The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus in 81 participants ranging in age from 24 to 76 including 59 HIV+ individuals and 22 HIV‐seronegative controls. T1‐weighted MRI underwent a preprocessing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum, and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus, and thalamus. Of greatest interest, an age × HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age × HIV interaction. These findings may suggest that age and HIV infection conferred additional deleterious effects on subcortical shape abnormalities beyond the independent effects of these factors. Hum Brain Mapp 38:1025–1037, 2017. © 2016 Wiley Periodicals, Inc.     

Vascular health risks and fMRI activation during a memory task in older adults

Vascular problems increase Alzheimer's disease (AD) risk, but the nature of this relationship remains unclear. Older adults having genetic risk for AD show regionally increased functional magnetic resonance imaging (fMRI) activity during memory, possibly representing compensation for a genetically induced neural deficit. We investigated whether vascular health risks, which similarly could lead to neuropsychological deficits, also showed increased fMRI activity during a memory task performed by 30 cognitively intact, primarily normotensive older adults (mean age=61). Vascular risk measures included systolic blood pressure (sBP), body mass index (BMI), and total cholesterol. Higher sBP and BMI (but not total cholesterol) were significantly correlated with increased activation in posterior cingulate cortex and frontal, temporal, and parietal regions. In posterior cingulate and parietal cortices, these relationships were evident even within sBP and BMI ranges considered normal, and were independent of hippocampal volume. Our results are similar to those in prior AD risk research, and suggest that fMRI reveals an abnormal response to cognitive processes in cognitively intact older adults with increased vascular risk.     

Intrinsic network connectivity and own body perception in gender dysphoria

Gender dysphoria (GD) is characterized by incongruence between one’s identity and gender assigned at birth. The biological mechanisms of GD are unclear. We investigated brain network connectivity patterns involved in own body perception in the context of self in GD. Twenty-seven female-to-male (FtM) individuals with GD, 27 male controls, and 27 female controls underwent resting state fMRI. We compared functional connections within intrinsic connectivity networks involved in self-referential processes and own body perception –default mode network (DMN) and salience network – and visual networks, using independent components analyses. Behavioral correlates of network connectivity were also tested using self-perception ratings while viewing own body images morphed to their sex assigned at birth, and to the sex of their gender identity. FtM exhibited decreased connectivity of anterior and posterior cingulate and precuneus within the DMN compared with controls. In FtM, higher “self” ratings for bodies morphed towards the sex of their gender identity were associated with greater connectivity of the anterior cingulate within the DMN, during long viewing times. In controls, higher ratings for bodies morphed towards their gender assigned at birth were associated with right insula connectivity within the salience network, during short viewing times. Within visual networks FtM showed weaker connectivity in occipital and temporal regions. Results suggest disconnectivity within networks involved in own body perception in the context of self in GD. Moreover, perception of bodies in relation to self may be reflective rather than reflexive, as a function of mesial prefrontal processes. These may represent neurobiological correlates to the subjective disconnection between perception of body and self-identification.     

Perceived loss of memory ability and cerebral metabolic decline in persons with the apolipoprotein E-IV genetic risk for Alzheimer disease

CONTEXT: Concerns about age-related memory loss are greater in persons who have the apolipoprotein E-IV (APOE4) genetic risk for Alzheimer disease, but the correlation between the degree of concerns and future cerebral metabolic decline is unknown. OBJECTIVE: To investigate whether the degree of self-perceived memory loss is associated with regional cerebral metabolic decline. DESIGN: Longitudinal study. SETTING: Aging and Memory Research Center, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles. PARTICIPANTS: Thirty right-handed, cognitively intact, middle-aged and older adults (age range, 50-82 years) with age-associated memory complaints, 14 of whom were carriers of the apolipoprotein E-IV allele, were recruited for longitudinal study. MAIN OUTCOME MEASURES: At baseline, we administered a standardized neuropsychological battery and assessed self-appraisal of memory functioning using the Memory Functioning Questionnaire, which yields 4 factor scores indicating frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use. Regional cerebral glucose metabolism was determined using fluorodeoxyglucose F18-positron emission tomography at baseline and after 2 years. RESULTS: At baseline, APOE4 carriers and noncarriers did not differ significantly on objective memory measures or on Memory Functioning Questionnaire factor scores. However, the factor score for frequency of forgetting significantly correlated with global cerebral metabolic decline in all subjects regardless of APOE4 genetic risk (P = .01). By contrast, the factor score for mnemonics use significantly correlated with metabolic decline in the temporal regions in APOE4 carriers but not in noncarriers (P = .03). CONCLUSIONS: The degree of perceived memory loss correlates with subsequent global cerebral metabolic decline for APOE4 carriers and noncarriers; hence, memory complaints may reflect underlying cerebral metabolic changes. Compensatory strategies, as reflected by more frequent mnemonics use in APOE4 carriers, may reflect underlying metabolic changes in the brain regions associated with prodromal Alzheimer disease. Self-reported mnemonics use may be helpful in identifying persons for clinical monitoring.     

