Sarah Hirsiger

Cortical Surface Area and Cortical Thickness Demonstrate Differential Structural Asymmetry in Auditory-Related Areas of the Human Cortex

This investigation provides an analysis of structural asymmetries in 5 anatomically defined regions (Heschls gyrus, HG; Heschls sulcus, HS; planum temporale, PT; planum polare, PP; superior temporal gyrus, STG) within the human auditory-related cortex. Volumetric 3-dimensional T1-weighted magnetic resonance imaging scans were collected from 104 participants (52 males). Cortical volume (CV), cortical thickness (CT), and cortical surface area (CSA) were calculated based on individual scans of these anatomical traits. This investigation demonstrates a leftward asymmetry for CV and CSA that is observed in the HG, STG, and PT regions. As regards CT, we note a rightward asymmetry in the HG and HS. A correlation analysis of asymmetry indices between measurements for distinct regions of interest (ROIs) yields significant correlations between CT and CV in 4 of 5 ROIs (HG, HS, PT, and STG). Significant correlation values between CSA and CV are observed for all 5 ROIs. The findings suggest that auditory-related cortical areas demonstrate larger leftward asymmetry with respect to the CSA, while a clear rightward asymmetry with respect to CT is salient in both the primary and the secondary auditory cortex only. In addition, we propose that CV is not an ideal neuromarker for anatomical measurements. CT and CSA should be considered independent traits of anatomical asymmetries in the auditory-related cortex.

Longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging.

Relatively little is known about reliability of longitudinal diffusion‐tensor imaging (DTI) measurements despite growing interest in using DTI to track change in white matter structure. The purpose of this study is to quantify within‐ and between session scan‐rescan reliability of DTI‐derived measures that are commonly used to describe the characteristics of neural white matter in the context of neural plasticity research. DTI data were acquired from 16 cognitively healthy older adults (mean age 68.4). We used the Tract‐Based Spatial Statistics (TBSS) approach implemented in FSL, evaluating how different DTI preprocessing choices affect reliability indices. Test‐Retest reliability, quantified as ICC averaged across the voxels of the TBSS skeleton, ranged from 0.524 to 0.798 depending on the specific DTI‐derived measure and the applied preprocessing steps. The two main preprocessing steps that we found to improve TBSS reliability were (a) the use of a common individual template and (b) smoothing DTI data using a 1‐voxel median filter. Overall our data indicate that small choices in the preprocessing pipeline have a significant effect on test‐retest reliability, therefore influencing the power to detect change within a longitudinal study. Furthermore, differences in the data processing pipeline limit the comparability of results across studies. Hum Brain Mapp 35:4544–4555, 2014.

Reliability and statistical power analysis of cortical and subcortical FreeSurfer metrics in a large sample of healthy elderly

FreeSurfer is a tool to quantify cortical and subcortical brain anatomy automatically and noninvasively. Previous studies have reported reliability and statistical power analyses in relatively small samples or only selected one aspect of brain anatomy. Here, we investigated reliability and statistical power of cortical thickness, surface area, volume, and the volume of subcortical structures in a large sample (N=189) of healthy elderly subjects (64+ years). Reliability (intraclass correlation coefficient) of cortical and subcortical parameters is generally high (cortical: ICCs>0.87, subcortical: ICCs>0.95). Surface-based smoothing increases reliability of cortical thickness maps, while it decreases reliability of cortical surface area and volume. Nevertheless, statistical power of all measures benefits from smoothing. When aiming to detect a 10% difference between groups, the number of subjects required to test effects with sufficient power over the entire cortex varies between cortical measures (cortical thickness: N=39, surface area: N=21, volume: N=81; 10mm smoothing, power=0.8, α=0.05). For subcortical regions this number is between 16 and 76 subjects, depending on the region. We also demonstrate the advantage of within-subject designs over between-subject designs. Furthermore, we publicly provide a tool that allows researchers to perform a priori power analysis and sensitivity analysis to help evaluate previously published studies and to design future studies with sufficient statistical power.

Cerebellar gray and white matter volume and their relation with age and manual motor performance in healthy older adults.

