Cortical Regions Of Interest Research Articles

Alpha and theta mechanisms operating in internal-external attention competition.

Attention is the ability to prioritize a set of information at expense of others and can be internally- or externally-oriented. Alpha and theta oscillations have been extensively implicated in attention. However, it is unclear how these oscillations operate when sensory distractors are presented continuously during task-relevant internal processes, in close-to-real-life conditions. Here, EEG signals from healthy participants were obtained at rest and in three attentional conditions, characterized by the execution of a mental math task (internal attention), presentation of pictures on a monitor (external attention), and task execution under the distracting action of picture presentation (internal-external competition). Alpha and theta power were investigated at scalp level and at some cortical regions of interest (ROIs); moreover, functional directed connectivity was estimated via spectral Granger Causality. Results show that frontal midline theta was distinctive of mental task execution and was more prominent during competition compared to internal attention alone, possibly reflecting higher executive control; anterior cingulate cortex appeared as mainly involved and causally connected to distant (temporal/occipital) regions. Alpha power in visual ROIs strongly decreased in external attention alone, while it assumed values close to rest during competition, reflecting reduced visual engagement against distractors; connectivity results suggested that bidirectional alpha influences between frontal and visual regions could contribute to reduce visual interference in internal attention. This study can help to understand how our brain copes with internal-external attention competition, a condition intrinsic in the human sensory-cognitive interplay, and to elucidate the relationships between brain oscillations and attentional functions/dysfunctions in daily tasks.

Cognitive status, brain amyloid pathology, and neurodegeneration are associated with altered white matter microstructure

AbstractBackgroundBrain amyloid (AB) and neurodegeneration (assessed using PET and MRI) are key AD pathology biomarkers, particularly during transitions from cognitively unimpaired (CU) to cognitively impaired (CI) states. Importantly, the role of brain white matter microstructural measures in these changes, such as those derived from neurite orientation dispersion and density imaging (NODDI), are poorly understood. We explored roles of cognitive status, brain amyloid pathology, and neurodegeneration on NODDI Free Water (FW), a potential neuroinflammation biomarker.MethodParticipants enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort (N=74, Table 1) underwent neuropsychological assessment, T1/NODDI MRI, and PiB PET. Participants were adjudicated as cognitively impaired (MCI or AD) or unimpaired using NIA‐AA criteria. T1 MRI were processed (FreeSurfer v5.3) to generate regions of interest (ROIs). An “AD‐signature” cortical thickness value was calculated, and thresholded to classify participants as neurodegeneration‐positive (N+) or ‐negative (N‐). A set of AD‐sensitive cortical ROIs was used to extract mean PET signal, which was thresholded to adjudicate AB positivity (AB‐/AB+). NODDI was processed to yield parameter maps using AMICO; mean isotropic volume fraction (FW) was calculated over a set of white matter tract ROIs. A two‐way ANOVA/ANCOVA (covariates: age, sex, education) assessed effects of neurodegeneration and AB on FW (N+/N‐ x AB+/AB‐), and a two‐way ANOVA/ANCOVA assessed effects of cognitive impairment and AB on FW (CU/CI x AB+/AB‐).ResultWe first examined effects of neurodegeneration and AB on NODDI FW. We found a significant main effect of neurodegeneration (p=.042), such that N+ had higher FW; this was marginal after adjustment (p=.07). We also observed a significant main effect of AB (p<.001; adjusted p=.012), with AB+ having higher FW. There was no significant interaction. We next explored how cognitive status and AB interacted on FW. We found a significant main effect of cognitive impairment, with CI having higher FW (p=.018; adjusted p=.013). We also found an interaction between diagnosis and AB (p=.037; adjusted p=.044) such that among AB+ individuals, presence of CI related to increased FW (Figure 1).ConclusionNODDI FW increases were significantly affected by the presence of neurodegeneration, AB positivity, and cognitive impairment.

