Wednesday, August 17, 2022

Alcohol, neuronal plasticity, and mitochondrial trafficking

Hernandez and Kaun provide a nice description of work by Knabbe et al. with summary graphics. Here is the start of their text:
Consumption of alcohol creates a sense of euphoria, reduces inhibition, and increases sociability and impulsivity. The age at which alcohol is first experienced is a key factor contributing to the likelihood to misuse alcohol. However, the impacts of the first experience of alcohol on the molecules in the brain at these key developmental stages are not well understood. Knabbe et al. endeavored to address the neuromolecular alterations resulting from acute alcohol by combining hippocampal proteomics with somatosensory and motor cortex protein, dendrite, axon, and mitochondrial analysis in adolescent mice. Evidence from this array of preparations led to the hypothesis that alcohol disrupted mitochondrial trafficking, and using Drosophila they demonstrated a functional role for mitochondrial trafficking in cue-induced alcohol preference.
The cross-assay and cross-species approach outlined in Knabbe et al. proved to be an effective way of discovering how alcohol hijacks brain mechanisms. Animals from flies to humans maintain functionally consistent neurotransmitter systems, neural circuit mechanisms, and molecular pathways underlying reward.
And here is the abstract from Knabbe et al.:
Alcohol intoxication at early ages is a risk factor for the development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope-labeled mice combined with quantitative mass spectrometry to screen more than 2,000 hippocampal proteins, of which 72 changed synaptic abundance up to twofold after ethanol exposure. Among those were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and ankyrin-G. Based on these candidate proteins, we found acute and lasting molecular, cellular, and behavioral changes following a single intoxication in alcohol-naïve mice. Immunofluorescence analysis revealed a shortening of axon initial segments. Longitudinal two-photon in vivo imaging showed increased synaptic dynamics and mitochondrial trafficking in axons. Knockdown of mitochondrial trafficking in dopaminergic neurons abolished conditioned alcohol preference in Drosophila flies. This study introduces mitochondrial trafficking as a process implicated in reward learning and highlights the potential of high-resolution proteomics to identify cellular mechanisms relevant for addictive behavior.

Monday, August 15, 2022

A systematic review of microdosing - research on low dose psychedelics

I pass on the link to this review by Polito and Liknaitzky. Their abstract:
The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to date, including a set of infrequently cited studies that took place prior to prohibition. Specifically, we reviewed 44 studies published between 1955 and 2021, and summarised reported effects across six categories: mood and mental health; wellbeing and attitude; cognition and creativity; personality; changes in conscious state; and neurobiology and physiology. Studies showed a wide range in risk of bias, depending on design, age, and other study characteristics. Laboratory studies found changes in pain perception, time perception, conscious state, and neurophysiology. Self-report studies found changes in cognitive processing and mental health. We review data related to expectation and placebo effects, but argue that claims that microdosing effects are largely due to expectancy are premature and possibly wrong. In addition, we attempt to clarify definitional inconsistencies in the microdosing literature by providing suggested dose ranges across different substances. Finally, we provide specific design suggestions to facilitate more rigorous future research.

Wednesday, August 10, 2022

Music training enhances auditory and linguistic processing.

From Neves et al.:  


• Systematic review and meta-analysis of neurobehavioral effects of music training. 
• We ask whether music training shapes auditory-perceptual and linguistic skills. 
• Multivariate meta-analytic models are combined with narrative synthesis. 
• Music training has a positive effect on auditory and linguistic processing. 
• Our work informs research on plasticity, transfer, and music-based interventions.
It is often claimed that music training improves auditory and linguistic skills. Results of individual studies are mixed, however, and most evidence is correlational, precluding inferences of causation. Here, we evaluated data from 62 longitudinal studies that examined whether music training programs affect behavioral and brain measures of auditory and linguistic processing (N = 3928). For the behavioral data, a multivariate meta-analysis revealed a small positive effect of music training on both auditory and linguistic measures, regardless of the type of assignment (random vs. non-random), training (instrumental vs. non-instrumental), and control group (active vs. passive). The trim-and-fill method provided suggestive evidence of publication bias, but meta-regression methods (PET-PEESE) did not. For the brain data, a narrative synthesis also documented benefits of music training, namely for measures of auditory processing and for measures of speech and prosody processing. Thus, the available literature provides evidence that music training produces small neurobehavioral enhancements in auditory and linguistic processing, although future studies are needed to confirm that such enhancements are not due to publication bias.

Monday, August 08, 2022

Old hearts learn new tricks

Nusinovich's summary in Science Magazine of work by Lerchenmüller et al.:
Aging-related diseases such as heart failure and other cardiovascular disorders are the leading causes of death in many countries, and they are becoming increasingly common worldwide as the number of older people increases. The ability of the heart to produce new cardiomyocytes decreases with age, which makes it more difficult to repair damage and increases the risk of heart failure. However, a study by Lerchenmüller et al. suggests that exercise may offer some help in this regard even if started late in life. The authors had previously reported that voluntary exercise can stimulate the generation of cardiomyocytes in young adult mouse hearts, and now they have also observed this phenomenon in aged animals.
Here is the results statement of the article:
Cardiomyogenesis was observed at a significantly higher frequency in exercised compared with sedentary aged hearts on the basis of the detection of mononucleated/diploid 15N-thymidine–labeled cardiomyocytes. No mononucleated/diploid 15N-thymidine–labeled cardiomyocyte was detected in sedentary aged mice. The annual rate of mononucleated/diploid 15N-thymidine–labeled cardiomyocytes in aged exercised mice was 2.3% per year. This compares with our previously reported annual rate of 7.5% in young exercised mice and 1.63% in young sedentary mice. Transcriptional profiling of young and aged exercised murine hearts and their sedentary controls revealed that exercise induces pathways related to circadian rhythm, irrespective of age. One known oscillating transcript, however, that was exclusively upregulated in aged exercised hearts, was isoform 1.4 of regulator of calcineurin, whose regulation and functional role were explored further.

