Neurophysiological and Behavioral Responses to Music Therapy in Vegetative and Minimally Conscious States

Assessment of awareness for those with disorders of consciousness is a challenging undertaking, due to the complex presentation of the population. Debate surrounds whether behavioral assessments provide greatest accuracy in diagnosis compared to neuro-imaging methods, and despite developments in both, misdiagnosis rates remain high. Music therapy may be effective in the assessment and rehabilitation with this population due to effects of musical stimuli on arousal, attention, and emotion, irrespective of verbal or motor deficits. However, an evidence base is lacking as to which procedures are most effective. To address this, a neurophysiological and behavioral study was undertaken comparing electroencephalogram (EEG), heart rate variability, respiration, and behavioral responses of 20 healthy subjects with 21 individuals in vegetative or minimally conscious states (VS or MCS). Subjects were presented with live preferred music and improvised music entrained to respiration (procedures typically used in music therapy), recordings of disliked music, white noise, and silence. ANOVA tests indicated a range of significant responses (p ? 0.05) across healthy subjects corresponding to arousal and attention in response to preferred music including concurrent increases in respiration rate with globally enhanced EEG power spectra responses (p = 0.05–0.0001) across frequency bandwidths. Whilst physiological responses were heterogeneous across patient cohorts, significant post hoc EEG amplitude increases for stimuli associated with preferred music were found for frontal midline theta in six VS and four MCS subjects, and frontal alpha in three VS and four MCS subjects (p = 0.05–0.0001). Furthermore, behavioral data showed a significantly increased blink rate for preferred music (p = 0.029) within the VS cohort. Two VS cases are presented with concurrent changes (p ? 0.05) across measures indicative of discriminatory responses to both music therapy procedures. A third MCS case study is presented highlighting how more sensitive selective attention may distinguish MCS from VS. The findings suggest that further investigation is warranted to explore the use of music therapy for prognostic indicators, and its potential to support neuroplasticity in rehabilitation programs

Evaluating Controlled Human Malaria Infection in Kenyan Adults with Varying Degrees of Prior Exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection

Background: Controlled human malaria infection (CHMI) studies are a vital tool to accelerate vaccine and drug development. As CHMI trials are performed in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics (PGD) and immunological responses. However, CHMI studies have not been routinely performed in malaria-endemic countries or used to investigate mechanisms of naturally-acquired immunity (NAI) to Plasmodium falciparum. Methods: We conducted an open-label, randomized CHMI pilot-study using aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) to evaluate safety, infectivity and PGD in Kenyan adults with low to moderate prior exposure to P. falciparum (Pan African Clinical Trial Registry: PACTR20121100033272). Results: All participants developed blood-stage infection confirmed by qPCR. However one volunteer (110) remained asymptomatic and blood-film negative until day 21 post-injection of PfSPZ Challenge. This volunteer had a reduced parasite multiplication rate (PMR) (1.3) in comparison to the other 27 volunteers (median 11.1). A significant correlation was seen between PMR and screening anti-schizont ELISA OD (p=0.044, R=-0.384) but not when volunteer 110 was excluded from the analysis (p=0.112, R=-0.313). Conclusions: PfSPZ Challenge is safe and infectious in malaria-endemic populations and could be used to assess the efficacy of malaria vaccines and drugs in African populations. Whilst our findings are limited by sample size, our pilot study has demonstrated for the first time that NAI may impact on PMR post-CHMI in a detectable fashion, an important finding that should be evaluated in further CHMI studies