Assessment of [18F]PI-2620 Tau-PET Quantification via Non-Invasive Automatized Image Derived Input Function.

PURPOSE: [18F]PI-2620 positron emission tomography (PET) detects misfolded tau in progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). We questioned the feasibility and value of absolute [18F]PI-2620 PET quantification for assessing tau by regional distribution volumes (VT). Here, arterial input functions (AIF) represent the gold standard, but cannot be applied in routine clinical practice, whereas image-derived input functions (IDIF) represent a non-invasive alternative. We aimed to validate IDIF against AIF and we evaluated the potential to discriminate patients with PSP and AD from healthy controls by non-invasive quantification of [18F] PET. METHODS: In the first part of the study, we validated AIF derived from radial artery whole blood against IDIF by investigating 20 subjects (ten controls and ten patients). IDIF were generated by manual extraction of the carotid artery using the average and the five highest (max5) voxel intensity values and by automated extraction of the carotid artery using the average and the maximum voxel intensity value. In the second part of the study, IDIF quantification using the IDIF with the closest match to the AIF was transferred to group comparison of a large independent cohort of 40 subjects (15 healthy controls, 15 PSP patients and 10 AD patients). We compared VT and VT ratios, both calculated by Logan plots, with distribution volume (DV) ratios using simplified reference tissue modelling and standardized uptake value (SUV) ratios. RESULTS: AIF and IDIF showed highly correlated input curves for all applied IDIF extraction methods (0.78 < r < 0.83, all p < 0.0001; area under the curves (AUC): 0.73 < r ≤ 0.82, all p ≤ 0.0003). Regarding the VT values, correlations were mainly found between those generated by the AIF and by the IDIF methods using the maximum voxel intensity values. Lowest relative differences (RD) were observed by applying the manual method using the five highest voxel intensity values (max5) (AIF vs. IDIF manual, avg: RD = -82%; AIF vs. IDIF automated, avg: RD = -86%; AIF vs. IDIF manual, max5: RD = -6%; AIF vs. IDIF automated, max: RD = -26%). Regional VT values revealed considerable variance at group level, which was strongly reduced upon scaling by the inferior cerebellum. The resulting VT ratio values were adequate to detect group differences between patients with PSP or AD and healthy controls (HC) (PSP target region (globus pallidus): HC vs. PSP vs. AD: 1.18 vs. 1.32 vs. 1.16; AD target region (Braak region I): HC vs. PSP vs. AD: 1.00 vs. 1.00 vs. 1.22). VT ratios and DV ratios outperformed SUV ratios and VT in detecting differences between PSP and healthy controls, whereas all quantification approaches performed similarly in comparing AD and healthy controls. CONCLUSION: Blood-free IDIF is a promising approach for quantification of [18F]PI-2620 PET, serving as correlating surrogate for invasive continuous arterial blood sampling. Regional [18F]PI-2620 VT show large variance, in contrast to regional [18F]PI-2620 VT ratios scaled with the inferior cerebellum, which are appropriate for discriminating PSP, AD and healthy controls. DV ratios obtained by simplified reference tissue modeling are similarly suitable for this purpose.

Development and Preclinical Evaluation of a Copper-64-Labeled Antibody Targeting Glycine-Alanine Dipeptides for PET Imaging of C9orf72-Associated Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.

Aggregating poly(glycine-alanine) (poly-GA) is derived from the unconventional translation of the pathogenic intronic hexanucleotide repeat expansion in the C9orf72 gene, which is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly-GA accumulates predominantly in neuronal cytoplasmic inclusions unique to C9orf72 ALS/FTD patients. Poly-GA is, therefore, a promising target for PET/CT imaging of FTD/ALS to monitor disease progression and therapeutic interventions. A novel 64Cu-labeled anti-GA antibody (mAb1A12) targeting the poly-GA protein was developed and evaluated in a transgenic mouse model. It was obtained with high radiochemical purity (RCP), radiochemical yield (RCY), and specific activity, and showed high stability in vitro and ex vivo and specifically bound to poly-GA. The affinity of NODAGA-mAb1A12 for poly-GA was not affected by this modification. [64Cu]Cu-NODAGA-mAb1A12 was injected into transgenic mice expressing GFP-(GA)175 in excitatory neurons driven by Camk2a-Cre and in control littermates. PET/CT imaging was performed at 2, 20, and 40 h post-injection (p.i.) and revealed a higher accumulation in the cortex in transgenic mice than in wild-type mice, as reflected by higher standardized uptake value ratios (SUVR) using the cerebellum as the reference region. The organs were isolated for biodistribution and ex vivo autoradiography. Autoradiography revealed a higher cortex-to-cerebellum ratio in the transgenic mice than in the controls. Results from autoradiography were validated by immunohistochemistry and poly-GA immunoassays. Moreover, we confirmed antibody uptake in the CNS in a pharmacokinetic study of the perfused tissues. In summary, [64Cu]Cu-NODAGA-mAb1A12 demonstrated favorable in vitro characteristics and an increased relative binding in poly-GA transgenic mice compared to wild-type mice in vivo. Our results with this first-in-class radiotracer suggested that targeting poly-GA is a promising approach for PET/CT imaging in FTD/ALS.

