Combined Brain Stimulation Research Articles

Modulating fluid intelligence performance through combined cognitive training and brain stimulation

It is debated whether cognitive training of specific executive functions leads to far transfer effects, such as improvements in fluid intelligence (Gf). Within this context, transcranial direct current stimulation and recently also novel protocols such as transcranial random noise and alternating current stimulation are being investigated with regards to their ability to enhance cognitive training outcomes.We compared the effects of four different transcranial electrical brain stimulation protocols in combination with nine daily computerized training sessions on Gf.82 participants were randomly assigned to receive transcranial direct current stimulation (tDCS), random noise stimulation (tRNS), multifocal alternating current stimulation at 40 Hz (mftACS), or multifocal tDCS (mftDCS) in combination with an adaptive and synergistic executive function (EF) training, or to a no-contact control group. EF training consisted of gamified tasks drawing on isolated as well as integrated executive functions (working memory, inhibition, cognitive flexibility). Transfer was assessed with a combined measure of Gf including three established tests (Bochumer Matrizentest - BOMAT, Raven's Advanced Progressive Matrices - RAPM, and Sandia Matrices). We found significant improvements in Gf for the tDCS, mftDCS, and tRNS groups when compared with the no-contact group. In contrast, the mftACS group did not improve significantly and showed a similar pattern as the no-contact group. Mediation analyses indicated that the improvement in Gf was mediated through game progression in the mftDCS and tRNS group. Electrical brain stimulation in combination with sustained EF training can lead to transfer effects in Gf, which are mediated by training progression.

Child and Caregiver Perspectives of a Combined Brain Stimulation and Constraint-Induced Movement Therapy Trial

Abstract Date Presented 3/31/2017 Novel interventions pairing noninvasive brain stimulation and rehabilitation are emerging for children with stroke. Feedback from pediatric clinical trial participants and caregivers is reviewed to guide future investigations and translation of novel interventions. Primary Author and Speaker: Tonya Rich Contributing Authors: Chao-Ying Chen, Timothy Feyma, Gregg Meekins, Marcie Ward, Linda E. Krach, Bernadette Gillick

Editorial: Non-invasive Brain Stimulation and Plasticity Changes in Aging.

Editorial: Non-invasive Brain Stimulation and Plasticity Changes in Aging.

Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects

BackgroundThere is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training.MethodsIn total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used.ResultsThe VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D).ConclusionsThe combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke.Electronic supplementary materialThe online version of this article (doi:10.1186/1743-0003-11-124) contains supplementary material, which is available to authorized users.

Best of both worlds: promise of combining brain stimulation and brain connectome.

Transcranial current brain stimulation (tCS) is becoming increasingly popular as a non-pharmacological non-invasive neuromodulatory method that alters cortical excitability by applying weak electrical currents to the scalp via a pair of electrodes. Most applications of this technique have focused on enhancing motor and learning skills, as well as a therapeutic agent in neurological and psychiatric disorders. In these applications, similarly to lesion studies, tCS was used to provide a causal link between a function or behavior and a specific brain region (e.g., primary motor cortex). Nonetheless, complex cognitive functions are known to rely on functionally connected multitude of brain regions with dynamically changing patterns of information flow rather than on isolated areas, which are most commonly targeted in typical tCS experiments. In this review article, we argue in favor of combining tCS method with other neuroimaging techniques (e.g., fMRI, EEG) and by employing state-of-the-art connectivity data analysis techniques (e.g., graph theory) to obtain a deeper understanding of the underlying spatiotemporal dynamics of functional connectivity patterns and cognitive performance. Finally, we discuss the possibilities of using these combined techniques to investigate the neural correlates of human creativity and to enhance creativity.

