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Rehabilitation approaches for individuals with neurologic conditions have increasingly shifted toward promoting neuroplasticity for enhanced recovery and restoration of function. This review focuses on exercise strategies and non-invasive neuromodulation techniques that target neuroplasticity, including transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and peripheral nerve stimulation (PNS). We have chosen to focus on non-invasive neuromodulation techniques due to their greater potential for integration into routine clinical practice. We explore and discuss the application of these interventional strategies in four neurological conditions that are frequently encountered in rehabilitation settings: Parkinson's Disease (PD), Traumatic Brain Injury (TBI), stroke, and Spinal Cord Injury (SCI). Additionally, we discuss the potential benefits of combining non-invasive neuromodulation with rehabilitation, which has shown promise in accelerating recovery. Our review identifies studies that demonstrate enhanced recovery through combined exercise and non-invasive neuromodulation in the selected patient populations. We primarily focus on the motor aspects of rehabilitation, but also briefly address non-motor impacts of these conditions. Additionally, we identify the gaps in current literature and barriers to implementation of combined approaches into clinical practice. We highlight areas needing further research and suggest avenues for future investigation, aiming to enhance the personalization of the unique neuroplastic responses associated with each condition. This review serves as a resource for rehabilitation professionals and researchers seeking a comprehensive understanding of neuroplastic exercise interventions and noninvasive neuromodulation techniques tailored for specific diseases and diagnoses. [ABSTRACT FROM AUTHOR]

Inhibition of sucrose intake by cholecystokinin octapeptide (CCK-8) when infused directly into the celiac, superior mesenteric, and intravenous in rats was investigated. CCK-8 was infused in varying doses. Intraceliac infusions caused a significant reduction in sucrose intake, but this reduction did not depend on dose. Infusions to the superior mesenteric reduced intake only at the highest dose, 312 ng, while jugular infusions had no effect on intake. These results indicate that CCK receptors are located in various areas within the gastrointestinal tract.

A study of sucrose intake suppression by intravenous and continuous aortal or near celiac infusions of cholecystokinin octapeptide (CCK-8) in adult male Spargue-Dawley rats reveals that near-celiac administration of CCK-8 is more potent in the inhibition of sucrose intake. Near celiac infusion of CCK inhibits sucrose intake at all doses while only the highest doses of intravenous infusion exert the inhibitory effect. Behavioral observations reveal that continuous infusions of CCK-8 lead to increased satiety.

Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex. [ABSTRACT FROM AUTHOR]

Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards. • Modern tES suffers from a diversity of ill-defined nomenclature. • A consistent and clear taxonomy for tES will support clear and reproducible research. • This review presents the first comprehensive nomenclature scheme for tES. [ABSTRACT FROM AUTHOR]

Cox, James E., William J. Tyler, Alan Randich, Gary R. Kelm, Satinder S. Bharaj, Ronald J. Jandacek, and Stephen T. Meller. Suppression of food intake, body weight, and body fat by jejunal fatty acid infusions. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278: R604-R610, 2000.--Three experiments investigated effects of jejunal lipid infusions given on 4 or 21 consecutive days in adult, male Sprague-Dawley rats. In experiment 1, 7-h infusions of linoleic or oleic acid (0.2 ml/h for 7 h; total load = 11.5 kcal) on 4 consecutive days reduced total intake (ad libitum consumption of the liquid diet Boost, Mead Johnson, plus load) by ~15% and decreased weight gain compared with 4-day tests with saline administration. In experiment 2, linoleic acid at 0.1 ml/h for 7 h (5.7 kcal) was ineffective, whereas the same load delivered in 3.5 h produced effects similar in magnitude to those in the first experiment. In experiment 3, jejunal infusions of linoleic acid (0.2 ml/h for 7 h) on 21 consecutive days reduced mean total intake by 16%, body weight by 10%, and carcass fat by 48% compared with controls receiving saline. The net decrease in caloric intake may reflect the combined activation of pre- and postabsorptive mechanisms, and it suggests a possible treatment for obesity. linoleic acid; oleic acid; satiety; small intestine

Randich, Alan, William J. Tyler, James E. Cox, Stephen T. Meller, Gary R. Kelm, and Satinder S. Bharaj. Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278: R34-R43, 2000.--Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in ~50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain. fatty acids; triglycerides; satiety

