Transport of Prions in the Peripheral Nervous System: Pathways, Cell Types, and Mechanisms.

Prion diseases are transmissible protein misfolding disorders that occur in animals and humans where the endogenous prion protein, PrPC, undergoes a conformational change into self-templating aggregates termed PrPSc. Formation of PrPSc in the central nervous system (CNS) leads to gliosis, spongiosis, and cellular dysfunction that ultimately results in the death of the host. The spread of prions from peripheral inoculation sites to CNS structures occurs through neuroanatomical networks. While it has been established that endogenous PrPC is necessary for prion formation, and that the rate of prion spread is consistent with slow axonal transport, the mechanistic details of PrPSc transport remain elusive. Current research endeavors are primarily focused on the cellular mechanisms of prion transport associated with axons. This includes elucidating specific cell types involved, subcellular machinery, and potential cofactors present during this process.

Numerical working memory alters alpha-beta oscillations and connectivity in the parietal cortices.

Although the neural bases of numerical processing and memory have been extensively studied, much remains to be elucidated concerning the spectral and temporal dynamics surrounding these important cognitive processes. To further this understanding, we employed a novel numerical working memory paradigm in 28 young, healthy adults who underwent magnetoencephalography (MEG). The resulting data were examined in the time-frequency domain prior to image reconstruction using a beamformer. Whole-brain, spectrally-constrained coherence was also employed to determine network connectivity. In response to the numerical task, participants exhibited robust alpha/beta oscillations in the bilateral parietal cortices. Whole-brain statistical comparisons examining the effect of numerical manipulation during memory-item maintenance revealed a difference centered in the right superior parietal cortex, such that oscillatory responses during numerical manipulation were significantly stronger than when no manipulation was necessary. Additionally, there was significantly reduced cortico-cortical coherence between the right and left superior parietal regions during the manipulation compared to the maintenance trials, indicating that these regions were functioning more independently when the numerical information had to be actively processed. In sum, these results support previous studies that have implicated the importance of parietal regions in numerical processing, but also provide new knowledge on the spectral, temporal, and network dynamics that serve this critical cognitive function during active working memory maintenance.

Beta and gamma oscillations index cognitive interference effects across a distributed motor network.

The planning and execution of an efficient motor plan is essential to everyday cognitive function, and relies on oscillatory neural responses in both the beta (14-30 â€‹Hz) and gamma (>30 â€‹Hz) bands. Such motor control requires not only the integration of salient information from the environment, but also the inhibition of irrelevant or distracting inputs that often manifest as forms of cognitive interference. While the effects of cognitive interference on motor neural dynamics has been an area of increasing interest recently, it remains unclear whether different subtypes of interference differentially impact these dynamics. We address this issue using magnetoencephalography and a novel adaptation of the Multi-Source Interference Task, wherein two common subtypes of cognitive interference are each presented in isolation, as well as simultaneously. We find evidence for the subtype-invariant indexing of cognitive interference across a widely distributed set of motor regions oscillating in the beta range, including the bilateral primary motor and posterior parietal cortices. Further, we find that superadditive effects of cognitive interference subtypes on behavior are paralleled by gamma oscillations in the contralateral premotor cortex, and determine that these gamma oscillations also predict the superadditive effects on behavior.

Multielectrode Transcranial Electrical Stimulation of the Left and Right Prefrontal Cortices Differentially Impacts Verbal Working Memory Neural Circuitry.

Recent studies have examined the effects of conventional transcranial direct current stimulation (tDCS) on working memory (WM) performance, but this method has relatively low spatial precision and generally involves a reference electrode that complicates interpretation. Herein, we report a repeated-measures crossover study of 25 healthy adults who underwent multielectrode tDCS of the left dorsolateral prefrontal cortex (DLPFC), right DLPFC, or sham in 3 separate visits. Shortly after each stimulation session, participants performed a verbal WM (VWM) task during magnetoencephalography, and the resulting data were examined in the time-frequency domain and imaged using a beamformer. We found that after left DLPFC stimulation, participants exhibited stronger responses across a network of left-lateralized cortical areas, including the supramarginal gyrus, prefrontal cortex, inferior frontal gyrus, and cuneus, as well as the right hemispheric homologues of these regions. Importantly, these effects were specific to the alpha-band, which has been previously implicated in VWM processing. Although stimulation condition did not significantly affect performance, stepwise regression revealed a relationship between reaction time and response amplitude in the left precuneus and supramarginal gyrus. These findings suggest that multielectrode tDCS targeting the left DLPFC affects the neural dynamics underlying offline VWM processing, including utilization of a more extensive bilateral cortical network.