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Fulltext Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial

Conlon B, Hamilton C, Meade E, Leong SL, O Connor C, Langguth B, et al.

Sci Rep, 2022 Jun 30;12(1):10845.
PMID: 35773272 DOI: 10.1038/s41598-022-13875-x

More than 10% of the population suffers from tinnitus, which is a phantom auditory condition that is coded within the brain. A new neuromodulation approach to treat tinnitus has emerged that combines sound with electrical stimulation of somatosensory pathways, supported by multiple animal studies demonstrating that bimodal stimulation can elicit extensive neural plasticity within the auditory brain. More recently, in a large-scale clinical trial, bimodal neuromodulation combining sound and tongue stimulation drove significant reductions in tinnitus symptom severity during the first 6 weeks of treatment, followed by diminishing improvements during the second 6 weeks of treatment. The primary objective of the large-scale randomized and double-blinded study presented in this paper was to determine if background wideband noise as used in the previous clinical trial was necessary for bimodal treatment efficacy. An additional objective was to determine if adjusting the parameter settings after 6 weeks of treatment could overcome treatment habituation effects observed in the previous study. The primary endpoint at 6-weeks involved within-arm and between-arm comparisons for two treatment arms with different bimodal neuromodulation settings based on two widely used and validated outcome instruments, Tinnitus Handicap Inventory and Tinnitus Functional Index. Both treatment arms exhibited a statistically significant reduction in tinnitus symptoms during the first 6-weeks, which was further reduced significantly during the second 6-weeks by changing the parameter settings (Cohen's d effect size for full treatment period per arm and outcome measure ranged from - 0.7 to - 1.4). There were no significant differences between arms, in which tongue stimulation combined with only pure tones and without background wideband noise was sufficient to reduce tinnitus symptoms. These therapeutic effects were sustained up to 12 months after the treatment ended. The study included two additional exploratory arms, including one arm that presented only sound stimuli during the first 6 weeks of treatment and bimodal stimulation in the second 6 weeks of treatment. This arm revealed the criticality of combining tongue stimulation with sound for treatment efficacy. Overall, there were no treatment-related serious adverse events and a high compliance rate (83.8%) with 70.3% of participants indicating benefit. The discovery that adjusting stimulation parameters overcomes previously observed treatment habituation can be used to drive greater therapeutic effects and opens up new opportunities for optimizing stimuli and enhancing clinical outcomes for tinnitus patients with bimodal neuromodulation.

Matched MeSH terms: Neuronal Plasticity/physiology
Fulltext Recent Advances on the Role of Brain-Derived Neurotrophic Factor (BDNF) in Neurodegenerative Diseases

Azman KF, Zakaria R

Int J Mol Sci, 2022 Jun 19;23(12).
PMID: 35743271 DOI: 10.3390/ijms23126827

Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are essential for neuronal survival and growth. The signaling cascades initiated by BDNF and its receptor are the key regulators of synaptic plasticity, which plays important role in learning and memory formation. Changes in BDNF levels and signaling pathways have been identified in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, and have been linked with the symptoms and course of these diseases. This review summarizes the current understanding of the role of BDNF in several neurodegenerative diseases, as well as the underlying molecular mechanism. The therapeutic potential of BDNF treatment is also discussed, in the hope of discovering new avenues for the treatment of neurodegenerative diseases.

Matched MeSH terms: Neuronal Plasticity/physiology
Associable representations as field of influence for dynamic cognitive processes

Cacha LA, Poznanski RR

J Integr Neurosci, 2011 Dec;10(4):423-37.
PMID: 22262534

In earlier models, synaptic plasticity forms the basis for cellular signaling underlying learning and memory. However, synaptic computation of learning and memory in the brain remains controversial. In this paper, we discuss ways in which synaptic plasticity remodels subcellular networks by deflecting trajectories in neuronal state-space as regulating patterns for the synthesis of dynamic continuity that form cognitive networks of associable representations through endogenous dendritic coding to consolidate memory.

Matched MeSH terms: Neuronal Plasticity/physiology*
Fulltext Mathematical modeling of subthreshold resonant properties in pyloric dilator neurons

Vazifehkhah Ghaffari B, Kouhnavard M, Aihara T, Kitajima T

Biomed Res Int, 2015;2015:135787.
PMID: 25960999 DOI: 10.1155/2015/135787

Various types of neurons exhibit subthreshold resonance oscillation (preferred frequency response) to fluctuating sinusoidal input currents. This phenomenon is well known to influence the synaptic plasticity and frequency of neural network oscillation. This study evaluates the resonant properties of pacemaker pyloric dilator (PD) neurons in the central pattern generator network through mathematical modeling. From the pharmacological point of view, calcium currents cannot be blocked in PD neurons without removing the calcium-dependent potassium current. Thus, the effects of calcium (I(Ca)) and calcium-dependent potassium (I(KCa)) currents on resonant properties remain unclear. By taking advantage of Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine the effects of changing resting membrane potential and those ionic currents on the resonance. Results show that changing the resting membrane potential influences the amplitude and frequency of resonance so that the strength of resonance (Q-value) increases by both depolarization and hyperpolarization of the resting membrane potential. Moreover, hyperpolarization-activated inward current (I(h)) and I(Ca) (in association with I(KCa)) are dominant factors on resonant properties at hyperpolarized and depolarized potentials, respectively. Through mathematical analysis, results indicate that I h and I(KCa) affect the resonant properties of PD neurons. However, I(Ca) only has an amplifying effect on the resonance amplitude of these neurons.