In Vivo Engineering and Transplantation of Axially Vascularized and Epithelialized Flaps in Rats.

The arteriovenous loop (AVL) model allows the in vivo engineering of axially vascularized flaps, the so-called AVL flaps. Although AVL flaps can be transplanted microsurgically to cover tissue defects, they lack an epithelial layer on the surface. Therefore, the objective of this study was to engineer axially vascularized AVL flaps with an accompanying epithelial layer for local defect reconstruction. In this study, AVLs were established in 20 male Lewis rats. Minimally invasive injection of keratinocytes onto the surface of the AVL flaps was performed on postoperative day (POD) 21. AVL flaps were explanted from 12 rats on POD 24 or POD 30, then the epithelium formed by the keratinocytes on the surface of the flaps was evaluated using immunofluorescence staining. In six other rats, the AVL flap was locally transposed to cover a critical defect in the rats' leg on POD 30 and explanted for analysis on POD 40. In two control rats, sodium chloride was applied instead of keratinocytes. These control flaps were also transplanted on POD 30 and explanted on POD 40. Our results revealed that 3 days after keratinocyte application, a loose single-layered epithelium was observed histologically on the AVL flaps surface, whereas after 9 days, a multilayered and structured epithelium had grown. The epithelium on the transplanted AVL flaps showed its physiological differentiation when being exposed to an air-liquid interface. Histologically, a layered epithelium identical to the rats' regular skin was formed. In the sodium chloride control group, no epithelium had been grown. This study clearly demonstrates that axially vascularized AVL flaps can be processed in the subcutaneous chamber by minimally invasive injection of keratinocytes. Thus, AVL flaps with an intact epithelial layer were engineered and could be successfully transplanted for local defect coverage in a small animal model.

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution.

Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach of immunomagnetic cell sorting after in vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect the cellular allocation of PET signals in the TME. In mice with implanted glioblastoma, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs), validated by protein levels. Translation of in vitro scRadiotracing to patients with glioma immediately after tumor resection confirmed higher single-cell TSPO tracer uptake of tumor cells compared to immune cells. Across species, cellular radiotracer uptake explained the heterogeneity of individual TSPO-PET signals. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma; however, proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of PET signals and serves to validate emerging novel TAM-specific radioligands.

Effects of musical mnemonics on working memory performance in cognitively unimpaired older adults and persons with amnestic mild cognitive impairment.

Episodic memory (EM) and working memory (WM) are negatively affected by healthy ageing, and additional memory impairment typically occurs in clinical ageing-related conditions such as amnestic mild cognitive impairment (aMCI). Recent studies on musical mnemonics in Alzheimer's dementia (AD) showed promising results on EM performance. However, the effects of musical mnemonics on WM performance have not yet been studied in (a)MCI or AD. Particularly in (a)MCI the use of musical mnemonics may benefit the optimisation of (working) memory performance. Therefore, in the present study, we examined the effects of musical presentation of digits consisting of pre-recorded rhythms, sung unfamiliar pitch sequences, and their combinations, as compared to spoken presentation. Furthermore, musical expertise was assessed with two perceptual tests and the Self-Report Inventory of the Goldsmiths Musical Sophistication Index. Thirty-two persons with aMCI and 32 cognitively unimpaired older adults (OA) participated in this study. Confirming and extending previous findings in research on ageing, our results show a facilitating effect of rhythm in both cognitively unimpaired OA and persons with aMCI (p = .001, ηp 2 = .158). Furthermore, pitch (p = .048, ηp 2 = .062) and melody (p = .012, ηp 2 = .098) negatively affected performance in both groups. Musical expertise increased this beneficial effect of musical mnemonics (p = .021, ηp 2 = .090). Implications for the future design of music-based memorisation strategies in (a)MCI are discussed.

