Neural Substrates Associated With Fatigue Symptom In Fibromyalgia

Many patients with fibromyalgia (FM) experience fatigue, but the associated biological mechanisms have not been delineated. We aimed to investigate the neural signatures associated with fatigue severity in patients with FM using MRI. We consecutively recruited 138 patients with FM and collected their clinical profiles and brain-MRI data. We categorized the patients into 3 groups based on their fatigue severity. Using voxel-based morphometry analysis and trend analysis, we first identified neural structures showing volumetric changes associated with fatigue severity, and further explored their seed-to-voxel structural covariance networks (SCNs). Results showed decreased bilateral thalamic volumes were associated with higher severity of fatigue. There was a more widespread distribution of the thalamic SCNs to the frontal, parietal, subcortical, and limbic regions in patients with higher fatigue severity. In addition, increased right inferior temporal cortex volumes were associated with higher severity of fatigue. The right inferior temporal seed showed more SCNs distributions over the temporal cortex and a higher strength of SCNs to the bilateral occipital cortex in patients with higher fatigue severity. The thalamus and the right inferior temporal cortex as well as their altered interactions with cortical and subcortical regions comprise the neural signatures of fatigue in FM.

A neuronal prospect theory model in the brain reward circuitry

Prospect theory, arguably the most prominent theory of choice, is an obvious candidate for neural valuation models. How the activity of individual neurons, a possible computational unit, reflects prospect theory remains unknown. Here, we show with theoretical accuracy equivalent to that of human neuroimaging studies that single-neuron activity in four core reward-related cortical and subcortical regions represents the subjective valuation of risky gambles in monkeys. The activity of individual neurons in monkeys passively viewing a lottery reflects the desirability of probabilistic rewards, parameterized as a multiplicative combination of a utility and probability weighting functions in the prospect theory framework. The diverse patterns of valuation signals were not localized but distributed throughout most parts of the reward circuitry. A network model aggregating these signals reliably reconstructed risk preferences and subjective probability perceptions revealed by the animals' choices. Thus, distributed neural coding explains the computation of subjective valuations under risk.

A Computational Modeling Study to Investigate the Use of Epicranial Electrodes to Deliver Interferential Stimulation to Subcortical Regions

Background: Epicranial cortical stimulation (ECS) is a minimally invasive neuromodulation technique that works by passing electric current between subcutaneous electrodes positioned on the skull. ECS causes a stronger and more focused electric field in the cortex compared to transcranial electric stimulation (TES) where the electrodes are placed on the scalp. However, it is unknown if ECS can target deeper regions where the electric fields become relatively weak and broad. Recently, interferential stimulation (IF) using scalp electrodes has been proposed as a novel technique to target subcortical regions. During IF, two high, but slightly different, frequencies are applied which sum to generate a low frequency field (i.e., 10 Hz) at a target subcortical region. We hypothesized that IF using ECS electrodes would cause stronger and more focused subcortical stimulation than that using TES electrodes.Objective: Use computational modeling to determine if interferential stimulation-epicranial cortical stimulation (IF-ECS) can target subcortical regions. Then, compare the focality and field strength of IF-ECS to that of interferential Stimulation-transcranial electric stimulation (IF-TES) in the same subcortical region.Methods: A human head computational model was developed with 19 TES and 19 ECS disk electrodes positioned on a 10–20 system. After tetrahedral mesh generation the model was imported to COMSOL where the electric field distribution was calculated for each electrode separately. Then in MATLAB, subcortical targets were defined and the optimal configurations were calculated for both the TES and ECS electrodes.Results: Interferential stimulation using ECS electrodes can deliver stronger and more focused electric fields to subcortical regions than IF using TES electrodes.Conclusion: Interferential stimulation combined with ECS is a promising approach for delivering subcortical stimulation without the need for a craniotomy.

