diminished over the year with a time course that parallelled individuation deficits in the paretic hand. We found no evidence of cortical overactivation that could explain the time course changes in behaviour, contrary to the cortical model of mirroring. Consistent with a subcortical origin of mirroring, we predicted that subcortical contributions should broadly recruit fingers in the non-paretic hand, reflecting the limited capacity of subcortical pathways in providing individuated finger control. We therefore characterized finger recruitment patterns in the non-paretic hand during mirroring. During mirroring, non-paretic fingers were broadly recruited, with mirrored forces in homologous fingers being only slightly larger (1.76 times) than those in non-homologous fingers. Throughout recovery, the pattern of finger recruitment during mirroring for patients looked like a scaled version of the corresponding control mirroring pattern, suggesting that the system that is responsible for mirroring in controls is upregulated after stroke. Together, our results suggest that post-stroke mirror movements in the non-paretic hand, like enslaved movements in the paretic hand, are caused by the upregulation of a bilaterally organized subcortical system.