Influence of Quadrato Motor Training on Salivary proNGF and proBDNF

Previous studies demonstrated exercise-induced modulation of neurotrophins, such as Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Yet, no study that we are aware of has examined their change as a function of different training paradigms. In addition, the understanding of the possible training-induced relationship between NGF and BDNF change is still lacking. Consequently, in the current study we examined the effect of a Walking Training (WT) and of Quadrato Motor Training (QMT) on NGF and BDNF precursors (proNGF and proBDNF). QMT is a specifically structured sensorimotor training that involves sequences of movements based on verbal commands, that was previously reported to improve spatial cognition, reflectivity, creativity as well as emotion regulation and general self-efficacy. In addition, QMT was reported to induce electrophysiological and morphological changes, suggesting stimulation of neuroplasticity processes. In two previous independent studies we reported QMT-induced changes in the salivary proNGF and proBDNF levels. Our present results demonstrate that following 12 weeks of daily QMT practice, proNGF level increases while proBDNF showed no significant change. More importantly, while no correlation between the two neurotrophins prior to training was detectable, there was a significant correlation between change in proNGF and proBDNF levels. Taken together the current results suggest that the two neurotrophins undergo a complex modulation, likely related to the different pathways by which they are produced and regulated. Since variations of these neurotrophins have been previously linked to depression, stress and anxiety, the current study may have practical implications and aid in understanding the possible physiological mechanisms that mediate improved well-being, and the dynamic change of neurotrophins as a result of training

Neuroplasticity of language networks in aphasia: advances, updates, and future challenges

Researchers have sought to understand how language is processed in the brain, how brain damage affects language abilities, and what can be expected during the recovery period since the early 19th century. In this review, we first discuss mechanisms of damage and plasticity in the post-stroke brain, both in the acute and the chronic phase of recovery. We then review factors that are associated with recovery. First, we review organism intrinsic variables such as age, lesion volume and location and structural integrity that influence language recovery. Next, we review organism extrinsic factors such as treatment that influence language recovery. Here, we discuss recent advances in our understanding of language recovery and highlight recent work that emphasizes a network perspective of language recovery. Finally, we propose our interpretation of the principles of neuroplasticity, originally proposed by Kleim and Jones (1) in the context of extant literature in aphasia recovery and rehabilitation. Ultimately, we encourage researchers to propose sophisticated intervention studies that bring us closer to the goal of providing precision treatment for patients with aphasia and a better understanding of the neural mechanisms that underlie successful neuroplasticity.P50 DC012283 - NIDCD NIH HHSPublished versio

Art meets science – empowering stroke patients to regain muscular control through creative graphics technology, psycho-physiology and neuroplasticity.

Treating patients with a cerebrovascular accident or stroke is complicated by severity and site of brain lesion. Muscular control is lost when neural pathways are interrupted or damaged due to embolus, thrombosis or ruptured aneurysm. Return of movement is further hindered by sustained spasticity of muscle groups or inflammation or severance to functionally important neural pathways. Neuro-feedback mechanisms have been explored in the past with some success. A new, improved and innovative method is presented that makes use of psycho-physiology techniques providing immediate visual, auditory and neurological feedback via a fast switching device that relays neuro-muscular movement during rehabilitative tasks and exercises. Visual and auditory signals enable the patient to make use of neurological activity in a purposeful manner, re-directing it to particular tasks. Concentrating on a series of tones elicited via a computer console and by vigilance of changing visual graphics displays allows the patient to accurately control unwanted activity and enables the body to re-learn previously damaged neural circuits. Patients gaining the ability to re-direct and re-route neural pathways have made significant gains in returning function to their leg muscles, particularly to the quadriceps group. These are very often the first groups of muscles to be affected during stroke and make the patient wheelchairbound and often permanently disabled. Occupational and social functioning is affected and quality of life is altered. Patients who are able to re-gain posture and re-learn to walk are empowered and have a better chance of returning to social and occupational settings. Trials in the United Kingdom have shown significant benefits for patients using neuro-feedback. Significant success by these patients has provided researchers with the potential benefits of using neuro-feedback in rehabilitation and increases our scientific and clinical knowledge of neuro-plasticity in even the large muscle groups of the damaged human body. This technology bridges creative artistic graphics technology with thorough evidencebased science

Single prazosin infusion in prelimbic cortex Fosters extinction of amphetamine-induced conditioned place preference

Exposure to drug-associated cues to induce extinction is a useful strategy to contrast cue-induced drug seeking. Norepinephrine (NE) transmission in medial prefrontal cortex has a role in the acquisition and extinction of conditioned place preference induced by amphetamine. We have reported recently that NE in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference (CPP). A potential involvement of α1-adrenergic receptors in the extinction of appetitive conditioned response has been also suggested, although their role in prelimbic cortex has not been yet fully investigated. Here, we investigated the effects of the α1-adrenergic receptor antagonist prazosin infusion in the prelimbic cortex of C57BL/6J mice on expression and extinction of amphetamine-induced CPP. Acute prelimbic prazosin did not affect expression of amphetamine-induced CPP on the day of infusion, while in subsequent days it produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine (Conditioned stimulus, CS). Moreover, prazosin-treated mice that had extinguished CS preference showed increased mRNA expression of brain-derived neurotrophic factor (BDNF) and post-synaptic density 95 (PSD-95) in the nucleus accumbens shell or core, respectively, thus suggesting that prelimbic α1-adrenergic receptor blockade triggers neural adaptations in subcortical areas that could contribute to the extinction of cue-induced drug-seeking behavior. These results show that the pharmacological blockade of α1-adrenergic receptors in prelimbic cortex by a single infusion is able to induce extinction of amphetamine-induced CPP long before control (vehicle) animals, an effect depending on contingent exposure to retrieval, since if infused far from or after reactivation it did not affect preference. Moreover, they suggest strongly that the behavioral effects depend on post-treatment neuroplasticity changes in corticolimbic network, triggered by a possible “priming” effect of prazosin, and point to a potential therapeutic power of the antagonist for maladaptive memories

Signaling pathways linking behavior to neurogenesis in healthy brain and disease

Self-repair of the adult brain is limited – most diseases lack effective therapy. In order to better understand how a regenerative response can be achieved, studying mechanisms shaping the neurogenic niche, from environmental factors to intrinsic signaling, is of significance. My work highlights the enormous plasticity of the CNS and the crucial role of serotonin in affecting the behavior of neural stem/progenitor cells. It allows important insights into antidepressant strategies that involve physical activity, adult neurogenesis, BDNF, and signals of the vascular niche. Future research will have to elucidate the systemic cues and targets that regulate neuroplasticity and how they become deregulated in disease. It remains to be seen how they will contribute to the development of novel therapies and biomarkers for cognitive disorders