Biological Aging, Mortality, and Alzheimer’s Disease Related Biomarkers from Midlife to Old Age

People age at different rates and in different biological systems that may differentially contribute to accelerated decline. Better understanding of biological aging may contribute to identification of better targets for intervention. In 1005 VETSA participants we created 3 indicators of biological age: physiological age (PA), frailty, and brain age. PA included hemoglobin, glucose, lipids, height, weight, waist, systolic and diastolic blood pressure, and age. PA was calculated using the Klemera and Doubal (2006) method. The frailty index summed 37 health deficits (Jiang et al. 2017). A machine learning algorithm was used to estimate brain age across cortical and subcortical regions (Liem et al, 2017); predicted brain age subtracted from chronological age comprised the predicted brain age difference score (PBAD). Frailty and PBAD were calculated at waves 1, 2 and 3 when participants were average age 56, 62, and 68, respectively. PA markers were only available at waves 2 and 3. Outcome measures included mortality by wave 3 and scores on AD-related plasma biomarkers—Neurofilament light (NFL), Tau, and AB40 and AB42 at wave 3. Frailty at wave 1 and 2 predicted mortality. Frailty at wave 1 was significantly associated with wave 3 NFL, AB42 and AB40. Wave 2 & 3 frailty was associated with all biomarkers. Neither PA nor PBAD predicted biomarkers or mortality. The results are striking given the relatively young age of the sample. Even as early as one’s 50s, frailty in a community-dwelling sample predicted accelerated decline and mortality when the outcome age was only 66-73.

White Matter Hyperintensities and Cerebral Microbleeds in Ataxia-Telangiectasia

Background and ObjectivesTo systematically assess the occurrence of cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs) in the largest published cohort of adults with ataxia-telangiectasia (AT).MethodsWe assessed 38 adults with AT (age range 18–55 years) including 15 classic and 23 variant AT, evaluated by two independent assessors. WMHs were quantified on T2-fluid attenuated inversion recovery images using the semiquantitative modified Scheltens and Fazekas scales and CMB on susceptibility-weighted imaging and T2*-weighted gradient echo sequences using the Brain Observer MicroBleed Scale.ResultsCMBs were more frequently found in classic AT compared with variant AT (66.7% vs 5.9%) predominantly in cortical and subcortical regions. WMHs were seen in 25 (73.5%) probands and CMBs in 9 (31.0%). The burden of WMHs increased with age, and WMHs were focused in periventricular and deep white matter regions. WMHs were more frequently seen in variant than classic AT.DiscussionThis cohort study confirms that WMHs and CMBs are a frequent finding in AT. Further longitudinal studies are required to understand how WMHs and CMBs relate to the neurodegeneration that occurs in AT and the predisposition to cerebral hemorrhage.

High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T1-weighted images. We also derived subcortical template SC21 from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats.

Ancient visual channels have a causal role in arithmetic calculations

Humans exhibit complex arithmetic skills, often attributed to our exceptionally large neocortex. However, the past decade has provided ample evidence that the functional domain of the subcortex extends well beyond basic functions. Using a sensitive behavioral method, for the first time, we explored the contributions of lower-order visual monocular channels to symbolic arithmetic operations, addition and subtraction. The pattern of results from 4 different experiments provides converging evidence for a causal relation between mental arithmetic and primitive subcortical regions. The results have major implications for our understanding of the neuroevolutionary development of general numerical abilities–subcortical regions, which are shared across different species, are essential to complex numerical operations. In a bigger conceptual framework, these findings and others call for a shift from the modal view of the exclusive role of the neocortex in high-level cognition to a view that emphasizes the interplay between subcortical and cortical brain networks.

Reduced Regional Cerebral Blood Flow Measured by 99mTc-Hexamethyl Propylene Amine Oxime Single-Photon Emission Computed Tomography in Microgravity Simulated by 5-Day Dry Immersion

Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF. Around 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n=9) or cuffs (n=9) group. rCBF was measured 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, puncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, puncorr<0.001), bilateral insula (right insula peak level: 4.10, puncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, puncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.