Functional neuroimaging and voxel‐based morphometry studies have confirmed the important role of the cerebellum in motor behavior. However, little is known about the relationship between cerebellar gray (GMv) and white matter (WMv) volume and manual motor performance in aging individuals. This study aims to quantify the relationship between cerebellar tissue volume and manual motor performance.

Structural and functional connectivity in healthy aging: Associations for cognition and motor behavior

Age‐related behavioral declines may be the result of deterioration of white matter tracts, affecting brain structural (SC) and functional connectivity (FC) during resting state. To date, it is not clear if the combination of SC and FC data could better predict cognitive/motor performance than each measure separately. We probed these relationships in the cingulum bundle, a major white matter pathway of the default mode network. We aimed to attain deeper knowledge about: (a) the relationship between age and the cingulums SC and FC strength, (b) the association between SC and FC, and particularly (c) how the cingulums SC and FC are related to cognitive/motor performance separately and combined. We examined these associations in a healthy and well‐educated sample of 165 older participants (aged 64‐85). SC and FC were acquired using probabilistic tractography to derive measures to capture white matter integrity within the cingulum bundle (fractional anisotropy, mean, axial and radial diffusivity) and a seed‐based resting‐state functional MRI correlation approach, respectively. Participants performed cognitive tests measuring processing speed, memory and executive functions, and motor tests measuring motor speed and grip force. Our data revealed that only SC but not resting state FC was significantly associated with age. Further, the cingulums SC and FC showed no relation. Different relationships between cognitive/motor performance and SC/FC separately were found, but no additive effect of the combined analysis of cingulums SC and FC for predicting cognitive/motor performance was apparent. Hum Brain Mapp 37:855–867, 2016.

Regional cerebellar volumetric correlates of manual motor and cognitive function

Cerebellar volume declines with aging. Few studies have investigated age differences in regional cerebellar volume (RCV) and their association with motor and cognitive function. In 213 healthy older adults, we investigated the association of age with motor skills, cognition and RCV. Subsequently, we studied the association of RCV with motor skills and cognition. RCVs were derived from T1-weighted MRI scans using the automated SUIT segmentation method and clustered using principal component analysis (PCA). Motor skill (manual dexterity, tapping speed, bimanual visuomotor coordination, grip force) and cognition (mental rotation, verbal memory, inhibition, mental flexibility) were assessed. Behavioral measures were clustered into compounds using PCA: left hand motor skill, right hand motor skill, verbal memory and mental flexibility, and mental rotation & inhibition. Volume of the rostral middle frontal gyri (rMFG) and premotor areas (PMA) were related to performance for reference. Analyses were adjusted for age, sex, and education. Volume of the cerebellar anterior lobe and top of the superior posterior lobe were positively associated with motor skill. Volume of the bottom part of the posterior superior lobe and the inferior posterior lobe was positively associated with cognition. PMA volume was associated with cognition and motor skill and rMFG volume with motor skill. Although these results did not survive FDR correction, their effect sizes suggest that regional cerebellar volume selectively contributes to cognitive and motor skill. Effect sizes of cerebellar associations with performance were similar to those of rMFG/PMA and performance suggesting parallel contributions to performance.

Neuroanatomical and resting state EEG power correlates of central hearing loss in older adults

To gain more insight into central hearing loss, we investigated the relationship between cortical thickness and surface area, speech-relevant resting state EEG power, and above-threshold auditory measures in older adults and younger controls. Twenty-three older adults and 13 younger controls were tested with an adaptive auditory test battery to measure not only traditional pure-tone thresholds, but also above individual thresholds of temporal and spectral processing. The participants’ speech recognition in noise (SiN) was evaluated, and a T1-weighted MRI image obtained for each participant. We then determined the cortical thickness (CT) and mean cortical surface area (CSA) of auditory and higher speech-relevant regions of interest (ROIs) with FreeSurfer. Further, we obtained resting state EEG from all participants as well as data on the intrinsic theta and gamma power lateralization, the latter in accordance with predictions of the Asymmetric Sampling in Time hypothesis regarding speech processing (Poeppel, Speech Commun 41:245–255, 2003). Methodological steps involved the calculation of age-related differences in behavior, anatomy and EEG power lateralization, followed by multiple regressions with anatomical ROIs as predictors for auditory performance. We then determined anatomical regressors for theta and gamma lateralization, and further constructed all regressions to investigate age as a moderator variable. Behavioral results indicated that older adults performed worse in temporal and spectral auditory tasks, and in SiN, despite having normal peripheral hearing as signaled by the audiogram. These behavioral age-related distinctions were accompanied by lower CT in all ROIs, while CSA was not different between the two age groups. Age modulated the regressions specifically in right auditory areas, where a thicker cortex was associated with better auditory performance in older adults. Moreover, a thicker right supratemporal sulcus predicted more rightward theta lateralization, indicating the functional relevance of the right auditory areas in older adults. The question how age-related cortical thinning and intrinsic EEG architecture relates to central hearing loss has so far not been addressed. Here, we provide the first neuroanatomical and neurofunctional evidence that cortical thinning and lateralization of speech-relevant frequency band power relates to the extent of age-related central hearing loss in older adults. The results are discussed within the current frameworks of speech processing and aging.