Motivation and music interventions in adults: A systematic review.

ABSTRACTMusic is increasingly used in a wide array of settings, from clinical recovery to sports or well-being interventions. Motivation related to music is often considered as a possible working mechanism for music to facilitate these processes, however this has not previously been systematically evaluated. The current systematic review considered studies that involved music (therapy) interventions, together with motivation-related measures such as wanting to practise, liking the musical activities, or patient adherence to an intervention. Our objective was to examine whether music is related to increased motivation in task performance and/or rehabilitation settings, and whether this is in turn related to better clinical or training outcomes. Seventy-nine studies met the inclusion criteria, the majority of which (85%) indicated an increased level of motivation with music as compared to without. Moreover, in those studies where motivation was increased, clinical or other outcomes were improved in most cases (90%). These results support the notion of motivation as an underlying mechanism of music-based interventions, but more robust evidence is needed to ascertain which mechanisms are crucial in increasing motivation from a behavioural, cognitive, and neurobiological point of view, as well as how motivational mechanisms relate to other factors of effectiveness in music-based paradigms.

Musical Mnemonics in Cognitively Unimpaired Individuals and Individuals with Alzheimer's Dementia: A Systematic Review.

Based on the idea that music acts as a mnemonic aid, musical mnemonics (i.e., sung presentation of information, also referred to as 'music as a structural prompt'), are being used in educational and therapeutic settings. However, evidence in general and patient populations is still scarce. We investigated whether musical mnemonics affect working and episodic memory performance in cognitively unimpaired individuals and persons with Alzheimer's dementia (AD). Furthermore, we examined the possible contribution of musical expertise. We comprehensively searched the PubMed and PsycINFO databases for studies published between 1970 and 2022. Also, reference lists of all identified papers were manually extracted to identify additional articles. Of 1,126 records identified, 37 were eligible and included. Beneficial effects of musical mnemonics on some aspect of memory performance were reported in 28 of 37 studies, including nine on AD. Nine studies found no beneficial effect. Familiarity contributed positively to this beneficial effect in cognitively unimpaired adults, but require more extensive investigation in AD. Musical expertise generally did not lead to additional benefits for cognitively unimpaired participants, but may benefit people with AD. Musical mnemonics may help to learn and remember verbal information in cognitively unimpaired individuals and individuals with memory impairment. Here, we provide a theoretical model of the possible underlying mechanisms of musical mnemonics, building on previous frameworks. We also discuss the implications for designing music-based mnemonics.

Effects of Musical Mnemonics on Working Memory Performance in Cognitively Unimpaired Young and Older Adults.

OBJECTIVE: To overcome memory decrements in healthy aging, compensation strategies and mnemonics have been found to be promising. The effects of musical mnemonics in aging have been scarcely studied. METHODS: The present study examined the effects of musical presentation of digits (pitch sequences, rhythms, and their combinations) on working memory performance in young and older adults, as compared to spoken presentation. RESULTS: A facilitating effect of rhythm was found in both groups, whereas pitch and melodic cues affected performance negatively in older adults only. Musical training did not moderate the effect of musical mnemonics. DISCUSSION: To investigate whether persons with working memory impairment also benefit from musical mnemonics, follow-up research in older persons with, for instance, mild cognitive impairment or Alzheimer's dementia is recommended.

Individual differences in mental imagery in different modalities and levels of intentionality.

Mental imagery is a highly common component of everyday cognitive functioning. While substantial progress is being made in clarifying this fundamental human function, much is still unclear or unknown. A more comprehensive account of mental imagery aspects would be gained by examining individual differences in age, sex, and background experience in an activity and their association with imagery in different modalities and intentionality levels. The current online study combined multiple imagery self-report measures in a sample (n = 279) with a substantial age range (18-65 years), aiming to identify whether age, sex, or background experience in sports, music, or video games were associated with aspects of imagery in the visual, auditory, or motor stimulus modality and voluntary or involuntary intentionality level. The findings show weak positive associations between age and increased vividness of voluntary auditory imagery and decreased involuntary musical imagery frequency, weak associations between being female and more vivid visual imagery, and relations of greater music and video game experience with higher involuntary musical imagery frequency. Moreover, all imagery stimulus modalities were associated with each other, for both intentionality levels, except involuntary musical imagery frequency, which was only related to higher voluntary auditory imagery vividness. These results replicate previous research but also contribute new insights, showing that individual differences in age, sex, and background experience are associated with various aspects of imagery such as modality, intentionality, vividness, and frequency. The study's findings can inform the growing domain of applications of mental imagery to clinical and pedagogical settings.