The cost-effectiveness of deep brain stimulation in combination with best medical therapy, versus best medical therapy alone, in advanced Parkinson’s disease

Parkinson’s disease (PD) is a complex progressive movement disorder leading to motor and non-motor symptoms that become increasingly debilitating as the disease advances, considerably reducing quality of life. Advanced treatment options include deep brain stimulation (DBS). While clinical effectiveness of DBS has been demonstrated in a number of randomised controlled trials (RCT), evidence on cost-effectiveness is limited. The cost-effectiveness of DBS combined with BMT, versus BMT alone, was evaluated from a UK payer perspective. Individual patient-level data on the effect of DBS on PD symptom progression from a large 6-month RCT were used to develop a Markov model representing clinical progression and capture treatment effect and costs. A 5-year time horizon was used, and an incremental cost-effectiveness ratio (ICER) was calculated in terms of cost per quality-adjusted life-years (QALY) and uncertainty assessed in deterministic sensitivity analyses. Total discounted costs in the DBS and BMT groups over 5 years were £68,970 and £48,243, respectively, with QALYs of 2.21 and 1.21, giving an incremental cost-effectiveness ratio of £20,678 per QALY gained. Utility weights in each health state and costs of on-going medication appear to be the key drivers of uncertainty in the model. The results suggest that DBS is a cost-effective intervention in patients with advanced PD who are eligible for surgery, providing good value for money to health care payers.

Exploration and modulation of brain network interactions with noninvasive brain stimulation in combination with neuroimaging.

Much recent work in systems neuroscience has focused on how dynamic interactions between different cortical regions underlie complex brain functions such as motor coordination, language and emotional regulation. Various studies using neuroimaging and neurophysiologic techniques have suggested that in many neuropsychiatric disorders, these dynamic brain networks are dysregulated. Here we review the utility of combined noninvasive brain stimulation and neuroimaging approaches towards greater understanding of dynamic brain networks in health and disease. Brain stimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation, use electromagnetic principles to alter brain activity noninvasively, and induce focal but also network effects beyond the stimulation site. When combined with brain imaging techniques such as functional magnetic resonance imaging, positron emission tomography and electroencephalography, these brain stimulation techniques enable a causal assessment of the interaction between different network components, and their respective functional roles. The same techniques can also be applied to explore hypotheses regarding the changes in functional connectivity that occur during task performance and in various disease states such as stroke, depression and schizophrenia. Finally, in diseases characterized by pathologic alterations in either the excitability within a single region or in the activity of distributed networks, such techniques provide a potential mechanism to alter cortical network function and architectures in a beneficial manner.

Effect of prefrontal transcranial magnetic stimulation on spontaneous truth-telling

Brain-process foundations of deceptive behaviour have become a subject of intensive study both in fundamental and applied neuroscience. Recently, utilization of transcranial magnetic stimulation has enhanced methodological rigour in this research because in addition to correlational studies causal effects of the distinct cortical systems involved can be studied. In these studies, dorsolateral prefrontal cortex has been implied as the brain area involved in deceptive behaviour. However, combined brain imaging and stimulation research has been concerned mostly with deceptive behaviour in the contexts of mock thefts and/or denial of recognition of critical objects. Spontaneous, “criminally decontextuated” propensity to lying and its dependence on the activity of selected brain structures has remained unexplored. The purpose of this work is to test whether spontaneous propensity to lying can be changed by brain stimulation. Here, we show that when subjects can name the colour of presented objects correctly or incorrectly at their free will, the tendency to stick to truthful answers can be manipulated by stimulation targeted at dorsolateral prefrontal cortex. Right hemisphere stimulation decreases lying, left hemisphere stimulation increases lying. Spontaneous choice to lie more or less can be influenced by brain stimulation.

