Neuromodulation

This paper introduces a new model of artificial cognitive architecture for intelligent systems, the Neuromodulating Cognitive Architecture (NEUCOGAR). It is biomimetically inspired and adapts the neuromodulators role of human brains into computational environments. This way we aim at achieving more efficient Artificial Intelligence solutions based on the biological inspiration of the deep functioning of human brain, which is highly emotional. The analysis of new data obtained from neurology, psychology and even philosophical or anthropological contributions of the study of the emotion role into cognitive processes allow us to generate a mapping of monoamine neuromodulators and to apply it to computational system parameters. Thus we can make artificial cognitive systems that better perform more complex tasks (regarding information selection and discrimination, attention, innovation, creativity,) as well as able to show affordable emotional relationships with human users.

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medi...

Background: Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events.

Besides neuroanatomical changes, neuromodulatory mechanisms are also compromised during aging. Neural network models are suitable tools for exploring the relatively broad and homogenous neuromodulatory influences on cortical function. Computational approaches for understanding neuromodulation of the dynamic properties of cortical function and recent neurocomputational theories relating different aspects of cognitive aging with declines in neuromodulation are reviewed. Considered within an integrative cross-level neurocomputational framework, aging-related decline in dopaminergic neuromodulation reduces the fidelity of neural information and gives rise to less distinctive neural pattern representations that may underlie various facets of aging cognitive and, possibly also, sensorimotor phenomena. q : S 0 1 4 9 -7 6 3 4 ( 0 2 ) 0 0 0 6 6 -0 Neuroscience and Biobehavioral Reviews 26 www.elsevier.com/locate/neubiorev

Background and purpose:Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.Experimental approach:Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections.Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections.Key resultsOur results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT.Our results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT.Conclusions and implications:These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.British Journal of Pharmacology (2007) 151, 1109–1116; doi:10.1038/sj.bjp.0707313These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.British Journal of Pharmacology (2007) 151, 1109–1116; doi:10.1038/sj.bjp.0707313

An intrathecal opioid infusion using an implanted programmable pump i s frequently used for controlling refractory pain. Morphine, which is the only opioid presently approved by the FDA for use in such pumps, occasionally fails to work or i s not tolerated by the patient; therefore other opioids are considered for infusions. When switching from one drug to another, it is important to consider not only equianalgesic dose conversions, but also lipophilicity. We report on three cases that demonstrate the need to use only a fraction of the equianalgesic dose when shifting from lipophilic to nonlipophilic opioids in such infusions. H KEY WORDS: lntrasplnal-neuromodulation-opiatespain-pumps.

A prospective, open label, multicenter clinical trial confirmed the functionality of a new spinal cord stimulation (SCS) system for the treatment of chronic, intractable pain of the trunk and/or limbs. Materials and Methods. Sixty-five subjects tested a rechargeable 16-channel SCS system with individual current control of each contact on one or two percutaneous eight-contact epidural leads. After baseline measurements, subjects were tracked on pain ratings and complication rates for up to 18 months. Results. After a trial period, 75% of subjects underwent permanent implantation of the entire SCS system. More than one-half the implanted subjects experienced 50% or greater relief of pain after permanent implantation; some subjects reported relief of 90% or more of their pain. The most common complications after permanent implantation were lead migration, uncomfortable stimulation, and component failure; most resolved after reprogramming or device replacement. Conclusions. The new SCS system provided good pain relief to a majority of subjects, and the results confirm a favorable safety and efficacy profile for the SCS system.

