Objective

To test the predictive accuracy of the Framingham Risk Score for Stroke (FRS-S) in HIV-infected (HIV+) vs HIV-uninfected (HIV-) men.

Methods

The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of HIV+ and HIV- men who have sex with men (MSM) enrolled in 4 US cities. We ascertained all reported stroke events during a recent 15-year timeframe (July 1, 1996 to June 30, 2011) among 3,945 participants (1,776 HIV+ and 2,169 HIV-). For those with strokes, FRS-S were calculated 10 years before the stroke event and assessed according to HIV status.

Results

A total of 114 stroke events occurred, including 57 HIV+ and 37 HIV- participants with first-ever strokes and 19 fatal strokes. The incidence of first-ever stroke was 1.7/1,000 person-years among HIV- and 3.3/1,000 person-years among HIV+ participants. Among those with strokes, HIV+ participants were younger than HIV- participants (median age 51.3 vs 61.8 years, p < 0.0001). For these men with stroke, the average 10-year risk of stroke was higher for HIV- MSM (6.6% [range 3%-26%] vs 4.9% for HIV+ MSM [range 0%-15%], p < 0.04). Traditional risk factors for stroke were similar among the Framingham cohort and the MACS HIV+ and HIV- participants.

Conclusions

FRS-S prediction was systematically different in HIV+ vs HIV- men with stroke events. The FRS-S underestimates the long-term risk of stroke in HIV+ men.

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology.

Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.

The North American Imaging in Multiple Sclerosis (NAIMS) Cooperative represents a network of 27 academic centers focused on accelerating the pace of magnetic resonance imaging (MRI) research in multiple sclerosis (MS) through idea exchange and collaboration. Recently, NAIMS completed its first project evaluating the feasibility of implementation and reproducibility of quantitative MRI measures derived from scanning a single MS patient using a high-resolution 3T protocol at seven sites. The results showed the feasibility of utilizing advanced quantitative MRI measures in multicenter studies and demonstrated the importance of careful standardization of scanning protocols, central image processing, and strategies to account for inter-site variability.

Objective

To summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings.

Methods

Clinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement.

Results

A wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design.

Conclusions

Imaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials^1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus^5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.