Mediterranean versus western diet effects on cerebral cortical thickness and volume in cynomolgus macaques

AbstractBackgroundAssociations between diet, cognitive decline and neurodegenerative disease, including Alzheimer’s Disease (AD), have been reported, but whether these relationships are causal is difficult to determine in human studies. Cynomolgus macaques (Macaca fascicularis), like humans, are omnivorous, have complex central nervous systems, and are susceptible to diet‐induced diseases. Similar to humans, these nonhuman primates accumulate amyloid and tauopathies with age, and diabetes accelerates age‐related amyloid accumulation. Thus, these primates are appropriate models for investigations of diet effects on the brain.MethodUsing structural magnetic resonance imaging, we examined diet effects on brain anatomy by measuring the thicknesses and volumes of AD‐signature cortical regions of interest (ROIs) in 38 middle‐aged females, at baseline and after consumption of either a Mediterranean (MED) or Western (WEST) diet for 36 months (∼ equivalent to a 9‐year follow up in humans).ResultUsing repeated measures analysis, cortical thicknesses were significantly increased in the WEST diet group in the angular gyrus (p<0.001), inferior temporal gyrus (p<0.001), middle temporal gyrus (p<0.001), superior temporal gyrus (p<0.001), supramarginal gyrus (p<0.001), fusiform gyrus (p<0.01), precuneus (p<0.001), parahippocampal gyrus (p<0.01), and an AD meta‐ROI (p<0.001). WEST diet also resulted in increases in total brain volume (p<0.02) and gray matter (p<0.01) and decreases in cerebrospinal fluid (p<0.01), white matter (p<0.01), and deep gray matter (striatum and thalamus) (p<0.05). In contrast to the patterns observed in the WEST diet group, thicknesses and volumes generally remained unchanged between baseline and 31 months treatment in animals consuming the MED diet.ConclusionTaken together, these findings demonstrate that WEST diets likely induce widespread structural shifts, which may increase risk of cognitive decline and neuropathology; whereas MED diets may exact a stabilizing influence on the brain. This study provides important insights about the significance of diet on brain structure, and lays the groundwork for future investigations to uncover the molecular underpinnings of diet‐induced changes in the brain.

Whole brain volume and cortical thickness abnormalities in Wilson's disease: a clinical correlation study.

Wilson's disease (WD) is an inherited autosomal recessive disorder of copper metabolism, and its neurological and neuropsychiatric manifestations are associated with copper accumulation in brain. A few neuroimaging studies have shown that gray matter atrophy in WD affects both subcortical structures and cortex. This study aims to quantitatively evaluate the morphometric brain abnormalities in patients with WD in terms of whole brain volume and cortical thickness and their associations with clinical severity of WD. Thirty patients clinically diagnosed as WD with neurological manifestations and 25 healthy controls (HC) were recruited. 3D T1-weighted images were segmented into 276 whole-brain regions of interest (ROIs) and 68 cortical ROIs. WD-vs-HC group comparisons were then conducted for each ROI. The associations between those morphometric measurements and the Global Assessment Scale (GAS) score for WD were analyzed. Compared with HC, significant WD-related volumetric decreases were found in the bilateral subcortical nuclei (putamen, globus pallidus, caudate nucleus, substantia nigra, red nucleus and thalamus), diffuse white matter and several gray matter regions. WD patients showed reduced cortical thickness in the left precentral gyrus and the left insula. Further, the volumes of the right globus pallidus, bilateral putamen, right external capsule and left superior longitudinal fasciculus were negatively correlated with GAS. Our results indicated that significant WD-related morphometric abnormalities were quantified in terms of whole-brain volumes and cortical thicknesses, some of which correlated significantly to the clinical severity of WD. Those morphometrics may provide a potentially effective biomarker of WD.

Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: Results from the UK7T study

IntroductionWe present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's “Travelling Heads” study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5–3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. MethodsTen healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each “home” site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. Results and DiscussionMean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001–0.005 ppm (χ) and 0.0005–0.001 ms−1 (R2*). For χ this is 2.1–4.8 fold better than 3T reports, and 1.1–3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. ConclusionThe harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

Investigation of local white matter abnormality in Parkinson’s disease by using an automatic fiber tract parcellation