Ultrasound (US) is recognized for its use in medical imaging as a diagnostic tool. As an acoustic energy source, US has become increasingly appreciated over the past decade for its ability to non-invasively modulate cellular activity including neuronal activity. Data obtained from a host of experimental models has shown that low-intensity US can reversibly modulate the physiological activity of neurons in peripheral nerves, spinal cord, and intact brain circuits. Experimental evidence indicates that acoustic pressures exerted by US act, in part, on mechanosensitive ion channels to modulate activity. While the precise mechanisms of action enabling US to both stimulate and suppress neuronal activity remain to be clarified, there are several advantages conferred by the physics of US that make it an appealing option for neuromodulation. For example, it can be focused with millimeter spatial resolutions through skull bone to deep-brain regions. By increasing our engineering capability to leverage such physical advantages while growing our understanding of how US affects neuronal function, the development of a new generation of non-invasive neurotechnology can be developed using ultrasonic methods. [ABSTRACT FROM AUTHOR]

Ultrasound (US) is widely known for its utility as a biomedical imaging modality. An abundance of evidence has recently accumulated showing that US is also useful for non-invasively modulating brain circuit activity. Through a series of studies discussed in this short review, it has recently become recognized that transcranial focused ultrasound can exert mechanical (non-thermal) bioeffects on neurons and cells to produce focal changes in the activity of brain circuits. In addition to highlighting scientific breakthroughs and observations that have driven the development of the field of ultrasonic neuromodulation, this study also provides a discussion of mechanisms of action underlying the ability of ultrasound to physically stimulate and modulate brain circuit activity. Exemplifying some forward-looking tools that can be developed by integrating ultrasonic neuromodulation with other advanced acoustic technologies, some innovative acoustic imaging, beam forming, and focusing techniques are briefly reviewed. Finally, the future outlook for ultrasonic neuromodulation is discussed, specifically in the context of applications employing transcranial focused ultrasound for the investigation, diagnosis, and treatment of neuropsychiatric disorders. [ABSTRACT FROM PUBLISHER]

A number of high-profile public figures hire ghost-tweeters to post to their social media accounts on their behalf, but no research has examined how this social media practice can affect followers' feelings of connection to the public figures. College students ( n = 132) participated in an online experiment to examine the effect of ghost-tweeting practices on parasocial interaction (PSI) with social media figures. Tweet authorship (use of a ghost-tweeter or not) was manipulated. Ghost-tweeting resulted in reduced PSI. Perceptions of distance, but not personal authenticity mediated this effect. However, authenticity and distance did serially mediate the relationship between ghost-tweeting and PSI. These findings shed light on the process of PSI with celebrities and other media figures on social network sites. [ABSTRACT FROM AUTHOR]

Increasing sensitivity of modern evaluation tools allows for the study of weaker electric stimulation effects on neural populations. In the current study we examined the effects of sham continuous theta burst (cTBS) transcranial magnetic stimulation to the left dorsolateral prefrontal cortex (DLPFC) upon somatosensory evoked potentials (SEP) and frontal-parietal phase coupling of alpha and beta bands. Sham TMS results in an induced electric field amplitude roughly 5% that of real TMS with a similar spatial extent in cortex. Both real and sham cTBS reduced the amplitude of the frontal P14-N30 SEP and increased local phase coupling in the alpha-beta frequency bands of left frontal cortex. In addition, both sham and real cTBS increased frontal-parietal phase coupling in the alpha-beta bands concomitant with an increase in amplitude of parietal P50-N70 complex. These data suggest that weak electric fields from sham cTBS can affect both local and downstream neuronal circuits, though in a different manner than high strength TMS. [ABSTRACT FROM AUTHOR]

All cells are influenced by mechanical forces. In the brain, force-generating and load-bearing proteins twist, turn, ratchet, flex, compress, expand and bend to mediate neuronal signalling and plasticity. Although the functions of mechanosensitive proteins have been thoroughly described in classical sensory systems, the effects of endogenous mechanical energy on cellular function in the brain have received less attention, and many working models in neuroscience do not currently integrate principles of cellular mechanics. An understanding of cellular-mechanical concepts is essential to allow the integration of mechanobiology into ongoing studies of brain structure and function. [ABSTRACT FROM AUTHOR]