Altered functional connectivity of the default mode network in diffuse gliomas measured with pseudo-resting state fMRI

The purpose of the current study was to explore whether brain tumors disrupt the integrity of the default mode network (DMN), a well-characterized resting-state fMRI network. We evaluated whether tumor grade, volume, post-surgical/clinical status, or location decreased the functional connectivity within the DMN in patients with gliomas. Task-based fMRI data was obtained from 68 diffuse glioma patients and 12 healthy volunteers. Pseudo-resting state fMRI data was calculated from task-based fMRI data using standard techniques. Data was preprocessed and DMN integrity was compared across WHO grade, tumor volume surgical status (new vs. recurrent tumors), age, and KPS using univariate and multivariate linear models. WHO grade was the most significant predictor of DMN integrity (P = 0.004), whereas T2 hyperintense lesion volume was not a predictor (P = 0.154). DMN integrity was lower in high-grade (WHO III–IV) compared with low-grade (WHO II) patients (P = 0.020). Tumors in the left parietal lobe showed a more impaired DMN compared with tumors in the frontal lobe, while tumors within and outside the network nodes did not differ significantly. Results suggest higher tumor grade along with prior surgery and/or treatment cause the largest reduction in DMN functional connectivity in patients with primary gliomas, and that tumor location has an impact on connectivity.     

Gray matter loss correlates with mesial temporal lobe neuronal hyperexcitability inside the human seizure-onset zone

Purpose: Patient studies have not provided consistent evidence for interictal neuronal hyperexcitability inside the seizure‐onset zone (SOZ). We hypothesized that gray matter (GM) loss could have important effects on neuronal firing, and quantifying these effects would reveal significant differences in neuronal firing inside versus outside the SOZ. Methods: Magnetic resonance imaging (MRI) and computational unfolding of mesial temporal lobe (MTL) subregions was used to construct anatomic maps to compute GM loss in presurgical patients with medically intractable focal seizures in relation to controls. In patients, these same maps were used to locate the position of microelectrodes that recorded interictal neuronal activity. Single neuron firing and burst rates were evaluated in relation to GM loss and MTL subregions inside and outside the SOZ. Key Findings: MTL GM thickness was reduced inside and outside the SOZ in patients with respect to controls, yet GM loss was associated more strongly with firing and burst rates in several MTL subregions inside the SOZ. Adjusting single neuron firing and burst rates for the effects of GM loss revealed significantly higher firing rates in the subregion consisting of dentate gyrus and CA2 and CA3 (CA23DG), as well as CA1 and entorhinal cortex (EC) inside versus outside the SOZ where normalized MRI GM loss was ≥1.40 mm. Firing rates were higher in subicular cortex inside the SOZ at GM loss ≥1.97 mm, whereas burst rates were higher in CA23DG, CA1, and EC inside than outside the SOZ at similar levels of GM loss. Significance: The correlation between GM loss and increased firing and burst rates suggests GM structural alterations in MTL subregions are associated with interictal neuronal hyperexcitability inside the SOZ. Significant differences in firing rates and bursting in areas with GM loss inside compared to outside the SOZ indicate that synaptic reorganization following cell loss could be associated with varying degrees of epileptogenicity in patients with intractable focal seizures.     

High-definition imaging of trabeculectomy blebs using spectral domain optical coherence tomography adapted for the anterior segment

Background:  The aim of this work was to image trabeculectomy blebs using spectral domain optical coherence tomography (SDOCT).
Methods:  In this prospective cross-sectional study, patients who had undergone trabeculectomy with at least 3 months of follow up were included. Blebs were imaged using an adapted SDOCT system (Cirrus HD-OCT, Carl Zeiss Meditec Inc., Dublin, CA, USA) and time domain anterior segment optical coherence tomography (ASOCT) (Visante OCT, Carl Zeiss Meditec Inc.). An observer masked to clinical data assessed the utility of SDOCT and ASOCT in visualizing structures in successful and failed blebs.
Results:  Fifty-one eyes were imaged, of which 43 (84.3%) were successful. SDOCT showed wall thickening (93.0% vs. 67.4%, P  = 0.006) and discrete hyporeflective spaces in the wall (88.4% vs. 14.0%, P  < 0.0001) in a greater proportion of successful blebs than ASOCT. SDOCT showed the bleb cavity (23.3% vs. 48.8%, P  = 0.02), scleral flap (34.9% vs. 90.7%, P  < 0.0001), subflap space (20.9% vs . 72.1%, P  < 0.0001) and ostium (9.3% vs. 88.4%, P  < 0.0001) in fewer successful blebs than ASOCT. The internal ostium was not visualized in any failed bleb using SDOCT, whereas ASOCT showed the ostium in 87.5% of failed blebs ( P  = 0.001). SDOCT showed cystic spaces in the bleb wall in a greater proportion of successful blebs than failed blebs (88.4% vs. 37.5%, P  = 0.005).
Conclusions:  SDOCT imaging was able to show fine superficial features in the bleb wall. However, SDOCT had limited clinical utility in that it did not provide useful information about deep features such as flap position, bleb cavity formation or patency of the subflap space and internal ostium.