The deficits of white matter (WM) microstructure are involved during Parkinson’s disease (PD) progression. Most current methods identify key WM tracts relying on cortical regions of interest (ROIs). However, such ROI methods can be challenged due to low diffusion anisotropy near the gray matter (GM), which could result in a low sensitivity of tract identification. This work proposes an automatic WM parcellation method to improve the accuracy of WM tract identification and locate abnormal tracts by using sensitive features. The proposed method consists of 1) whole brain WM parcellation using an established fiber clustering method, without using any ROIs, 2) features of fasciculus were calculated to quantify diffusion measures at each equal cross-section along the whole cluster. Then, we use the proposed features to investigate the WM difference in PD compared with healthy controls (HC). We also use these features to investigate the relationship of clinical symptoms and specific fiber tracts. The novelty of the proposed method is that it automatically identifies the abnormal WM fibers in cluster degree. Experiment results indicated that the proposed method had advantage in detecting the local WM abnormality by performing between-group statistical analysis in 30 patients with PD and 28 HC. We found 13 hemisphere clusters and 8 commissural clusters had significant group difference (p < 0.05, corrected by FDR method) in local regions, which belonged to multiple fiber tracts including cingulum bundle (CB), inferior occipito-frontal fasciculus (IoFF), corpus callosum (CC), external capsule (EC), uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and thalamo front (TF). We also found clusters that had relevance with clinical indices of cognitive function (2 clusters), athletic function (6 clusters), and depressive state (2 clusters) in these significant clusters. From the experiment results, it confirmed the ability of the proposed method to identify potential WM microstructure abnormality.

Brain 18F-FDG PET analysis via interval-valued reconstruction: proof of concept for Alzheimer’s disease diagnosis

We propose an innovative approach for 18F-FDG PET analysis based on an interval-valued reconstruction of 18F-FDG brain distribution. Its diagnostic performance for Alzheimer's disease (AD) diagnosis with comparison to a validated post-processing software was assessed. Brain 18F-FDG PET data from 26 subjects were acquired in a clinical routine setting. Raw data were reconstructed using an interval-valued version of the ML-EM algorithm called NIBEM that stands for Non-Additive interval-based expectation maximization. Subject classification was obtained via interval-based statistical comparison (intersection ratio, IR) between cortical regions of interest (ROI) including parietal, temporal, and temporo-mesial cortices and a reference region, the sub-cortical grey nuclei, known not to be affected by AD. In parallel, PET images were post-processed using a validated automated software based on the computation of ROI normalized uptake ratios standard deviation (SUVr SD) with reference to a healthy control database (Siemens Scenium). Clinical diagnosis made during follow-up was considered as the gold-standard for patient classification (16 healthy controls and 10 AD patients). Both methods provided cortical ROI indices that were significantly different between controls and AD patients. The area under the ROC curve for control/AD classification was statistically identical (0.96 for NIBEM IR and 0.95 for Scenium SUVr SD). At the optimal threshold, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were, respectively, 100%, 88%, 92%, 83%, and 100% for both Scenium SUVr SD and NIBEM IR methods. This preliminary study shows that interval-valued reconstruction allows self-consistent analysis of brain 18F-FDG PET data, yielding diagnostic performances that seem promising with respect to those of a commercial post-processing software based on SUVr SD analysis.

1160 Improved Daytime Sleepiness Following Daily Morning Blue Light Therapy Is Associated With Altered Resting-state Network Connectivity

Abstract Introduction Light exposure, particularly blue wavelength light, has consistent positive effects on daytime sleepiness following mild traumatic brain injuries (mTBIs). While self-perceived improvements in daytime sleepiness are well-documented, the neurobiological underpinnings are not well understood. The purpose of this study was to localize changes in functional connectivity after daily morning blue light therapy (BLT) and to associate these changes with improvements in post-mTBI daytime sleepiness. Methods 29 individuals with a history of mTBI were randomized to receive either BLT (n=13) or placebo amber light (ALT; n=16). All participants self-reported daytime sleepiness (Epworth Sleepiness Scale (ESS); lower is better) and underwent resting-state functional magnetic resonance imaging at pre- and post-treatment. Whole-brain functional connectivity (FC) was estimated as the correlations between 400 cortical regions of interest (ROIs) assigned to 7 resting-state networks. A two-sample T-test for post-treatment ROI-to-ROI FC identified target connections (FDR corrected p&amp;lt;0.01). Post-treatment ESS scores and FC for these connections were correlated for treatment-related brain-behavior associations (uncorrected p&amp;lt;0.05). Results Lower FC after BLT in 4 ROI-to-ROI connections linking the default mode and visual networks was associated with lower ESS scores. Higher FC after BLT in 9 ROI-to-ROI connections linking attention, cognitive control, and visual networks was also associated with lower ESS scores. Conclusion BLT resulted in decreased self-reported daytime sleepiness, which was associated with decoupling of the default mode and visual networks as well as increased connectivity between and within attention and cognitive control networks, suggesting potentially improved attention to relevant stimuli and cognitive processes and less internal mentation. These associations may contribute to improved alertness, attention, and cognitive performance following a mTBI. Further work is needed to identify the optimal timing and dosage of BLT to maximize these outcomes. Support This study was funded by an award to Dr. Killgore from the US Army Medical Research and Materiel Command (USAMRMC; award number: W81XWH-14-1-0571).