Peripheral somatosensory circuits are known to respond to diverse stimulus modalities. The energy modalities capable of eliciting somatosensory responses traditionally belong to mechanical, thermal, electromagnetic, and photonic domains. Ultrasound (US) applied to the periphery has also been reported to evoke diverse somatosensations. These observations however have been based primarily on subjective reports and lack neurophysiological descriptions. To investigate the effects of peripherally applied US on human somatosensory brain circuit activity we recorded evoked potentials using electroencephalography and conducted functional magnetic resonance imaging of blood oxygen level-dependent (BOLD) responses to fingertip stimulation with pulsed US. We found a pulsed US waveform designed to elicit a mild vibration sensation reliably triggered evoked potentials having distinct waveform morphologies including a large double-peaked vertex potential. Fingertip stimulation with this pulsed US waveform also led to the appearance of BOLD signals in brain regions responsible for somatosensory discrimination including the primary somatosensory cortex and parietal operculum, as well as brain regions involved in hierarchical somatosensory processing, such as the insula, anterior middle cingulate cortex, and supramarginal gyrus. By changing the energy profile of the pulsed US stimulus waveform we observed pulsed US can differentially activate somatosensory circuits and alter subjective reports that are concomitant with changes in evoked potential morphology and BOLD response patterns. Based on these observations we conclude pulsed US can functionally stimulate different somatosensory fibers and receptors, which may permit new approaches to the study and diagnosis of peripheral nerve injury, dysfunction, and disease. [ABSTRACT FROM AUTHOR]

Deep brain stimulation and vagal nerve stimulation are therapeutically effective in treating some neurological diseases and psychiatric disorders. Optogenetic-based neurostimulation approaches are capable of activating individual synapses and yield the highest spatial control over brain circuit activity. Both electrical and light-based neurostimulation methods require intrusive procedures such as surgical implantation of electrodes or photon-emitting devices. Transcranial magnetic stimulation has also shown therapeutic effectiveness and represents a recent paradigm shift towards implementing less invasive brain stimulation methods. Magnetic-based stimulation, however, has a limited focusing capacity and lacks brain penetration power. Because ultrasound can be noninvasively transmitted through the skull to targeted deep brain circuits, it may offer alternative approaches to currently employed neuromodulation techniques. Encouraging this idea, literature spanning more than half a century indicates that ultrasound can modulate neuronal activity. In order to provide a comprehensive overview of potential mechanisms underlying the actions of ultrasound on neuronal excitability, here, I propose the continuum mechanics hypothesis of ultrasonic neuromodulation in which ultrasound produces effects on viscoelastic neurons and their surrounding fluid environments to alter membrane conductance. While further studies are required to test this hypothesis, experimental data indicate ultrasound represents a promising platform for developing future therapeutic neuromodulation approaches. [ABSTRACT FROM PUBLISHER]

Possessing the ability to noninvasively elicit brain circuit activity yields immense experimental and therapeutic power. Most currently employed neurostimulation methods rely on the somewhat invasive use of stimulating electrodes or photon-emitting devices. Due to its ability to noninvasively propagate through bone and other tissues in a focused manner, the implementation of ultrasound (US) represents a compelling alternative approach to current neuromodulation strategies. Here, we investigated the influence of low-intensity, low-frequency ultrasound (LILFU) on neuronal activity. By transmitting US waveforms through hippocampal slice cultures and ex vivo mouse brains, we determined LILFU is capable of remotely and noninvasively exciting neurons and network activity. Our results illustrate that LILFU can stimulate electrical activity in neurons by activating voltage-gated sodium channels, as well as voltage-gated calcium channels. The LILFU-induced changes in neuronal activity were sufficient to trigger SNARE-mediated exocytosis and synaptic transmission in hippocampal circuits. Because LILFU can stimulate electrical activity and calcium signaling in neurons as well as central synaptic transmission we conclude US provides a powerful tool for remotely modulating brain circuit activity. [ABSTRACT FROM AUTHOR]

Experience-dependent changes in neural circuits have traditionally been investigated several synapses downstream of sensory input. Whether experience can alter the strength of primary sensory synapses remains mostly unknown. To address this issue, we investigated the consequences of odor deprivation on synapses made by olfactory sensory axons in the olfactory bulb of rats. Odor deprivation triggered an increase in the probability of glutamate release from olfactory sensory neuron synapses. Deprivation also increased the amplitude of quantal synaptic currents mediated by AMPA- and NMDA-type glutamate receptors, as well as the abundance of these receptors in the glomerular region. Our results demonstrate that sensory experience is capable of modulating synaptic strength at the earliest stages of information transfer between the environment and an organism. Such compensatory experience-dependent changes may represent a mechanism of sensory gain control. [ABSTRACT FROM AUTHOR]

The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood. We show here that brain-derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in organotypic slice cultures prepared from postnatal rat hippocampal slices. This effect was observed also in the absence of action potentials, and even when miniature synaptic transmission was inhibited with botulinum neurotoxin C (BoNT/C). There were, however, marked differences in the morphology of individual spines induced by BDNF across these different levels of spontaneous ongoing synaptic activity. During both normal synaptic transmission, and when action potentials were blocked with TTX, BDNF increased the proportion of stubby, type-I spines. However, when SNARE-dependent vesicular release was inhibited with BoNT/C, BDNF increased the proportion of thin, type-III spines. Our results indicate that BDNF increases spine density irrespective of the levels of synaptic transmission. In addition, miniature synaptic transmission provides sufficient activity for the functional translation of BDNF-triggered spinogenesis into clearly defined morphological spine types, favouring those spines potentially responsible for coordinated Ca&sup2+; transients thought to mediate synaptic plasticity. We propose that BDNF/TrkB signalling represents a mechanism of expression of both morphological and physiological homeostatic plasticity in the hippocampus, leading to a more efficient synaptic information transfer across widespread levels of synaptic activity. [ABSTRACT FROM AUTHOR]