PURPOSE. to investigate the acceptability, efficacy, and effect duration of translingual neurostimulation (TLNS) plus standard therapeutic exercise program (TEP) to improve motor skills in children with cerebral palsy (CP). Methods: Participants aged 2-17 years (n = 134) diagnosed with spastic diplegia CP with coordination and mobility symptoms were enrolled at Sestroretsk City hospital № 40. Participants were offered one of two treatment regimens: either TEP plus TLNS with the Portable Neuromodulation Stimulator (PoNS™) - experimental arm or TEP alone (control). the treatment course continued for ten days (2 weeks, excluding two weekend days). In the experimental group and TEP, TLNS was applied twice a day, 20 minutes each during exercises, morning, and afternoon, at least 3 hours between sessions. Assessments before and after therapy courses measured spasticity, balance, and motor skills. Either treatment could be repeated several times (6-12 months between courses). All children were assessed before and after a course round of therapy using standard scales for spasticity, balance, and motor skills (Ashworth scale, berg scale, Gross motor function Classification System, functional movement Screen). Results: Both groups of patients showed improvement; however, the improvement was significantly more significant in the experimental group across all scales, observed in all ages, and largely sustained for 6-12 months. CONCLUSIONS. TLNS plus TEP can be considered as a novel and promising strategy to improve neurorehabilitation outcomes in children with CP, offering broad implications for the development and use of TLNS in CP.

Plasticity is an intrinsic property of the human brain and represents evolution's invention to enable the nervous system to escape the restrictions of its own genome and thus adapt to environmental pressures, physiologic changes, and experiences. Dynamic shifts in the strength of preexisting connections across distributed neural networks, changes in task-related cortico-cortical and corticosubcortical coherence and modifications of the mapping between behavior and neural activity take place in response to changes in afferent input or efferent demand. Such rapid, ongoing changes may be followed by the establishment of new connections through dendritic growth and arborization. However, they harbor the danger that the evolving pattern of neural activation may in itself lead to abnormal behavior. Plasticity is the mechanism for development and learning, as much as a cause of pathology. The challenge we face is to learn enough about the mechanisms of plasticity to modulate them to achieve the best behavioral outcome for a given subject. 377 Annu. Rev. Neurosci. 2005.28:377-401. Downloaded from arjournals.annualreviews.org by HARVARD COLLEGE on 07/17/05. For personal use only. Pascual-Leone et al. Annu. Rev. Neurosci. 2005.28:377-401. Downloaded from arjournals.annualreviews.org by HARVARD COLLEGE on 07/17/05. For personal use only. www.annualreviews.org • The Plastic Human Brain Cortex 389 Annu. Rev. Neurosci. 2005.28:377-401. Downloaded from arjournals.annualreviews.org by HARVARD COLLEGE on 07/17/05. For personal use only.

Epilepsy surgery is an effective treatment for properly selected patients with intractable seizures. However, many patients with medically intractable epilepsy are not excellent candidates for surgical resection of the epileptogenic zone. Due to recent advances in computer technology and bioengineering, several novel techniques are receiving increasing interest for their role in the care of people with epilepsy. Neuromodulation is an emerging surgical option to be used when conventional resective surgery is not indicated. We review the indications and expected outcomes of neuromodulatory treatments currently available for the treatment of refractory epilepsy, i.e., vagus nerve stimulation, deep brain stimulation, stereotactic radiosurgery, and multiple subpial transections.

The phenomenon of anhedonia, the inability to experience pleasure, is one of the essential elements for the diagnosis of depressive disorders. According to the criteria of both the ICD-10 and the DSM-IV, the presence of this symptom is crucial for the diagnosis of depressive disorders. In recent years scientific approaches using animal studies and projects of functional imaging have allowed the development of a new concept of the pathophysiology of anhedonia. The hypothesis that functional changes within the mesolimbic reward system could represent the neural correlate of anhedonia has contributed to a new concept of depressive disorders and allows testing of new therapeutic options for patients suffering from very resistant forms of depression. By using the method of deep brain stimulation present clinical studies try to ascertain whether the symptom of anhedonia can be alleviated by influencing the neural activity of the reward system. This article will give a critical overview about the background for new therapeutic approaches and illuminates the results of these studies.