Individual differences in white and grey matter structure associated with verbal habits of thought

Modality specific encoding habits account for a significant portion of individual differences reflected in functional activation during cognitive processing. Yet, little is known about how these habits of thought influence long-term structural changes in the brain. Traditionally, habits of thought have been assessed using self-report questionnaires such as the visualizer-verbalizer questionnaire. Here, rather than relying on subjective reports, we measured habits of thought using a novel behavioral task assessing attentional biases toward picture and word stimuli. Hypothesizing that verbal habits of thought are reflected in the structural integrity of white matter tracts and cortical regions of interest, we used diffusion tensor imaging and volumetric analyses to assess this prediction. Using a whole-brain approach, we show that word bias is associated with increased volume in several bilateral language regions, in both white and grey matter parcels. Additionally, connectivity within white matter tracts within an a priori speech production network increased as a function of word bias. These results demonstrate long-term structural and morphological differences associated with verbal habits of thought.

S205. A TRANSLATIONAL HOMER 1A-BASED NETWORK APPROACH: IMAGING HOW HALOPERIDOL MODULATES GLUTAMATE SYSTEM FUNCTIONAL CONNECTIVITY

BackgroundSchizophrenia has been conceptualized both as synaptic plasticity and a functional connectivity disorder. Data on brain connectivity can be rendered in the form of network models. In our study we want to evaluate a particular kind of the structural and functional interaction between region of interest (ROI) relevant to schizophrenia pathophysiology: we evaluated the expression of Immediate Early Gene (IEG), Homer1a (H1a), in the different ROI and its functional interaction after Haloperidol (antipsychotic drug) acute administration. H1a is an IEG expressed in an activity-dependent manner, coding for a protein involved in the activity-induced reorganization of glutamatergic synapses.MethodsSprague-Dawley rats were randomly assigned to two treatment groups (n=23), receiving vehicle (NaCl 0.9%; VEH) or haloperidol 0.8 mg/kg (HAL) i.p. injection. H1a induction was evaluated using in situ hybridization. Signal intensity analysis was performed in 34 ROIs in the cortex, in the caudate-putamen and the nucleus accumbens. Student’s t-test was used to detect treatment effects. A signal correlation analysis was performed, computing all possible pairwise Pearson correlations among ROIs separately in the two groups. Using significant correlations, two networks were created for HAL and VEH groups, and their network, node, and edge properties were assessed.ResultsBonferroni-corrected Student’s t-tests revealed statistically significant differences between the two treatment groups. Haloperidol significantly induced Homer1a gene expression compared to vehicle in all ROIs of the striatum (dmCP: p<.0001, t=9.089, df=44; dlCP: p<.0001, t=10.684, df=44; vlCP: p<.0001, t=10.870, df=44; vmCP: p<.0001, t=9.760, df=44; AcCo: p<.0001, t=8,573, df= 44; AcSh: p<.0001, t=6.615, df=44), a result that is consistent with our previous observations. No significant statistical differences were detected among cortical ROIs explored. Correlations between dmCP-AcSh, dlCP-AcSh, vlCP-AcCo, vlCP-AcSh and vmCP-AcSh were significantly different between the VEH and the HAL group (p<.01); correlations between I-vlCP and dlCP-AcCo were also significantly different between the two treatment groups (p<.05); the I-dlCP and I-vmCP showed a trend towards significance.DiscussionHaloperidol acute administration led to a modification of the gene expression pattern in the brain regions considered herein, and consequently to differential functional connectivity. The observed disruption in the functional correlations of the nucleus accumbens may play a role in the affective, motivational and emotional consequences of haloperidol administration, with the loss of functional correlations with the lateral subregions of the caudate-putamen being potentially more relevant to the motor side-effects of haloperidol. These functional connectivity changes are potentially related to neural activity and synaptic plasticity within the glutamate system and may play a role in antipsychotic therapeutic and side effects. As far as we know, this is the first network analysis study on after haloperidol acute treatment of a gene deeply correlated to dendritic spine architecture.