Matched MeSH terms: Neuronal Plasticity/physiology
Fulltext Rajyoga meditation induces grey matter volume changes in regions that process reward and happiness

Babu MGR, Kadavigere R, Koteshwara P, Sathian B, Rai KS

Sci Rep, 2020 09 30;10(1):16177.
PMID: 32999361 DOI: 10.1038/s41598-020-73221-x

Studies provide evidence that practicing meditation enhances neural plasticity in reward processing areas of brain. No studies till date, provide evidence of such changes in Rajyoga meditation (RM) practitioners. The present study aimed to identify grey matter volume (GMV) changes in reward processing areas of brain and its association with happiness scores in RM practitioners compared to non-meditators. Structural MRI of selected participants matched for age, gender and handedness (n = 40/group) were analyzed using voxel-based morphometric method and Oxford Happiness Questionnaire (OHQ) scores were correlated. Significant increase in OHQ happiness scores were observed in RM practitioners compared to non-meditators. Whereas, a trend towards significance was observed in more experienced RM practitioners, on correlating OHQ scores with hours of meditation experience. Additionally, in RM practitioners, higher GMV were observed in reward processing centers-right superior frontal gyrus, left inferior orbitofrontal cortex (OFC) and bilateral precuneus. Multiple regression analysis showed significant association between OHQ scores of RM practitioners and reward processing regions right superior frontal gyrus, left middle OFC, right insula and left anterior cingulate cortex. Further, with increasing hours of RM practice, a significant positive association was observed in bilateral ventral pallidum. These findings indicate that RM practice enhances GMV in reward processing regions associated with happiness.

Matched MeSH terms: Neuronal Plasticity/physiology*
Fulltext Acupuncture Alleviates CUMS-Induced Depression-Like Behaviors by Restoring Prefrontal Cortex Neuroplasticity

Li P, Huang W, Chen Y, Aslam MS, Cheng W, Huang Y, et al.

Neural Plast, 2023;2023:1474841.
PMID: 37179843 DOI: 10.1155/2023/1474841

PURPOSE: To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression.
METHODS: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR.
RESULTS: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05).
CONCLUSION: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

Matched MeSH terms: Neuronal Plasticity/physiology
Harnessing neuroplasticity: modern approaches and clinical future

Sasmita AO, Kuruvilla J, Ling APK

Int J Neurosci, 2018 Nov;128(11):1061-1077.
PMID: 29667473 DOI: 10.1080/00207454.2018.1466781

Background and purpose: Neurological diseases and injuries to the nervous system may cause inadvertent damage to neuronal and synaptic structures. Such phenomenon would lead to the development of neurological and neurodegenerative disorders which might affect memory, cognition and motoric functions. The body has various negative feedback systems which can induce beneficial neuroplastic changes in mediating some neuronal damage; however, such efforts are often not enough to ameliorate the derogatory changes. Materials and methods: Articles discussing studies to induce beneficial neuroplastic changes were retrieved from the databases, National Center for Biotechnology Information (NCBI) and MEDLINE, and reviewed. Results: This review highlights the significance of neuroplasticity in restoring neuronal functions and current advances in research to employ this positive cellular event by inducing synaptogenesis, neurogenesis, clearance of toxic amyloid beta (Aβ) and tau protein aggregates, or by providing neuroprotection. Compounds ranging from natural products (e.g. bilobalides, curcumin) to novel vaccines (e.g. AADvac1, RG7345) have been reported to induce long-lasting neuroplasticity in vitro and in vitro. Activity-dependent neuroplasticity is also inducible by regimens of exercises and therapies with instances in human studies proving major successes. Lastly, mechanical stimulation of brain regions through therapeutic hypothermia or deep brain stimulation has given insight on the larger scale of neuroplasticity within the nervous system. Conclusion: Harnessing neuroplasticity may not only offer an arm in the vast arsenal of approaches being taken to tackle neurological disorders, such as neurodegenerative diseases, but from ample evidence, it also has major implications in neuropsychological disorders.

Matched MeSH terms: Neuronal Plasticity/physiology*
Effectiveness of physiotherapy interventions in brain plasticity, balance and functional ability in stroke survivors: A randomized controlled trial

Rahayu UB, Wibowo S, Setyopranoto I, Hibatullah Romli M

NeuroRehabilitation, 2020;47(4):463-470.
PMID: 33164953 DOI: 10.3233/NRE-203210

BACKGROUND: Brain injuries such as strokes cause damage and death of the neuron cells. Physiotherapy interventions help to improve patient's performance and ability. However, this is only theorized but the impact of the physiotherapy intervention on brain plasticity is not known.
OBJECTIVE: The present study aimed to investigate the effect of physiotherapy interventions on brain neuroplasticity by evaluating the brain plasticity regeneration, balance and functional ability.
METHODS: A randomized controlled trial was conducted with 64 stroke patients from three hospitals in the Surakarta region, Indonesia. Control groups (n = 32) received conventional physiotherapy and intervention groups (n = 32) received neurorestoration protocol, which both lasted for seven days. Efficacy of the interventions were measured on brain-derived neurotropic factor serum analysis, Berg Balance Scale and Barthel Index, respectively.
RESULTS: Both groups showed improvements in all parameters but only balance and functional performance had a statistically significant outcome.
CONCLUSION: Neurorestoration protocol that combined several established physiotherapy interventions was effective in improving balance and functional ability of stroke patients in only a seven days period.

Matched MeSH terms: Neuronal Plasticity/physiology*