Cyprus (UCY) invite expressions of interest for applications for the ONISILOS Marie Skłodowska-Curie Actions (MSCA) COFUND project. CeMAR, CAN, and DISCONSO will jointly mentor and support selected eligible candidates with a background in medieval studies and/or cognitive neuroscience in preparing an application for an Individual Fellowship. All supported applications will have to be on topics that fall within the theme of medieval emotions and cognitive neuroscience.

People with anxiety disorders show an attentional bias for threat (AB), and Attention Bias Modification (ABM) procedures have been found to reduce this bias. However, the underlying processes accounting for this effect remain poorly understood. One explanation suggests that ABM requires the modification of attention control, driven by the recruitment of the dorsolateral prefrontal cortex (DLPFC). In the present double-blind study, we examined whether modifying left DLPFC activation influences the effect of ABM on AB. We used transcranial direct current stimulation (tDCS) to directly modulate cortical excitability of the left DLPFC during an ABM procedure designed to reduce AB to threat. Anodal tDCS increases excitability, whereas cathodal tDCS decreases it. We randomly assigned highly trait-anxious individuals to one of three conditions: 1) ABM combined with cathodal tDCS, 2) ABM combined with anodal tDCS, or 3) ABM combined with sham tDCS. We assessed the effects of these manipulat...

Objective: Nonpulsatile tinnitus is an auditory phantom percept characterized as a tone, or a noise-like sound such as a hissing or buzzing sound or polyphonic, in the absence of any objective physical sound source. Although advances have been made in symptomatic pharmacologic and nonpharmacologic treatments, these treatments are unable to eliminate the tinnitus sensation in most patients. A novel approach using noninvasive and invasive neuromodulation has emerged as an interesting and promising modality for tinnitus relief.

It is important to find new treatments for addiction due to high relapse rates despite current interventions and due to expansion of the field with non-substance related addictive behaviors. Neuromodulation may provide a new type of treatment for addiction since it can directly target abnormalities in neurocircuits. We review literature on five neuromodulation techniques investigated for efficacy in substance related and behavioral addictions: transcranial direct current stimulation (tDCS), (repetitive) transcranial magnetic stimulation (rTMS), EEG, fMRI neurofeedback and deep brain stimulation (DBS) and additionally report on effects of these interventions on addiction-related cognitive processes. While rTMS and tDCS, mostly applied at the dorsolateral prefrontal cortex, show reductions in immediate craving for various addictive substances, placebo-responses are high and long-term outcomes are understudied. The lack in well-designed EEG-neurofeedback studies despite decades of investigation impedes conclusions about its efficacy. Studies investigating fMRI neurofeedback are new and show initial promising effects on craving, but future trials are needed to investigate long-term and behavioral effects. Case studies report prolonged abstinence of opioids or alcohol with ventral striatal DBS but difficulties with patient inclusion may hinder larger, controlled trials. DBS in neuropsychiatric patients modulates brain circuits involved in reward processing, extinction and negative-reinforcement that are also relevant for addiction. To establish the potential of neuromodulation for addiction, more randomized controlled trials are needed that also investigate treatment duration required for long-term abstinence and potential synergy with other addiction interventions. Finally, future advancement may be expected from tailoring neuromodulation techniques to specific patient (neurocognitive) profiles.

We proposed a novel method of chronic electroacupuncture (EA) using implanted electrodes for the treatment of chronic chemotherapy-induced nausea and vomiting (CINV). We aimed to establish a rodent model of delayed emesis and explore EA effects on kaolin intake. Saline-treated and cisplatin-treated rats underwent chronic placement of electrodes at bilateral PC6 and ST36 acupoints. Tested EA parameters included sham EA; EA at frequency of 10, 20, or 40 Hz; duration of one, three, or six hours; pulse width of 0.3, 0.6, or 1.2 msec; and amplitude of 0.4-2.0 mA. Kaolin intake was measured following each treatment. 1) Cisplatin increased kaolin intake (p ≤ 0.01 vs. saline). 2) In terms of reduction of kaolin intake vs. sham EA: a) EA at a frequency of 10 Hz was effective only when given for three hours (p = 0.0004). b) EA at a frequency of 20 Hz was effective when given for either one or three hours, with three hours being most effective (p = 0.007 and 0.005, respectively). c) EA at a fr...