Imaging Cortical Dopamine Transmission in Cocaine Dependence: A [11C]FLB 457–Amphetamine Positron Emission Tomography Study

BackgroundPositron emission tomography studies have demonstrated less dopamine D2/3 receptor availability and blunted psychostimulant-induced dopamine release in cocaine-dependent subjects (CDSs). No studies in CDSs have reported the in vivo status of D2/3 and dopamine release in the cortex. Basic and functional imaging studies suggest a role for prefrontal cortical dopaminergic abnormalities in impaired executive function and relapse in cocaine dependence. We used [11C]FLB 457 positron emission tomography and amphetamine to measure cortical D2/3 receptors and dopamine release in CDSs. Methods[11C]FLB 457 and positron emission tomography were used to measure D2/3 receptor binding potential in cortical regions of interest in recently abstinent CDSs (n = 24) and healthy control subjects (n = 36) both before and after 0.5 mg kg−1 of oral d-amphetamine. Binding potential relative to nondisplaceable uptake (BPND) and binding potential relative to total plasma concentration (BPP) were derived using an arterial input function-based kinetic analysis. Cortical dopamine release in regions of interest was measured as the change in BPND and BPP after amphetamine. ResultsBaseline D2/3 receptor availability (BPP and BPND) and amphetamine-induced dopamine release (ΔBPND and ΔBPP) were significantly lower in the cortical regions in CDSs compared with healthy control subjects. Fewer D2/3 receptors and less dopamine release in CDSs were not associated with performance on working memory and attention tasks. ConclusionsThe results of this study suggest that deficits in dopamine D2/3 transmission involve the cortex in cocaine dependence. Further studies to understand the clinical relevance of these findings are warranted.

High-resolution PET imaging reveals subtle impairment of the serotonin transporter in an early non-depressed Parkinson\u2019s disease cohort

PurposeThe serotonin transporter (SERT) is a biochemical marker for monoaminergic signaling in brain and has been suggested to be involved inthe pathophysiology of Parkinson’s disease (PD). The aim of this PET study was to examine SERT availability in relevant brain regions in early stages ofnon-depressed PD patients.MethodsIn a cross-sectional study, 18 PD patients (13 M/5F, 64 ± 7 years, range 46–74 years, disease duration 2.9 ± 2.6 years; UPDRS motor 21.9 ± 5.2) and 20 age- and gender-matched healthy control (HC) subjects (15 M/5F, 61 ± 7 years, range 50–72 years) were included. In a subsequent longitudinal phase, ten of the PD patients (7 M/3F, UPDRS motor 20.6 ± 6.9) underwent a second PET measurement after 18–24 months. After a 3-T MRI acquisition, baseline PET measurements were performed with [11C]MADAM using a high-resolution research tomograph. The non-displaceablebinding potential (BPND) was chosen as the outcome measure and was estimated at voxel level on wavelet-aided parametric images, by using the Logan graphical analysis and the cerebellum as reference region. A molecular template was generated to visualize and define different subdivisions of the raphe nuclei in the brainstem. Subortical and cortical regions of interest were segmented using FreeSurfer. Univariate analyses and multivariate network analyses were performed on the PET data.ResultsThe univariate region-based analysis showed no differences in SERT levels when the PD patients were compared with the HC neither at baseline or after 2 years of follow-up. The multivariate network analysis also showed no differences at baseline. However, prominent changes in integration and segregation measures were observed at follow-up, indicating a disconnection of the cortical and subcortical regions from the three nuclei of the raphe.ConclusionWe conclude that the serotoninergic system in PD patients seems to become involved with a network dysregulation as the disease progresses, suggesting a disturbed serotonergic signaling from raphe nuclei to target subcortical and cortical regions.