Multilevel rhythms in multimodal communication.

It is now widely accepted that the brunt of animal communication is conducted via several modalities, e.g. acoustic and visual, either simultaneously or sequentially. This is a laudable multimodal turn relative to traditional accounts of temporal aspects of animal communication which have focused on a single modality at a time. However, the fields that are currently contributing to the study of multimodal communication are highly varied, and still largely disconnected given their sole focus on a particular level of description or their particular concern with human or non-human animals. Here, we provide an integrative overview of converging findings that show how multimodal processes occurring at neural, bodily, as well as social interactional levels each contribute uniquely to the complex rhythms that characterize communication in human and non-human animals. Though we address findings for each of these levels independently, we conclude that the most important challenge in this field is to identify how processes at these different levels connect. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.

"Help! I Need Somebody": Music as a Global Resource for Obtaining Wellbeing Goals in Times of Crisis.

Music can reduce stress and anxiety, enhance positive mood, and facilitate social bonding. However, little is known about the role of music and related personal or cultural (individualistic vs. collectivistic) variables in maintaining wellbeing during times of stress and social isolation as imposed by the COVID-19 crisis. In an online questionnaire, administered in 11 countries (Argentina, Brazil, China, Colombia, Italy, Mexico, the Netherlands, Norway, Spain, the UK, and USA, N = 5,619), participants rated the relevance of wellbeing goals during the pandemic, and the effectiveness of different activities in obtaining these goals. Music was found to be the most effective activity for three out of five wellbeing goals: enjoyment, venting negative emotions, and self-connection. For diversion, music was equally good as entertainment, while it was second best to create a sense of togetherness, after socialization. This result was evident across different countries and gender, with minor effects of age on specific goals, and a clear effect of the importance of music in people's lives. Cultural effects were generally small and surfaced mainly in the use of music to obtain a sense of togetherness. Interestingly, culture moderated the use of negatively valenced and nostalgic music for those higher in distress.

A Closer Look at a Small Brain: Transnuchal Ultrasound Facilitates High-Resolution Imaging of the Cerebellum in Preterm Infants.

PURPOSE: Very preterm infants are at risk for cerebellar injury and impaired cerebellar growth with adverse neurodevelopmental outcome. Ultrasound through the mastoid fontanel (MF) with a curved-array or sector probe is the most established method for the sonographic examination of the cerebellum. The goal of our study was to examine the validity of transnuchal ultrasound through the foramen occipitale magnum (FOM) with a linear probe for monitoring postnatal cerebellar growth. METHODS: Retrospective analysis of routine ultrasound scans through FOM and MF in 105 preterm infants born between 23 and 36 weeks of gestation with a birthweight of less than 1500 g. RESULTS: Diameters of the cerebellar hemispheres obtained through the two acoustic windows mastoid fontanel and foramen occipitale magnum showed high correlations (r's = 0.981 and 0.983, p's < 0.001). Corrected gestational age was significantly associated with transverse cerebellar diameter (TCD) on the first scan (r = 0.908, p < 0.001) as well as postnatal cerebellar growth (r = 0.920, p < 0.001). Postnatal growth was slightly decreased resulting in cerebellar growth restriction on serial scans. Both associations exceeded the calculated ratio of TCD to head circumference (r = 0.657, p < 0.001) and TCD to biparietal diameter with gestational age (r = 0.705, p < 0.001). CONCLUSION: Transnuchal ultrasound is feasible for examination of the preterm cerebellum and improves image quality compared to scans through the MF with higher resolution at a very short distance. Monitoring cerebellar growth during early postnatal life via transnuchal ultrasound can help to identify children at high risk for neurodevelopmental impairment.

Increased representation of the non-dominant hand in pianists demonstrated by measurement of 3D morphology of the central sulcus.