Friday, August 05, 2022

Dissecting and improving motor skill acquisition in older adults

 From the introduction of Elvira et al. (open source):

We designed a study intended to identify (i) the main factors leading to differences in motor skill acquisition with aging and (ii) the effect of applying noninvasive brain stimulation during motor training. Comparing different components of motor skill acquisition in young and older adults, constituting the extremes of performance in this study, we found that the improvement of the sequence-tapping task is maximized by the early consolidation of the spatial properties of the sequence in memory (i.e., sequence order), leading to a reduced error of execution, and by the optimization of its temporal features (i.e., chunking). We found the consolidation of spatiotemporal features to occur early in training in young adults, suggesting the emergence of motor chunks to be a direct consequence of committing the sequence elements to memory. This process, seemingly less efficient in older adults, could be partially restored using atDCS by enabling the early consolidation of spatial features, allowing them to prioritize the increase of their speed of execution, ultimately leading to an earlier consolidation of motor chunks. This separate consolidation of spatial and temporal features seen in older adults suggests that the emergence of temporal patterns, commonly identified as motor chunks at a behavioral level, stem from the optimization of the execution of the motor sequence resulting from practice, which can occur only after the sequence order has been stored in memory.
Here is their abstract:
Practicing a previously unknown motor sequence often leads to the consolidation of motor chunks, which enable its accurate execution at increasing speeds. Recent imaging studies suggest the function of these structures to be more related to the encoding, storage, and retrieval of sequences rather than their sole execution. We found that optimal motor skill acquisition prioritizes the storage of the spatial features of the sequence in memory over its rapid execution early in training, as proposed by Hikosaka in 1999. This process, seemingly diminished in older adults, was partially restored by anodal transcranial direct current stimulation over the motor cortex, as shown by a sharp improvement in accuracy and an earlier yet gradual emergence of motor chunks. These results suggest that the emergence of motor chunks is preceded by the storage of the sequence in memory but is not its direct consequence; rather, these structures depend on, and result from, motor practice.

Wednesday, August 03, 2022

Motor learning without movement

Fascinating work from Kim et al. on the influence of the prediction errors that are essential in calibrating actions of our predictive minds:


Our brains control aspects of our movements without conscious awareness, allowing many of us to effortlessly pick up a glass of water or wave hello. Here, we demonstrate that this implicit motor system can learn to refine movements that we plan but ultimately decide not to perform. Participants planned to reach to a target but sometimes withheld these reaches while an animation simulated missing the target. Afterward, participants unknowingly reached opposite the direction of the apparent mistake, indicating that the implicit motor system had learned from the animated error. These findings indicate that movement is not strictly necessary for motor adaptation, and we can learn to update our actions without physically performing them.
Prediction errors guide many forms of learning, providing teaching signals that help us improve our performance. Implicit motor adaptation, for instance, is thought to be driven by sensory prediction errors (SPEs), which occur when the expected and observed consequences of a movement differ. Traditionally, SPE computation is thought to require movement execution. However, recent work suggesting that the brain can generate sensory predictions based on motor imagery or planning alone calls this assumption into question. Here, by measuring implicit motor adaptation during a visuomotor task, we tested whether motor planning and well-timed sensory feedback are sufficient for adaptation. Human participants were cued to reach to a target and were, on a subset of trials, rapidly cued to withhold these movements. Errors displayed both on trials with and without movements induced single-trial adaptation. Learning following trials without movements persisted even when movement trials had never been paired with errors and when the direction of movement and sensory feedback trajectories were decoupled. These observations indicate that the brain can compute errors that drive implicit adaptation without generating overt movements, leading to the adaptation of motor commands that are not overtly produced.

Monday, August 01, 2022

Brain changes, or the absence thereof, associated with mindfulness training.

Richard Davidson and his collaborators (open source, with useful graphics) inject a note of sanity into evaluating widely reported claims of brain changes induced by mindfulness meditation techniques. They note in their introduction:
Findings from a few small studies have permeated popular media with the notion that a few weeks of training in mindfulness-based stress reduction (MBSR) can lead to measurable changes in brain structure and have been cited over 3200 times, combined. However, there is a lack of replication (conceptual or direct) or confirmatory analysis of these findings in a fully randomized trial. Moreover, a recent meta-analysis found that the proportion of high-quality publications in this domain have not improved over time, although there are a growing number of high-quality studies being conducted.
Their abstract:
Studies purporting to show changes in brain structure following the popular, 8-week mindfulness-based stress reduction (MBSR) course are widely referenced despite major methodological limitations. Here, we present findings from a large, combined dataset of two, three-arm randomized controlled trials with active and waitlist (WL) control groups. Meditation-naïve participants (n = 218) completed structural magnetic resonance imaging scans during two visits: baseline and postintervention period. After baseline, participants were randomly assigned to WL (n = 70), an 8-week MBSR program (n = 75), or a validated, matched active control (n = 73). We assessed changes in gray matter volume, gray matter density, and cortical thickness. In the largest and most rigorously controlled study to date, we failed to replicate prior findings and found no evidence that MBSR produced neuroplastic changes compared to either control group, either at the whole-brain level or in regions of interest drawn from prior MBSR studies.