Sleep researchers in different disciplines disagree about how fully dreaming can be explained in terms of brain physiology. Debate has focused on whether REM sleep dreaming is qualitatively different from nonREM (NREM) sleep and waking. A review of psychophysiological studies shows clear quantitative differences between REM and NREM mentation and between REM and waking mentation. Recent neuroimaging and neurophysiological studies also differentiate REM, NREM, and waking in features with phenomenological implications. Both evidence and theory suggest that there are isomorphisms between the phenomenology and the physiology of dreams. We present a three-dimensional model with specific examples from normally and abnormally changing conscious states.

Background/Objectives: Interhemispheric inhibition in the brain plays a dynamic role in the production of voluntary unimanual actions. In stroke, the interhemispheric imbalance model predicts the presence of asymmetry in interhemispheric inhibition, with excessive inhibition from the contralesional hemisphere limiting maximal recovery. Stimulation methods to reduce this asymmetry in the brain may be promising as a stroke therapy, however determining how to best measure and modulate interhemispheric inhibition and who is likely to benefit, remain important questions. Methods: This review addresses current understanding of interhemispheric inhibition in the healthy and stroke lesioned brain. We present a review of studies that have measured interhemispheric inhibition using different paradigms in the clinic, as well as results from recent animal studies investigating stimulation methods to target abnormal inhibition after stroke. Main findings/Discussion: The degree to which asymmetric interhemispheric inhibition impacts on stroke recovery is controversial, and we consider sources of variation between studies which may contribute to this debate. We suggest that interhemispheric inhibition is not static following stroke in terms of the movement phase in which it is aberrantly engaged. Instead it may be dynamically increased onto per-ilesional areas during early movement, thus impairing motor initiation. Hence, its effect on stroke recovery may differ between studies depending on the technique and movement phase of eliciting the measurement. Finally, we propose how modulating excitability in the brain through more specific targeting of neural elements underlying interhemispheric inhibition via stimulation type, location and intensity may raise the ceiling of recovery following stroke and enhance functional return.

Addiction is a chronic relapsing brain disease with significant economical and medical burden
on the societies but with limited effectiveness in the available treatment options. Better understanding
of the chemical, neuronal, regional, and network alterations of the brain due to drug
abuse can ultimately lead to tailoring individualized and more effective interventions. To this
end, employing new assessment and intervention procedures seems crucial. Noninvasive brain
stimulation (NIBS) techniques including transcranial electrical and magnetic stimulations
(tES and TMS) have provided promising opportunities for the addiction medicine in two main
domains: (1) providing new insights into neurochemical and neural circuit changes in the human
brain cortex and (2) understanding the role of different brain regions by using NIBS and
modulating cognitive functions, such as drug craving, risky decision making, inhibitory control
and executive functions to obtain specific treatment outcomes. In spite of preliminary positive
results, there are several open questions, which need to be addressed before routine
clinical utilization of NIBS techniques in addiction to medicine, such as how to account
for interindividual differences, define optimal cognitive and neural targets, optimize stimulation
protocols, and integrate NIBS with other therapeutic methods. Therefore, in this chapter
we revise the available literature on the use of NIBS (TMS and tES) in the diagnostic, prognostic,
and therapeutic aspects of the addiction medicine.