Background: Post-mortem and magnetic resonance imaging (MRI) studies of the central sulcus, as an indicator of motor cortex, have shown that in the general population there is greater representation of the dominant compared to the non-dominant hand. Studies of musicians, who are highly skilled in performing complex finger movements, have suggested this dominance is affected by musical training, but methods and findings have been mixed. Objective: In the present study, an automated image analysis pipeline using a 3D mesh approach was applied to measure central sulcus (CS) asymmetry on MR images obtained for a cohort of right-handed pianists and matched controls. Methods: The depth, length, and surface area (SA) of the CS and thickness of the cortical mantle adjacent to the CS were measured in each cerebral hemisphere by applying the BrainVISA Morphologist 2012 software pipeline to 3D T1-weighted MR images of the brain obtained for 15 right-handed pianists and 14 controls, matched with respect to age, sex, and handedness. Asymmetry indices (AIs) were calculated for each parameter and multivariate analysis of covariance (MANCOVA), and post hoc tests were performed to compare differences between the pianist and control groups. Results: A one-way MANCOVA across the four AIs, controlling for age and sex, revealed a significant main effect of group (P = 0.04), and post hoc analysis revealed that while SA was significantly greater in the left than the right cerebral hemisphere in controls (P < 0.001), there was no significant difference between left and right SA in the pianists (P = 0.634). Independent samples t-tests revealed that the SA of right CS was significantly larger in pianists compared to controls (P = 0.015), with no between-group differences in left CS. Conclusions: Application of an image analysis pipeline to 3D MR images has provided robust evidence of significantly increased representation of the non-dominant hand in the brain of pianists compared to age-, sex-, and handedness-matched controls. This finding supports prior research showing structural differences in the central sulcus in musicians and is interpreted to reflect the long-term motor training and high skill level of right-handed pianists in using their left hand.

Diffusion tensor MRI tractography reveals increased fractional anisotropy (FA) in arcuate fasciculus following music-cued motor training.

Auditory cues are frequently used to support movement learning and rehabilitation, but the neural basis of this behavioural effect is not yet clear. We investigated the microstructural neuroplasticity effects of adding musical cues to a motor learning task. We hypothesised that music-cued, left-handed motor training would increase fractional anisotropy (FA) in the contralateral arcuate fasciculus, a fibre tract connecting auditory, pre-motor and motor regions. Thirty right-handed participants were assigned to a motor learning condition either with (Music Group) or without (Control Group) musical cues. Participants completed 20minutes of training three times per week over four weeks. Diffusion tensor MRI and probabilistic neighbourhood tractography identified FA, axial (AD) and radial (RD) diffusivity before and after training. Results revealed that FA increased significantly in the right arcuate fasciculus of the Music group only, as hypothesised, with trends for AD to increase and RD to decrease, a pattern of results consistent with activity-dependent increases in myelination. No significant changes were found in the left ipsilateral arcuate fasciculus of either group. This is the first evidence that adding musical cues to movement learning can induce rapid microstructural change in white matter pathways in adults, with potential implications for therapeutic clinical practice.

Intuitive visualizations of pitch and loudness in speech.

Visualizing acoustic features of speech has proven helpful in speech therapy; however, it is as yet unclear how to create intuitive and fitting visualizations. To better understand the mappings from speech sound aspects to visual space, a large web-based experiment (n = 249) was performed to evaluate spatial parameters that may optimally represent pitch and loudness of speech. To this end, five novel animated visualizations were developed and presented in pairwise comparisons, together with a static visualization. Pitch and loudness of speech were each mapped onto either the vertical (y-axis) or the size (z-axis) dimension, or combined (with size indicating loudness and vertical position indicating pitch height) and visualized as an animation along the horizontal dimension (x-axis) over time. The results indicated that firstly, there is a general preference towards the use of the y-axis for both pitch and loudness, with pitch ranking higher than loudness in terms of fit. Secondly, the data suggest that representing both pitch and loudness combined in a single visualization is preferred over visualization in only one dimension. Finally, the z-axis, although not preferred, was evaluated as corresponding better to loudness than to pitch. This relation between sound and visual space has not been reported previously for speech sounds, and elaborates earlier findings on musical material. In addition to elucidating more general mappings between auditory and visual modalities, the findings provide us with a method of visualizing speech that may be helpful in clinical applications such as computerized speech therapy, or other feedback-based learning paradigms.

Motor responses to a steady beat.