Cognitive and neuroanatomical impairments associated with chronic exposure to levamisole-contaminated cocaine

Currently, levamisole is the most common cocaine adulterant worldwide and it is known to induce a variety of adverse side effects. Animal studies and human case reports suggest potential neurotoxicity of the compound but neither neuroanatomical nor cognitive effects of levamisole have been systematically investigated in cocaine users so far. We examined cognitive performance and cortical structural differences between chronic cocaine users with low and high recent exposure to levamisole objectively determined by quantitative toxicological hair analyses. In Study 1, we compared 26 chronic cocaine users with low levamisole exposure (lowLevCU), 49 matched cocaine users with high levamisole exposure (highLevCU), and 78 matched stimulant-naive controls regarding cognitive functioning employing a comprehensive neuropsychological test battery. In Study 2, we investigated cortical thickness by use of T1-weighted MRI in a subgroup of 12 lowLevCU, 17 highLevCU, and 38 stimulant-naive controls. In Study 1, both cocaine user groups showed significant impairments in the cognitive domains of attention and working memory as well as in the global cognitive index. However, highLevCU showed significantly worse executive functions compared to lowLevCU although both groups did not differ in severity of cocaine consumption and other clinical dimensions. Study 2 revealed that highLevCU, displayed reduced cortical thickness specifically in the middle frontal gyrus compared to both controls and lowLevCU. Our results suggest that levamisole exposure during the last months in cocaine users is associated with increased executive function impairments and pronounced thinning of the lateral prefrontal cortex. Consequently, prevention and drug policy-making should aim to reduce levamisole contamination of street cocaine.

Executive Functions in Healthy Older Adults Are Differentially Related to Macro- and Microstructural White Matter Characteristics of the Cerebral Lobes

Aging is associated with microstructural white matter (WM) changes. WM microstructural characteristics, measured with diffusion tensor imaging (DTI), are different in normal appearing white matter (NAWM) and WM hyperintensities (WMH). It is largely unknown how the microstructural properties of WMH are associated with cognition and if there are regional effects for specific cognitive domains. We therefore examined within 200 healthy older participants (a) differences in microstructural characteristics of NAWM and WMH per cerebral lobe; and (b) the association of macrostructural (WMH volume) and microstructural characteristics (within NAWM and WMH separately) of each lobe with measures of executive function and processing speed. Multi-modal imaging (i.e., T1, DTI, and FLAIR) was used to assess WM properties. The Stroop and the Trail Making Test were used to measure inhibition, task-switching (both components of executive function), and processing speed. We observed that age was associated with deterioration of white matter microstructure of the NAWM, most notably in the frontal lobe. Older participants had larger WMH volumes and lowest fractional anisotropy values within WMH were found in the frontal lobe. Task-switching was associated with cerebral NAWM volume and NAWM volume of all lobes. Processing speed was associated with total NAWM volume, and microstructural properties of parietal NAWM, the parietal WMH, and the temporal NAWM. Task-switching was related to microstructural properties of WMH of the frontal lobe and WMH volume of the parietal lobe. Our results confirm that executive functioning and processing speed are uniquely associated with macro- and microstructural properties of NAWM and WMH. We further demonstrate for the first time that these relationships differ by lobar region. This warrants the consideration of these distinct WM indices when investigating cognitive function.