Noninvasive Brain Stimulation May Improve Stroke-Related Dysphagia

Treatment options for stroke-related dysphagia are currently limited. In this study, we investigated whether noninvasive brain stimulation in combination with swallowing maneuvers facilitates swallowing recovery in dysphagic stroke patients during early stroke convalescence. Fourteen patients with subacute unilateral hemispheric infarction were randomized to anodal transcranial direct current stimulation (tDCS) versus sham stimulation to the sensorimotor cortical representation of swallowing in the unaffected hemisphere over the course of 5 consecutive days with concurrent standardized swallowing maneuvers. Severity of dysphagia was measured using a validated swallowing scale, Dysphagia Outcome and Severity scale, before the first and after the last session of tDCS or sham. The effect of tDCS was analyzed in a multivariate linear regression model using changes in Dysphagia Outcome and Severity Scale as the outcome variable after adjusting for the effects of other potential confounding variables such as the National Institutes of Health Stroke Scale and Dysphagia Outcome and Severity scale scores at baseline, acute ischemic lesion volumes, patient age, and time from stroke onset to stimulation. Patients who received anodal tDCS gained 2.60 points of improvement in Dysphagia Outcome and Severity scale scores compared to patients in the sham stimulation group who showed an improvement of 1.25 points (P=0.019) after controlling for the effects of other aforementioned variables. Six out 7 (86%) patients in tDCS stimulation group gained at least 2 points of improvement compared with 3 out 7 (43%) patients in the sham group (P=0.107). Because brain stem swallowing centers have bilateral cortical innervations, measures that enhance cortical input and sensorimotor control of brain stem swallowing may be beneficial for dysphagia recovery.

Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson's disease: A pilot study

Combined deep brain stimulation of the subthalamic (STN) and pedunculopontine (PPN) nuclei has been recently proposed as surgical treatment of advanced Parkinson's disease. STN stimulation alone has been shown to provide selective improvement of the grammatical aspect of language. We studied five advanced Parkinson's disease patients who underwent combined deep brain stimulation (STN + PPN). Overall cognitive profile did not change. On the contrary, an interesting trend towards reduction of ungrammatical errors (particularly substitution of free and inflectional morphemes) was found when stimulating the STN, and also the PPN, when the STN was switched off. These findings replicate previous observations on the STN, and provide the rationale for further investigation of the role of the PPN in processing linguistic grammar.

Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke

Anodal transcranial direct current stimulation (tDCS) can transiently increase corticomotor excitability of intrinsic hand muscles and improve upper limb function in patients with chronic stroke. As a preliminary study, we tested whether increased corticomotor excitability would be similarly observed in muscles acting about the wrist, and remain present during robotic training involving active wrist movements, in six chronic stroke patients with residual motor deficit. Transcranial magnetic stimulation (TMS) generated motor evoked potentials (MEP) in the flexor carpi radialis (FCR) and provided a measure of corticomotor excitability and short-interval cortical inhibition (SICI) before and immediately after a period of tDCS (1 mA, 20 min, anode and TMS applied to the lesioned hemisphere), and robotic wrist training (1hr). Following tDCS, the same TMS current strength evoked an increased MEP amplitude (mean 168 +/- 22%SEM; p < 0.05), that remained increased after robot training (166 +/- 23%; p < 0.05). Conditioned MEPs were of significantly lower amplitude relative to unconditioned MEPs prior to tDCS (62 +/- 6%, p < 0.05), but not after tDCS (89 +/- 14%, p = 0.40), or robot training (91 +/- 8%, p = 0.28), suggesting that the increased corticomotor excitability is associated with reduced intracortical inhibition. The persistence of these effects after robotic motor training, indicates that a motor learning and retraining program can co-exist with tDCS-induced changes in cortical motor excitability, and supports the concept of combining brain stimulation with physical therapy to promote recovery after brain injury.

