Transcranial alternating current stimulation improved working memory in the elderly

In 2012, the FDA decided to classify transcranial electrotherapy stimulators, which had been marketed for use in anxiety, depression, and substance abuse, as class 3 devices, requiring special permits for use, because of lack of efficacy. The FDA suggested that poor evidence for efficacy meant that use of the devices would take away from the use of better proven methods of treatment.

Yesterday, Nature Neuroscience published a study showing that alternating current transcranial stimulation increases working memory slightly in elderly adults who do not have dementia, but have a working memory deficit compared to younger adults.

How is the study device different from the alternating current stimulators that were developed 20 years ago and then reclassified as a failure 7 years ago?

One factor is certainly the location of the stimulation. The older devices had electrodes placed lower on the head, intending in theory to stimulate the thalamus. The new devices stimulate the frontal and anterior temporal areas.

Is the device clinically useful? That is not so clear. The military tested direct current cranial stimulators on its pilots about ten years ago and found they could shift skill sets in the pilots from styles favoring quick decisions to styles favoring slower but more accurate decisions. They were not able to successfully increase one type of skill without limiting another. More study will be needed to see if the new technique can help working memory without affecting other parts of cognition negatively.

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ABSTRACT

Article | Published: 08 April 2019

Working memory revived in older adults by synchronizing rhythmic brain circuits

Robert M. G. Reinhart & John A. Nguyen

Nature Neuroscience (2019)

Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here we show a core feature of cognitive decline—working-memory deficits—emerges from disconnected local and long-range circuits instantiated by theta–gamma phase–amplitude coupling in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60–76 years. After 25 min of stimulation, frequency-tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender–receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working-memory performance that outlasted a 50 min post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.

Cacao flower

I planted a baby cacao tree in the shade of two hala trees about 6 years ago. It took many years to finally bloom this year: there is definitely such a thing as too much shade even for cacao.

Thoughts on the Apple Heart Study

The preliminary findings of the Apple watch heart study were announced this weekend: see this link. This study, paid for by Apple and run via the Stanford Medical School, found a 0.5% incidence of previously undiagnosed episodic atrial fibrillation via Apple Watch, a finding which was confirmed with patch type cardiac monitoring in 84 per cent of cases. The Apple Watch algorithm was calculated to have a 71% positive predictive value for intermittent atrial fibrillation.

Atrial fibrillation is a known risk factor for stroke from cerebral embolism. The incidence of stroke in intermittent atrial fibrillation can be reduced by 70% with the use of anticoagulation medication. Thus, finding cases of atrial fibrillation in the general population and considering treating them with anti-coagulation may be of significant value.

One issue that has not yet been decided is whether the population of people with an Apple Watch is comparable to the populations studied when warfarin was found superior to aspirin. Those populations were often in higher risk groups for stroke than wearers of the Apple Watch might be. The incidence of occult atrial fibrillation is thought to be "0.5 per 1,000 person-years before age 50 to 9.7 per 1,000 person-years after age 70." Is treatment then indicated in people in whom consumer electronics shows a rare episode of atrial fibrillation? Or will we find that persons with rare episodes of atrial fibrillation are more common than previously known, and that such persons as a whole do not need anticoagulant treatment, when in some future decade most mass produced clothing will be able to monitor vital signs? Time will tell.

Taste pathways in mice show crossactivation of some taste and some pain pathways.

For the foraging wild mouse, bitter tastes are often alkaloids in food which may be poisonous. So it is not surprising that it may be of value for a mouse to avoid bitter food as if eating it hurt.

What is more intriguing for us humans would be what a similar pathway might mean about the intersection of heat and flavor in hot tasting cuisines.

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ABSTRACT

Mouse Parabrachial Neurons Signal a Relationship between Bitter Taste and Nociceptive Stimuli

Jinrong Li and Christian H. Lemon

Journal of Neuroscience 27 February 2019, 39 (9) 1631-1648; DOI: https://doi.org/10.1523/JNEUROSCI.2000-18.2018