Objective: The medial prefrontal cortex (mPFC) is a highly connected cortical region that acts as a hub in major large-scale brain networks. Its dysfunction is associated with a number of psychiatric disorders, such as schizophrenia, autism, depression, substance use disorder (SUD), obsessive-compulsive disorder (OCD), and anxiety disorders. Repetitive transcranial magnetic stimulation (rTMS) studies targeting the mPFC indicate that it may be a useful therapeutic resource in psychiatry due to its selective modulation of this area and connected regions. Methods: This review examines six mPFC rTMS trials selected from 697 initial search results. We discuss the main results, technical and methodological details, safety, tolerability, and localization strategies. Results: Six different protocols were identified, including inhibitory (1 Hz) and excitatory (5, 10, and 20 Hz) frequencies applied therapeutically to patient populations diagnosed with major depressive disorder, OCD, autistic spectrum disorder, SUD, specific phobia, and post-traumatic stress disorder (PTSD). In the OCD and acrophobia trials, rTMS significantly reduced symptoms compared to placebo. Conclusion: These protocols were considered safe and add interesting new evidence to the growing body of mPFC rTMS literature. However, the small number and low methodological quality of the studies indicate the need for further research.

The possibility to use non-invasive brain stimulation to modulate reading performance in individuals with developmental dyslexia (DD) has been recently explored by few empirical investigations. The present systematic review includes nine studies which have employed transcranial direct current stimulation (tDCS) aiming at improving reading abilities in both typical readers and individuals with DD. Anodal tDCS over the left temporo-parietal cortex—a region which is typically involved in phonological and orthographic processing during reading tasks and underactive in individuals with DD—was the most frequently used montage. The majority of studies employing such stimulation protocol showed significant improvement in differential reading subprocesses. More precisely, word decoding was improved in adult readers, whereas non-word and low-frequency word reading in younger individuals. Furthermore, tDCS was found to be specifically effective in poor readers and individuals with DD rather than typical readers, in spite of the specific brain region targeted by the stimulation; Left frontal, left temporo-parietal, and right cerebellar tDCS failed to modulate reading in already proficient readers. Overall, tDCS appears to be a promising remedial tool for reading difficulties, even when applied to younger populations with reading problems. Further empirical evidence is needed to confirm the potential of neuromodulation as a successful intervention method for DD.

Migraine is a chronic brain disorder that is believed to be due to dysfunction of the brain and brainstem that result in dysmodulation of sensory processing of the head and vascular tone. The exact pathomechanism of migraine is not known but some genes including mutations in the sodium and calcium channels and Na + /K + pump have been implicated in migraine with aura. 1-8 Several drugs are currently used in the acute and preventive treatment of migraine. These include the non-steroidal anti-inflammatory drugs, the triptan family, anti-epileptic drugs, beta-blockers, calcium channel blockers, steroids, and recently antibodies against calci-tonin gene-related peptide (CGRP) or its receptor among other drugs. 5,9 Some other drugs are under investigation and the CGRP receptor antagonists (the gepant family drugs), were discontinued although other drugs in this category are still under investigation. 10-16 However, there are some medically intractable headaches or unsatisfactory patient management or medications are poorly tolerated, therefore, additional treatment options might be helpful. A number of nonpharmacological methods such as education, reassurance, avoiding the triggers of migraine, and physical and/or complementary medicine when appropriate, have also been recommended in the treatment of migraine and other headaches. 17,18 Dietary modifications and lifestyle changes have also been suggested. 19 Other methods such as physical therapy with relaxation and thermal biofeedback have also been used in the treatment of migraine. 20,21 A recent meta-analysis of biofeedback in treatment of pediatric migraine shows some effectiveness but more research is needed. 22 A recent pilot randomized controlled trial shows that frontal electromyography bio-feedback added to traditional pharmacological therapy is promising in the prophylactic treatment of medication overuse headache by reducing the frequency of headache and analgesic intake. 23 Other nonpharmacological approaches such as behavioral, and body/mind treatment of headache were reported to be effective 24 and an 8-week mindfulness-based stress reduction method by meditation in adult migraine patients shows some beneficial effects 25 although more studies are needed. Other methods such as massage therapy of the neck and upper thoracic region 26-28 or acupuncture studies have shown some efficacy in the treatment of chronic headache 29-31 but more research is necessary. 32 The nonpharmacological treatment options of migraine warrants a review paper by itself to understand current opinion in this area. However, our focus in this issue will be on neuromodulation by electrical stimulation of peripheral and central nerves/neurons that are currently being used in clinical studies for the acute and preventive treatment of migraine. 33 Currently, electrical stimulation of various nerves is being used through a number of