It is increasingly well established that music containing an isochronous pulse elicits motor responses at the levels of both brain and behavior. Such motor responses are often used in pedagogical and clinical practice to induce movement, particularly where motor functions are impaired. However, the complex nature of such apparently universal human responses has, arguably, not received adequate research attention to date. In particular, it should be noted that many adults, including those with disabilities, find it somewhat difficult to synchronize their movements with a beat with perfect accuracy; indeed, perfecting the skill of being musically "in time" can take years of training during childhood. Further research is needed on the nature of both the specificity and range of motor responses that can arise from the perception of a steady auditory pulse, with different populations, musical stimuli, conditions, and required levels of accuracy in order to better understand and capture the potential value of the musical beat as a pedagogical and therapeutic tool.

Auditory rhythmic cueing in movement rehabilitation: findings and possible mechanisms.

Moving to music is intuitive and spontaneous, and music is widely used to support movement, most commonly during exercise. Auditory cues are increasingly also used in the rehabilitation of disordered movement, by aligning actions to sounds such as a metronome or music. Here, the effect of rhythmic auditory cueing on movement is discussed and representative findings of cued movement rehabilitation are considered for several movement disorders, specifically post-stroke motor impairment, Parkinson's disease and Huntington's disease. There are multiple explanations for the efficacy of cued movement practice. Potentially relevant, non-mutually exclusive mechanisms include the acceleration of learning; qualitatively different motor learning owing to an auditory context; effects of increased temporal skills through rhythmic practices and motivational aspects of musical rhythm. Further considerations of rehabilitation paradigm efficacy focus on specific movement disorders, intervention methods and complexity of the auditory cues. Although clinical interventions using rhythmic auditory cueing do not show consistently positive results, it is argued that internal mechanisms of temporal prediction and tracking are crucial, and further research may inform rehabilitation practice to increase intervention efficacy.

Moving to music: effects of heard and imagined musical cues on movement-related brain activity.

Music is commonly used to facilitate or support movement, and increasingly used in movement rehabilitation. Additionally, there is some evidence to suggest that music imagery, which is reported to lead to brain signatures similar to music perception, may also assist movement. However, it is not yet known whether either imagined or musical cueing changes the way in which the motor system of the human brain is activated during simple movements. Here, functional magnetic resonance imaging was used to compare neural activity during wrist flexions performed to either heard or imagined music with self-pacing of the same movement without any cueing. Focusing specifically on the motor network of the brain, analyses were performed within a mask of BA4, BA6, the basal ganglia (putamen, caudate, and pallidum), the motor nuclei of the thalamus, and the whole cerebellum. Results revealed that moving to music compared with self-paced movement resulted in significantly increased activation in left cerebellum VI. Moving to imagined music led to significantly more activation in pre-supplementary motor area (pre-SMA) and right globus pallidus, relative to self-paced movement. When the music and imagery cueing conditions were contrasted directly, movements in the music condition showed significantly more activity in left hemisphere cerebellum VII and right hemisphere and vermis of cerebellum IX, while the imagery condition revealed more significant activity in pre-SMA. These results suggest that cueing movement with actual or imagined music impacts upon engagement of motor network regions during the movement, and suggest that heard and imagined cues can modulate movement in subtly different ways. These results may have implications for the applicability of auditory cueing in movement rehabilitation for different patient populations.

Can musical training influence brain connectivity? Evidence from diffusion tensor MRI.

In recent years, musicians have been increasingly recruited to investigate grey and white matter neuroplasticity induced by skill acquisition. The development of Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) has allowed more detailed investigation of white matter connections within the brain, addressing questions about the effect of musical training on connectivity between specific brain regions. Here, current DT-MRI analysis techniques are discussed and the available evidence from DT-MRI studies into differences in white matter architecture between musicians and non-musicians is reviewed. Collectively, the existing literature tends to support the hypothesis that musical training can induce changes in cross-hemispheric connections, with significant differences frequently reported in various regions of the corpus callosum of musicians compared with non-musicians. However, differences found in intra-hemispheric fibres have not always been replicated, while findings regarding the internal capsule and corticospinal tracts appear to be contradictory. There is also recent evidence to suggest that variances in white matter structure in non-musicians may correlate with their ability to learn musical skills, offering an alternative explanation for the structural differences observed between musicians and non-musicians. Considering the inconsistencies in the current literature, possible reasons for conflicting results are offered, along with suggestions for future research in this area.