Taste and somatosensation both mediate protective behaviors. Bitter taste guides avoidance of ingestion of toxins while pain sensations, such as noxious heat, signal adverse conditions to ward off harm. Although brain pathways for taste and somatosensation are typically studied independently, prior data suggest that they intersect, potentially reflecting their common protective role. To investigate this, we applied electrophysiologic and optogenetic techniques in anesthetized mice of both sexes to evaluate relationships between oral somatosensory and taste activity in the parabrachial nucleus (PbN), implicated for roles in gustation and pain. Spikes were recorded from taste-active PbN neurons tested with oral delivery of thermal and chemesthetic stimuli, including agonists of nocisensitive transient receptor potential (TRP) ion channels on somatosensory fibers. Gustatory neurons were also tested to follow electrical pulse stimulation of an oral somatosensory region of the spinal trigeminal subnucleus caudalis (Vc), which projects to the PbN. Neurons composed classic taste groups, including sodium, electrolyte, appetitive, or bitter cells. Across groups, most neurons spiked to Vc pulse stimulation, implying that trigeminal projections reach PbN gustatory neurons. Among such cells, a subpopulation responsive to the bitter taste stimuli quinine and cycloheximide, and aversive concentrations of sodium, cofired to agonists of nocisensitive TRP channels, including capsaicin, mustard oil, and noxious heat. Such neurons populated the lateral PbN. Further, nociceptive activity in PbN bitter taste neurons was suppressed during optogenetic-assisted inhibition of the Vc, implying convergent trigeminal input contributed to such activity. Our results reveal a novel role for PbN gustatory cells in cross-system signaling related to protection.

SIGNIFICANCE STATEMENT Prior data suggest that gustatory and trigeminal neural pathways intersect and overlap in the parabrachial area. However, no study has directly examined such overlap and why it may exist. Here we found that parabrachial gustatory neurons can receive afferent projections from trigeminal nuclei and fire to oral nociceptive stimuli that excite somatosensory receptors and fibers. Activation to aversive nociceptive stimuli in gustatory cells was associated with responding to behaviorally avoided bitter tastants. We were further able to show that silencing trigeminal projections inhibited nociceptive activity in parabrachial bitter taste neurons. Our results imply that in the parabrachial area, there is predictable overlap between taste and somatosensory processing related to protective coding and that classically defined taste neurons contribute to this process.

No autism risk with MMR vaccine, again.

Yet another study NOT funded by industry that ONCE AGAIN shows NO increased risk of autism with immunization. In fact, the (non-significant however) risk ratio, 0.93, was in fact in favor of the vaccine PROTECTING against autism by decreasing the risk by 7%.

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ABSTRACT

Published: Ann Intern Med. 2019.

DOI: 10.7326/M18-2101

ORIGINAL RESEARCH |5 MARCH 2019

Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study

Anders Hviid, DrMedSci; Jørgen Vinsløv Hansen, PhD; Morten Frisch, DrMedSci; Mads Melbye, DrMedSci

Background: The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake.

Objective: To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination.

Design: Nationwide cohort study.

Setting: Denmark.

Participants: 657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013.

Measurements:

Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score).

Results:

During 5 025 754 person-years of follow-up, 6517 children were diagnosed with autism (incidence rate, 129.7 per 100,000 person-years). Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02). Similarly, no increased risk for autism after MMR vaccination was consistently observed in subgroups of children defined according to sibling history of autism, autism risk factors (based on a disease risk score) or other childhood vaccinations, or during specified time periods after vaccination.

Limitation:

No individual medical chart review was performed.

Conclusion:

The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination. It adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases.

Gene therapy for deafness

It's not a common cause of deafness, but his looks promising. Perhaps one day we will have gene therapy for many developmental disabilities.

ABSTRACT

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Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model

Omar Akil, Frank Dyka, Charlotte Calvet, Alice Emptoz, Ghizlene Lahlou, Sylvie Nouaille, Jacques Boutet de Monvel, Jean-Pierre Hardelin, William W. Hauswirth, Paul Avan, Christine Petit, Saaid Safieddine, and Lawrence R. Lustig

PNAS published ahead of print February 19, 2019 https://doi.org/10.1073/pnas.1817537116

Contributed by Christine Petit, November 27, 2018 (sent for review October 12, 2018; reviewed by Jonathan Gale and Botond Roska)

Significance

In humans, inner ear development is completed in utero, with hearing onset at ∼20 weeks of gestation. However, genetic forms of congenital deafness are typically diagnosed during the neonatal period. Gene therapy approaches in animal models should therefore be tested after the period of hearing onset, to determine whether they can reverse an existing deafness phenotype. Here, we used a mouse model of DFNB9, a human deafness form accounting for 2–8% of all cases of congenital genetic deafness. We show that local gene therapy in the mutant mice not only prevents deafness when administered to immature hearing organs, but also durably restores hearing when administered at a mature stage, raising hopes for future gene therapy trials in DFNB9 patients.

Local Hawaiian music: Britney Paiva on ukulele

Local ukulele virtuoso Britney Paiva performing in church. The second piece (The Prayer) is very inspiring.