Biology subjects

Hacker, C. D.

Publications and source records attributed to Hacker, C. D..

3 recordsLinked to original sources

bioRxiv2021

Global cerebrospinal fluid circulation mapping using gold nanoparticle enhanced X-ray microtomography reveals region-specific brain and spinal cord CSF pathways

Cerebrospinal fluid (CSF) movement within the brain interstitium is essential for the development and functioning of the brain. However, the interstitium has largely been thought of as a single entity through which CSF circulates, and it is not known whether specific cell populations within the CNS preferentially interact with CSF. Here, we developed a novel technique for CSF tracking, gold nanoparticle enhanced X-ray microtomography, to achieve micrometer-scale resolution visualization of CSF pathways during development. Using this method and subsequent histological analysis, we map global CSF pathways and present novel particle size-dependent circulation patterns through the CNS. We identify an intraparenchymal CSF circulation that targets stem cell-rich and cholinergic neuronal populations. CSF solute distribution to these areas is mediated by CSF flow along projections from the basal cisterns which is altered in posthemorrhagic hydrocephalus. Our study uncovers region-specific patterns in a biologically driven CSF circulation that has implications for normal brain development and the pathophysiology of hydrocephalus and neurodegenerative disorders.

neuroscience↗

bioRxiv2021

Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression

BackgroundAt the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization. ObjectiveTo identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. MethodsWe used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These "RSNM targets" were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region ("anti-group-mean sgACC targets"). The TBI-D cohort was randomized to receive active (n=9) or sham (n=4) rTMS to RSNM targets. ResultsThe group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were then identified based on DAN anti-correlation and DMN correlation. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was stronger and more reliable for RSNM-derived targets than for "anti-group-mean sgACC targets". Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment led to increased connectivity within and between several relevant regions. ConclusionsRSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.

neuroscience↗

bioRxiv2017

rTMS with individualized resting-state network mapping for neuropsychiatric sequelae of repetitive traumatic brain injury in a retired NFL player

The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial inter-individual variability in anatomical localization of brain networks identified using resting-state functional MRI (rsfMRI). Such variability may be particularly important after repetitive traumatic brain injury (TBI), which is associated with treatment-resistant depression. RSNM enables personalized targeting of repetitive transcranial magnetic stimulation (rTMS), a focal brain stimulation technique that relieves depression when administered over dorsolateral prefrontal cortex.\n\nRSNM was used to identify left/right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and default mode network (DMN) correlations. These targets were spatially distinct from those identified by prior methods. The method was evaluated by administering twenty sessions of left-sided excitatory and right-sided inhibitory rTMS to a retired NFL defensive lineman with progressive treatment-resistant neuropsychiatric disturbances. Treatment led to improvement in Montgomery-Asberg Depression Rating Scale (72%), cognitive testing, and headache scales. In comparison with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with medial temporal lobe (MTL). Serial rsfMRI scans showed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with subgenual anterior cingulate cortex. This highlights the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.

neuroscience↗