Focuses on a study which provided an update on evidence demonstrating that neurotrophins (NT) enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. Modes of synaptic vesicle retrieval that synapses may use during high-frequency synaptic transmission; Misconception on experience-dependent changes in the efficacy of fast synaptic transmission; Features of neurotrophins.

Using targeted mouse mutants and pharmacologic inhibition of αCaMKII, we demonstrate that the αCaMKII protein, but not its activation, autophosphorylation or its ability to phosphorylate synapsin I, is required for normal short-term presynaptic plasticity. Furthermore, αCaMKII regulates the number of docked vesicles independent of its ability to be activated. These results indicate that αCaMKII has a nonenzymatic role in short-term presynaptic plasticity at hippocampal CA3-CA1 synapses. [ABSTRACT FROM AUTHOR]

The article discusses research on the use of ultrasound to conduct nonivasive functional neurosurgery. It references the study "High Intensity Focused Ultrasound for Non-Invasive Functional Neurosurgery," by Ernst Martin and colleagues, published in "Annals of Neurology." The authors argue that the study findings showed the possibilities offered by magnetic resonance imaging-guided focused ultrasound (MRgFUS) for the treatment of neurological disorders.

We engineered a transdermal neuromodulation approach that targets peripheral (cranial and spinal) nerves and utilizes their afferent pathways as signaling conduits to influence brain function. We investigated the effects of this transdermal electrical neurosignaling (TEN) method on sympathetic physiology under different experimental conditions. The TEN method involved delivering high-frequency pulsed electrical currents to ophthalmic and maxillary divisions of the right trigeminal nerve and cervical spinal nerve afferents. Under resting conditions, TEN significantly suppressed basal sympathetic tone compared to sham as indicated by functional infrared thermography of facial temperatures. In a different experiment, subjects treated with TEN reported significantly lower levels of tension and anxiety on the Profile of Mood States scale compared to sham. In a third experiment when subjects were experimentally stressed TEN produced a significant suppression of heart rate variability, galvanic skin conductance, and salivary α-amylase levels compared to sham. Collectively these observations demonstrate TEN can dampen basal sympathetic tone and attenuate sympathetic activity in response to acute stress induction. Our physiological and biochemical observations are consistent with the hypothesis that TEN modulates noradrenergic signaling to suppress sympathetic activity. We conclude that dampening sympathetic activity in such a manner represents a promising approach to managing daily stress. [ABSTRACT FROM AUTHOR]

Using the theory of motivated information management (TMIM), this study explored how individuals manage information about romantic partners’ past relationships, a typically taboo topic (Baxter & Wilmot, 1985). A sample (N= 146) of undergraduate students currently involved in romantic relationships was used to test TMIM’s predictions regarding cognitive, emotional, and communicative processes involved in information-management decisions regarding a partner’s previous relationships. The hypothesized models were supported for negative emotions (i.e., anger and fear) but not for happiness as a representative positive emotion. Further, efficacy emerged as a significant mediator of the relationships between the negative emotions and information-management strategies and of the associations between outcome assessments and information-management strategies. Implications and future research directions are discussed. [ABSTRACT FROM PUBLISHER]

Summary: Electromagnetic-based methods of stimulating brain activity require invasive procedures or have other limitations. Deep-brain stimulation requires surgically implanted electrodes. Transcranial magnetic stimulation does not require surgery, but suffers from low spatial resolution. Optogenetic-based approaches have unrivaled spatial precision, but require genetic manipulation. In search of a potential solution to these limitations, we began investigating the influence of transcranial pulsed ultrasound on neuronal activity in the intact mouse brain. In motor cortex, ultrasound-stimulated neuronal activity was sufficient to evoke motor behaviors. Deeper in subcortical circuits, we used targeted transcranial ultrasound to stimulate neuronal activity and synchronous oscillations in the intact hippocampus. We found that ultrasound triggers TTX-sensitive neuronal activity in the absence of a rise in brain temperature (<0.01°C). Here, we also report that transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately 2 mm and does not require exogenous factors or surgical invasion. [Copyright &y& Elsevier]