Vagus nerve stimulation is an interesting new approach to treating neuropsychiatric diseases within the class of brain-stimulation devices sometimes labeled 'neuromodulators'. With vagus nerve stimulation, a battery-powered generator implanted in the chest wall connects to a wire wrapped around the vagus nerve in the neck, and sends intermittent pulses of electricity along the nerve directly into the brain. This mechanism takes advantage of the natural role of the vagus nerve in conveying information into the brain concerning homeostatic information (e.g., hunger, chest pain and respirations). Vagus nerve stimulation therapy is US FDA approved for the adjunctive treatment of epilepsy and has recently been FDA approved for the treatment of medication-resistant depression. Owing to its novel route into the brain, it has no drug-drug interactions or systemic side effects. This treatment also appears to have high long-term tolerability in patients, with low rates of patients relapsing on vagus nerve stimulation or becoming tolerant. However, alongside the excitement and enthusiasm for this new treatment, a lack of Class I evidence of efficacy in treating depression is currently slowing down adoption by psychiatrists. Much more research is needed regarding exactly how to refine and deliver the electrical pulses and how this differentially affects brain function in health and disease.

Background: Electrical and magnetic trans-spinal stimulation can be used to increase the motor output of multiple spinal segments and modulate cortico-spinal excitability. The application of direct current through the scalp as well as repetitive transcranial magnetic stimulation are known to influence brain excitability, and hence can also modulate other central nervous system structures, including spinal cord.

Developmental dyslexia (DD) is associated with deficiencies in temporal processing of auditory stimuli, depending on atypical oscillatory neural activity, that are considered to contribute to phonological and reading impairments. To induce a more accurate entrainment to the spectral properties of auditory stimuli in dyslexic readers, we explored the possibility to synchronize speech prosody during reading with an acoustic stimulus presented at a regular pace. Accordingly, an intervention program for DD, called Rhythmic Reading Training, was devised. Several test-training-retest studies supported the efficacy of this new methodology on reading skills of primary and high-school students with DD under different conditions. Finally, preliminary results of the application of RRT combined with neuromodulation (i.e., tDCS) in undergraduate students with DD are presented.

This paper introduces a new model of artificial cognitive architecture for intelligent systems, the Neuromodulating Cognitive Architecture (NEUCOGAR). It is biomimetically inspired and adapts the neuromodulators role of human brains into computational environments. This way we aim at achieving more efficient Artificial Intelligence solutions based on the biological inspiration of the deep functioning of human brain, which is highly emotional. The analysis of new data obtained from neurology, psychology and even philosophical or anthropological contributions of the study of the emotion role into cognitive processes allow us to generate a mapping of monoamine neuromodulators and to apply it to computational system parameters. Thus we can make artificial cognitive systems that better perform more complex tasks (regarding information selection and discrimination, attention, innovation, creativity,) as well as able to show affordable emotional relationships with human users.