Behavioral deficits in left hemispatial neglect are related to a reduction of spontaneous neuronal activity in the right superior parietal lobule

Focal brain lesions may induce dysfunctions in distant brain regions leading to behavioral impairments. Based on this concept of ‘diaschisis’, spatial neglect following stroke has been related to structural damage of the right-lateralized ventral attention network (VAN) and disrupted inter-hemispheric functional connectivity (FC) in the bilateral dorsal attention network (DAN). We questioned whether neglect-related behavioral deficits may be determined by local dysfunction of a specific region within these brain networks.We investigated acute right-hemisphere stroke patients with left hemispatial neglect using resting-state functional MRI, neuropsychological tests of spatial attention and clinical assessment of neglect-related functional disability. In addition to conventional FC analyses between different cortical regions of interest (ROIs) in the DAN/VAN, we extracted the fractional amplitude of low frequency fluctuations (fALFF) from each ROI as a marker of regional spontaneous neuronal activity. Although DAN regions (as opposed to the VAN regions) were largely spared from structural brain damage, they exhibited a significant reduction of inter-hemispheric FC. However, significant fMRI-behavior correlations were revealed specifically for the fALFF of one DAN-ROI in the right superior parietal lobule (SPL): the smaller the fALFF in the right posterior intraparietal sulcus, the more severe the patient's pathological attention bias and neglect-related functional impairment.In line with ‘diaschisis’, our findings confirm a crucial role of the non-lesioned but dysfunctional right SPL for the emergence of spatial neglect and its behavioral consequences. They further support targeting the SPL dysfunction by non-invasive brain stimulation in neglect rehabilitation.

Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia.

Although amyloid-β (Aβ) and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear. To examine associations of Aβ and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia. Restriction spectrum imaging, cerebrospinal fluid Aβ, and longitudinal cognitive data were collected on 23 healthy controls and 13 individuals with mild cognitive impairment or mild to moderate Alzheimer's disease. Neurite density (ND) and isotropic free water diffusion (IF) were computed in fiber tracts and cortical regions of interest. We examined associations of Aβ with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of Aβ on cognitive decline. Lower ND in limbic and association fibers and higher medial temporal lobe IF predicted baseline impairment and longitudinal decline across multiple cognitive domains. ND and IF predicted cognitive outcomes after adjustment for Aβ or whole-brain microstructure. Correlations between microstructure and cognition were present for both amyloid-positive and amyloid-negative individuals. Aβ correlated with whole-brain, rather than regional, ND and IF. Aβ correlates with widespread microstructural brain changes, whereas regional microstructure correlates with cognitive decline. Microstructural abnormalities predict cognitive decline regardless of amyloid, and may inform about neural injury leading to cognitive decline beyond that attributable to amyloid.

Altered thalamocortical structural connectivity in persons with schizophrenia and healthy siblings

Schizophrenia has long been framed as a disorder of altered brain connectivity, with dysfunction in thalamocortical circuity potentially playing a key role in the development of the illness phenotype, including psychotic symptomatology and cognitive impairments. There is emerging evidence for functional and structural hypoconnectivity between thalamus and prefrontal cortex in persons with schizophrenia spectrum disorders, as well as hyperconnectivity between thalamus and sensory and motor cortices. However, it is unclear whether thalamocortical dysconnectivity is a general marker of vulnerability to schizophrenia or a specific mechanism of schizophrenia pathophysiology. This study aimed to answer this question by using diffusion-weighted imaging to examine thalamocortical structural connectivity in 22 persons with schizophrenia or schizoaffective disorder (SZ), 20 siblings of individuals with a schizophrenia spectrum disorder (SIB), and 44 healthy controls (HC) of either sex. Probabilistic tractography was used to quantify structural connectivity between thalamus and six cortical regions of interest. Thalamocortical structural connectivity was compared among the three groups using cross-thalamic and voxel-wise approaches. Thalamo-prefrontal structural connectivity was reduced in both SZ and SIB relative to HC, while SZ and SIB did not differ from each other. Thalamo-motor structural connectivity was increased in SZ relative to SIB and HC, while SIB and HC did not differ from each other. Hemispheric differences also emerged in thalamic connectivity with motor, posterior parietal, and temporal cortices across all groups. The results support the hypothesis that altered thalamo-prefrontal structural connectivity is a general marker of vulnerability to schizophrenia, whereas altered connectivity between thalamus and motor cortex is related to illness expression or illness-related secondary factors.

Damage to the structural connectome reflected in resting-state fMRI functional connectivity.

The relationship between structural and functional connectivity has been mostly examined in intact brains. Fewer studies have examined how differences in structure as a result of injury alters function. In this study we analyzed the relationship of structure to function across patients with stroke among whom infarcts caused heterogenous structural damage. We estimated relationships between distinct brain regions of interest (ROIs) from functional MRI in two pipelines. In one analysis pipeline, we measured functional connectivity by using correlation and partial correlation between 114 cortical ROIs. We found fMRI-BOLD partial correlation was altered at more edges as a function of the structural connectome (SC) damage, relative to the correlation. In a second analysis pipeline, we limited our analysis to fMRI correlations between pairs of voxels for which we possess SC information. We found that voxel-level functional connectivity showed the effect of structural damage that we could not see when examining correlations between ROIs. Further, the effects of structural damage on functional connectivity are consistent with a model of functional connectivity, diffusion, which expects functional connectivity to result from activity spreading over multiple edge anatomical paths.

