Electrical stimulation of cranial nerves in cognition and disease.

The cranial nerves are the pathways through which environmental information (sensation) is directly communicated to the brain, leading to perception, and giving rise to higher cognition. Because cranial nerves determine and modulate brain function, invasive and non-invasive cranial nerve electrical stimulation methods have applications in the clinical, behavioral, and cognitive domains. Among other neuromodulation approaches such as peripheral, transcranial and deep brain stimulation, cranial nerve stimulation is unique in allowing axon pathway-specific engagement of brain circuits, including thalamo-cortical networks. In this review we amalgamate relevant knowledge of 1) cranial nerve anatomy and biophysics; 2) evidence of the modulatory effects of cranial nerves on cognition; 3) clinical and behavioral outcomes of cranial nerve stimulation; and 4) biomarkers of nerve target engagement including physiology, electroencephalography, neuroimaging, and behavioral metrics. Existing non-invasive stimulation methods cannot feasibly activate the axons of only individual cranial nerves. Even with invasive stimulation methods, selective targeting of one nerve fiber type requires nuance since each nerve is composed of functionally distinct axon-types that differentially branch and can anastomose onto other nerves. None-the-less, precisely controlling stimulation parameters can aid in affecting distinct sets of axons, thus supporting specific actions on cognition and behavior. To this end, a rubric for reproducible dose-response stimulation parameters is defined here. Given that afferent cranial nerve axons project directly to the brain, targeting structures (e.g. thalamus, cortex) that are critical nodes in higher order brain networks, potent effects on cognition are plausible. We propose an intervention design framework based on driving cranial nerve pathways in targeted brain circuits, which are in turn linked to specific higher cognitive processes. State-of-the-art current flow models that are used to explain and design cranial-nerve-activating stimulation technology require multi-scale detail that includes: gross anatomy; skull foramina and superficial tissue layers; and precise nerve morphology. Detailed simulations also predict that some non-invasive electrical or magnetic stimulation approaches that do not intend to modulate cranial nerves per se, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), may also modulate activity of specific cranial nerves. Much prior cranial nerve stimulation work was conceptually limited to the production of sensory perception, with individual titration of intensity based on the level of perception and tolerability. However, disregarding sensory emulation allows consideration of temporal stimulation patterns (axon recruitment) that modulate the tone of cortical networks independent of sensory cortices, without necessarily titrating perception. For example, leveraging the role of the thalamus as a gatekeeper for information to the cerebral cortex, preventing or enhancing the passage of specific information depending on the behavioral state. We show that properly parameterized computational models at multiple scales are needed to rationally optimize neuromodulation that target sets of cranial nerves, determining which and how specific brain circuitries are modulated, which can in turn influence cognition in a designed manner.

Can we improve the prevention and detection of congenital abnormalities? An audit of early pregnancy care in New Zealand.

AIM: To determine whether there were "quality gaps" in the provision of care during pregnancies that resulted in a perinatal death due to congenital abnormality. METHOD: Perinatal deaths from congenital cardiovascular, central nervous system or chromosomal abnormality in 2010 were identified retrospectively. Data were extracted by retrospective clinical note review and obtained by independent review of ultrasound scans. RESULTS: There were 137 perinatal deaths due to a congenital cardiovascular (35), central nervous system (29) or chromosomal abnormality (73). First contact with a health professional during pregnancy was predominantly with a general practitioner. First contact occurred within 14 weeks in 85% of pregnancies and there was often a significant delay before booking. Folate supplements were taken by 7% pre-conceptually and 54% of women in the antenatal period. There were 20 perinatal deaths from neural tube defects that could potentially have been prevented through the use of pre-conceptual folate. Antenatal screening was offered to 75% of the women who presented prior to 20 weeks and 84% of these undertook at least one of the available antenatal screening tests. Review of ultrasound images found five abnormalities could have been detected earlier. CONCLUSION: Delay in booking or failure to offer screening early were the most common reasons for delay in diagnosis of screen detectable abnormalities. The preventative value and timing of (pre-conceptual) folate needs emphasis.

Central nervous system manifestations of Q fever responsive to steroids.

We report the clinical and radiological central nervous system manifestations of a 27-year-old man with Q fever who subsequently developed acute disseminated encephalomyelitis and showed a significant response to steroids. The patient presented with headache and fever and quickly progressed to develop acute respiratory failure and hepatitis. A prompt evaluation revealed positive serology for Q fever and doxycycline was initiated. Approximately 1 week into his illness he was noted to be profoundly weak. Neuroimaging with magnetic resonance imaging (MRI) revealed diffuse white matter T2/FLAIR hyperintensities, with evidence of restricted diffusion. He was given high-dose steroids for a presumed diagnosis of acute disseminated encephalomyelitis (ADEM) and within days he had both clinical and MRI improvement. In addition to well-described meningitis and encephalitis, Q fever may also be associated with diffuse CNS lesions that may be demyelinating inflammatory in pathophysiology, and therefore responsive to high-dose steroids.

Brain 18-FDG PET scan in central nervous system langerhans cell histiocytosis.

We used positron emission tomography (PET) to characterize cerebral metabolism in 7 patients (serial examinations in 2 patients) with central nervous system disease in Langerhans cell histiocytosis (CNS-LCH) who had neuroendocrine abnormalities (n = 7), neuropsychiatric disabilities (n = 3), and CNS degenerative disease (n = 1). The PET scan alterations occurred at localizations with known CNS-LCH disease. The PET scans revealed areas where the metabolism and function were altered in 6 of the 7 patients studied, with either an increased or a decreased metabolism (uptake of glucose). Serial examinations may indicate alterations in the degree of ongoing disease activity, but further studies on functional imaging are desired. The additional information of PET compared with MRI is the ability to detect alterations in CNS metabolic activity in certain patients with CNS-LCH. PET may also provide a tool for longitudinal follow-up of therapeutic measures in selected patients.