This pooled individual data (PID)-based meta-analysis collectively assessed the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on various neuropathic pain states based on their neuroanatomical hierarchy. Available randomized controlled trials (RCTs) were screened. PID was coded for age, gender, pain neuroanatomical origins, pain duration, and treatment parameters analyses. Coded pain neuroanatomical origins consist of peripheral nerve (PN); nerve root (NR); spinal cord (SC); trigeminal nerve or ganglion (TGN); and post-stroke supraspinal related pain (PSP). Raw data of 149 patients were extracted from 5 (1 parallel, 4 cross-over) selected (from 235 articles) RCTs. A significant (P < .001) overall analgesic effect (mean percent difference in pain visual analog scale (VAS) score reduction with 95% confidence interval) was detected with greater reduction in VAS with rTMS in comparison to sham. Including the parallel study (Khedr et al), the TGN subgroup was found to have the greatest analgesic effect (28.8%), followed by PSP (16.7%), SC (14.7%), NR (10.0%), and PN (1.5%). The results were similar when we excluded the parallel study with the greatest analgesic effect observed in TGN (33.0%), followed by SC (14.7%), PSP (10.5%), NR (10.0%), and PN (1.5%). In addition, multiple (vs single, P = .003) sessions and lower (>1 and #10 Hz) treatment frequency range (vs >10 Hz) appears to generate better analgesic outcome. In short, rTMS appears to be more effective in suppressing centrally than peripherally originated neuropathic pain states.

Brain-gut axis represents a complex reflex circuit that integrates the communication between cortex and the digestive system. Disturbances of the neuromodulatory processes in the brain-gut axis generate functional digestive disorders mainly centered on the pain symptoms and motility disorders. This article reviews structural and patho-physiological aspects of the brain-gut axis and explains how the neuromodulatory interventions currently used in order to treat GI conditions related to the brain-gut axis disturbances. The neuromodulation can be realized by pharmacological targeting mainly receptors in the periphery or using electrical stimulation applied at different levels of the nervous system or directly in the muscular layers of the bowels resulting in modulation of the digestive system activity. The efficacy of the methods using electrostimulation is dependent on the parameters of the physical system used: amplitude, frequency, burst time of the electrical current and also the positioning of the electrodes. While pharmacological interventions are largely used at the moment, neuromodulatory interventions involving electrical stimulation showed clinical efficacy in research trials and have promise.

Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

Drug dependence is a disorder that affects the whole subject but specially its mental health. Several brain areas involved in drug addiction have been described and the prefrontal cortex is pointed as a key structure involved in the control over drug intake behaviour. Here, we summarize the involvement of some prefrontal sites in drug abuse and we present relevant findings that point the neuromodulation of the prefrontal cortex as a promising additional tool in the treatment of addiction.

BACKGROUND:

Spinal cord stimulation (SCS) is a standard treatment option for chronic neuropathic pain. However, some anatomical pain distributions are known to be difficult to cover with traditional SCS-induced paresthesias and/or may also induce additional, unwanted stimulation. We present the results from a retrospective review of data from patients with groin pain of various etiologies treated using neuromodulation of the dorsal root ganglion (DRG).
METHODS:

Data from 29 patients with neuropathic groin pain were reviewed. Patients underwent trial therapy where specifically designed leads were implanted at the target DRGs between T12 and L4. Patients who had a successful trial (> 50% improvement) received the fully implantable neuromodulation system. Pain scores were captured on a visual analog scale (VAS) at baseline and at regular follow-up visits.
RESULTS:

Twenty-five patients (86.2%) received fully implantable neurostimulators, and the average follow-up period was 27.8 ± 4.3 (standard error of the mean, SEM) weeks. The average pain reduction was 71.4 ± 5.6%, and 82.6% (19/23) of patients experienced a > 50% reduction in their pain at the latest follow-up. Individual cases showed improvement with a variety of etiologies and pain distributions; a subanalysis of postherniorrhaphy cohort also showed significant improvement.
CONCLUSIONS:

Early findings suggest that neuromodulation of the DRG may be an effective treatment for chronic neuropathic pain conditions in the groin region. This technique offers a useful alternative for pain conditions that do not always respond optimally to traditional SCS therapy. Neuromodulation of the DRG provided excellent cross-dermatomal paresthesia coverage, even in cases with patients with discrete pain areas. The therapy can be specific, sustained, and independent of body position.