A Novel 2D Standard Cartesian Representation for the Human Sensorimotor Cortex

For some experimental approaches in brain imaging, the existing normalization techniques are not always sufficient. This may be the case if the anatomical shape of the region of interest varies substantially across subjects, or if one needs to compare the left and right hemisphere in the same subject. Here we propose a new standard representation, building upon existing normalization methods: Cgrid (Cartesian geometric representation with isometric dimensions). Cgrid is based on imposing a Cartesian grid over a cortical region of interest that is bounded by anatomical (atlas-based) landmarks. We applied this new representation to the sensorimotor cortex and we evaluated its performance by studying the similarity of activation patterns for hand, foot and tongue movements between subjects, and similarity between hemispheres within subjects. The Cgrid similarities were benchmarked against the similarities of activation patterns when transformed into standard MNI space using SPM, and to similarities from FreeSurfer’s surface-based normalization. For both between-subject and between-hemisphere comparisons, similarity scores in Cgrid were high, similar to those from FreeSurfer normalization and higher than similarity scores from SPM’s MNI normalization. This indicates that Cgrid allows for a straightforward way of representing and comparing sensorimotor activity patterns across subjects and between hemispheres of the same subjects.

Longitudinal flortaucipir ([18F]AV-1451) PET imaging in primary progressive apraxia of speech

Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.

A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum

An important aspect of network-based analysis is robust node definition. This issue is critical for functional brain network analyses, as poor node choice can lead to spurious findings and misleading inferences about functional brain organization. Two sets of functional brain nodes from our group are well represented in the literature: (1) 264 volumetric regions of interest (ROIs) reported in Power et al., 2011, and (2) 333 cortical surface parcels reported in Gordon et al., 2016. However, subcortical and cerebellar structures are either incompletely captured or missing from these ROI sets. Therefore, properties of functional network organization involving the subcortex and cerebellum may be underappreciated thus far. Here, we apply a winner-take-all partitioning method to resting-state fMRI data to generate novel functionally-constrained ROIs in the thalamus, basal ganglia, amygdala, hippocampus, and cerebellum. We validate these ROIs in three datasets using several criteria, including agreement with existing literature and anatomical atlases. Further, we demonstrate that combining these ROIs with established cortical ROIs recapitulates and extends previously described functional network organization. This new set of ROIs is made publicly available for general use, including a full list of MNI coordinates and functional network labels.

Ultrasonic quantification of cerebral perfusion in acute anterior circulation occlusive stroke-A comparative challenge of the refill- and the bolus-kinetics approach.

PurposeTo prospectively evaluate the potential of semi-quantitative evaluation of cerebral perfusion in acute ischemic stroke by comparing two established ultrasound approaches.Materials and methodsConsecutive inclusion of patients with acute occlusion of middle cerebral artery (MCA) confirmed by either magnetic resonance imaging (MRI) or computed tomography (CT) perfusion imaging qualifying for interventional therapy. Comparison of bilateral high mechanical index (MI) bolus-kinetics (HighMiB) and unilateral low MI refill-kinetics (LowMiR) performed before specific treatment.ResultsIn 16/31 patients HighMiB was eligible, in 8/31 patients LowMiR was eligible. In six out of these eight patients both HighMiB and LowMiR were eligible for direct comparison. In MR/CT perfusion imaging of the 16 patients eligible for HighMiB, 29/48 cortical regions of interest (ROIs) (60%) displayed hypoperfusion or ischemia, areas inadequately accessible by LowMiR. These ROIs made up 49% of the 59 ROIs displaying hypoperfusion or ischemia, altogether. Matching of parameters in normal and impaired ROIs between LowMiR and MRI/CT perfusion imaging was significantly poorer than in HighMiB.ConclusionLowMiR using refill-kinetics potentially has the advantage of real time imaging and better resolution. The diagnostic impact, however, proves inferior to HighMiB both with respect to imaging quality and semi-quantitative evaluation.