The Next 50 Years of Neuroscience.

On the 50th anniversary of the Society for Neuroscience, we reflect on the remarkable progress that the field has made in understanding the nervous system, and look forward to the contributions of the next 50 years. We predict a substantial acceleration of our understanding of the nervous system that will drive the development of new therapeutic strategies to treat diseases over the course of the next five decades. We also see neuroscience at the nexus of many societal topics beyond medicine, including education, consumerism, and the justice system. In combination, advances made by basic, translational, and clinical neuroscience research in the next 50 years have great potential for lasting improvements in human health, the economy, and society.

Off-Target drug effects resulting in altered gene expression events with epigenetic and "Quasi-Epigenetic" origins.

This review synthesizes examples of pharmacological agents who have off-target effects of an epigenetic nature. We expand upon the paradigm of epigenetics to include "quasi-epigenetic" mechanisms. Quasi-epigenetics includes mechanisms of drugs acting upstream of epigenetic machinery or may themselves impact transcription factor regulation on a more global scale. We explore these avenues with four examples of conventional pharmaceuticals and their unintended, but not necessarily adverse, biological effects. The quasi-epigenetic drugs identified in this review include the use of beta-lactam antibiotics to alter glutamate receptor activity and the action of cyclosporine on multiple transcription factors. In addition, we report on more canonical epigenome changes associated with pharmacological agents such as lithium impacting autophagy of aberrant proteins, and opioid drugs whose chronic use increases the expression of genes associated with addictive phenotypes. By expanding our appreciation of transcriptomic regulation and the effects these drugs have on the epigenome, it is possible to enhance therapeutic applications by exploiting off-target effects and even repurposing established pharmaceuticals. That is, exploration of "pharmacoepigenetic" mechanisms can expand the breadth of the useful activity of a drug beyond the traditional drug targets such as receptors and enzymes.

Differences in motor inhibition in young and older musicians and non-musicians at rest.

Introduction: Older adults experience a decline in motor inhibition. These declines have been implicated in instrumental activities of daily living. However, studies have revealed that older musicians have behavioral and neurophysiological enhancements in various motor domains compared to non-musicians. This suggests that music training may delay the decline in motor inhibition with aging. Nevertheless, motor inhibition has not been studied in young or older musicians and non-musicians. Thus, the present study aimed to investigate the neurophysiological differences in motor inhibition in aging musicians and non-musicians. Methods: A total of 19 healthy young adult musicians, 16 healthy young non-musicians, 13 healthy older adult musicians, and 16 healthy older adult non-musicians were recruited for the study. Transcranial magnetic stimulation single-pulse (SP) and short interval cortical inhibition (SICI) were performed at rest and then converted into inhibition percentage. Results: We did not observe significant differences between young and older musicians and non-musicians in resting SP MEP. Older adults had lower resting SICI MEP than young adults. Older adults (36%) had a greater percentage of inhibition than young adults (16%). However, when controlling for background EMG activity, musicians had a lower inhibition percentage than non-musicians. Discussion: The results revealed that, despite the greater use of spinal mechanisms, decreased SICI, and increased inhibition percentage in older adults, motor inhibitory circuitry remains intact and functional in both young and older musicians and non-musicians. Future studies will reveal whether there are differences in motor inhibition during movement in musicians across a person's lifespan.

Finger tapping to different styles of music and changes in cortical oscillations.

Music has been a therapeutic strategy proposed to improve impaired movement performance, but there remains a lack of understanding of how music impacts motor cortical activity. Thus, the purpose of this study is to use a time-frequency analysis (i.e., wavelet) of electroencephalographic (EEG) data to determine differences in motor and auditory cortical activity when moving to music at two different rates. Twenty healthy young adults tapped their index finger while electroencephalography was collected. There were three conditions (tapping in time with a tone and with two contrasting music styles), and each condition was repeated at two different rates (70 and 140 beats per minute). A time-frequency Morlet wavelet analysis was completed for electrodes of interest over the sensorimotor areas (FC3, FC4, FCz, C3, C4, Cz) and the primary auditory areas (T7, T8). Cluster-based permutation testing was applied to the electrodes of interest for all conditions. Results showed few differences between cortical oscillations when moving to music versus a tone. However, the two music conditions elicited a variety of distinct responses, particularly at the slower movement rate. These results suggest that music style and movement rate should be considered when designing therapeutic applications that include music to target motor performance.

Music Form but Not Music Experience Modulates Motor Cortical Activity in Response to Novel Music.

External cues, such as music, improve movement performance in persons with Parkinson's disease. However, research examining the motor cortical mechanisms by which this occurs is lacking. Research using electroencephalography in healthy young adults has revealed that moving to music can modulate motor cortical activity. Moreover, motor cortical activity is further influenced by music experience. It remains unknown whether these effects extend to corticomotor excitability. Therefore, the primary aim of this study was to determine the effects of novel music on corticomotor excitability using transcranial magnetic stimulation (TMS) in a pilot study of healthy young adults. A secondary aim of this study was to determine the influence of music experience on corticomotor excitability. We hypothesized that corticomotor excitability will change during music conditions, and that it will differ in those with formal music training. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous using single-pulse TMS in three conditions: (1) No Music, (2) Music Condition I, and (3) Music Condition II. Both pieces were set to novel MIDI piano instrumentation and part-writing conventions typical of early nineteenth-century Western classical practices. Results revealed Music Condition II (i.e., more relaxing music) compared to rest increased MEP amplitude (i.e., corticomotor excitability). Music Condition II as compared to Music Condition I (i.e., more activating music) reduced MEP variability (i.e., corticomotor variability). Finally, years of formal music training did not significantly influence corticomotor excitability while listening to music. Overall, results revealed that unfamiliar music modulates motor cortical excitability but is dependent upon the form of music and possibly music preference. These results will be used to inform planned studies in healthy older adults and people with Parkinson's disease.

The influence of moving with music on motor cortical activity.

Although there is a growing interest in using music to improve movement performance in various populations, there remains a need to better understand how music influences motor cortical activity. Listening to music is tightly linked to neural processes within the motor cortex and can modulate motor cortical activity in healthy young adult (HYAs). There is limited evidence regarding how moving to music modulates motor cortical activity. Thus, the purpose of this study was to explore the influence of moving to music on motor cortical activity in HYAs. Electroencephalography was collected while 32 HYAs tapped their index finger in time with a tone and with two contrasting music styles. Two movement rates were presented for each condition. Power spectra were obtained from data collected over the primary sensorimotor region and supplemental motor area and were compared between conditions. Results revealed a significant difference between both music conditions and the tone only condition for both the regions. For both music styles, power was increased in the beta band for low movement rates and increased in the alpha band for high movement rates. A secondary analysis determining the effect of music experience on motor cortical activity revealed a significant difference between musicians and non-musicians. Power in the beta band was increased across all conditions. The results of this study provide the initial step towards a more complete understanding of the neurophysiological underpinnings of music on movement performance which may inform future studies and therapeutic strategies.