Neurobiology of Obsessive-Compulsive Disorder:Serotonin and Beyond

AbstractThe evidence for the involvement of the serotonergic system in the pathogenesis of obsessive-compulsive disorder (OCD) is circumstantial at best, despite being the focus for most pathophysiological research over the last 2 decades. This hypothesis was initially motivated by the observed differential efficacy of selective serotonin reuptake inhibitors in alleviating OCD symptoms. Direct evidence that serotonergic perturbations are implicated in the pathophysiology of OCD is still sparse. There is growing evidence, from both preclinical and clinical studies, that the dopamine system may also be involved in the pathogenesis of OCD, and that dopaminergic and serotonergic pathways play a role in the genesis and maintenance of obsessive-compulsive symptoms. The complex interactions between both systems, the phenotypic heterogeneity of the disorder, and the limitations of the available tests to probe both systems, make it as yet impossible to draw firm conclusions as to how these systems are implicated. Further studies with more selective pharmacologic agents and neurocognitive probes in humans, studies using deep brain stimulation in combination with neuroimaging, and the development of better animal models for OCD may further our understanding of this disabling condition.

Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation.

Rostad, H. Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation. Acta physiol. scand. 1973. 89. 154–168. The peripheral pathways by which the hypothalamus and mesencephalon influence the motility of the colon have been studied by combining brain stimulation and peripheral nerve sectioning, and by use of autonomic blocking agents. Excitatory colonic effects induced from the hypothalamic sympatho-inhibitory area with concomitant blood pressure falls were found to be mediated through the sympathetic lumbar colonic nerves, whereas excitatory responses with associated blood pressure rises were conveyed through the latter as well as through the parasympathetic pelvic nerves. On the other hand, the augmentatory colonic effects usually associated with blood pressure rise evoked from the mesencephalon were conveyed through the lumbar colonic nerves only. The responses through the lumbar colonic and pelvic nerves were blocked by guanethidine and atropine, respectively. The augmentatory colonic responses from the hypothalamic sympatho-inhibitory area were blocked by the beta-adrenergic blocking agent propranolol, whereas the effects from the other responsive hypothalamic areas, transmitted through the lumbar colonic nerves, were blocked by alpha-blocker (phenoxybenzaminc), but not by propranolol. This finding support the presence of alpha-excitatory receptors in the colonic wall. Inhibition of colonic motility induced by hypothalamic and mesencephalic stimulation, weir found to be mediated through the lumbar colonic as well as through the splanchnic nerves. The effects were blocked by guanethidine, and those from the responsive hypothalamic zones were also blocked by propranolol.

Excitation and inhibition during motor cortex stimulation: A combined transcranial brain stimulation and event-related fMRI study

Excitation and inhibition during motor cortex stimulation: A combined transcranial brain stimulation and event-related fMRI study

Effects of anxiolytic drugs on rewarding and aversive behaviors induced by intracranial stimulation.

In considering the characteristics of the action of anxiolytic drugs and their mechanism in the brain, it may be necessary not only to study the behavioral pharmacology but also to perform brain site research. In the present study, the action of anxiolytic drugs was examined with respect to various behaviors that were induced by stimulating the brain areas related to emotions such as reward (pleasure) or aversion in rats. First, the low rate of response in lateral hypothalamic self-stimulation behavior was induced by schedules of low current brain stimulation, variable interval (VI) and differential reinforcement of low rate (DRL). Anxiolytic drugs such as benzodiazepines facilitated these low-rate responses. The drug susceptibility was highest in the low current stimulation, lower in the VI stimulation, and lowest in the DRL stimulation schedules. Furthermore, it was found by the auto-titration method in intracranial self-stimulation behavior that anxiolytic drugs decreased the threshold of stimulation reward. Second, it was recognized using the decremental lever pressing (DLP) paradigm that anxiolytic drugs increased the threshold of aversive stimulation of mesencephalic dorsal central gray (DCG), and this increasing effect of the drug was antagonized by GABA receptor blockers such as biccuculline. Finally, it was examined whether or not the conflict situation is established by combining brain stimulation reward and aversion, such as foot-shock or DCG stimulation. As a result, the conflict behavior was established by combining not only the brain stimulation reward and foot-shock aversion, but also the brain stimulation reward and DCG stimulation aversion. Further anxiolytic drugs exhibited anti-conflict action in both situations. The susceptibility of anxiolytic drugs was higher with respect to the conflict behavior induced by intracranial reward and aversion than to that induced by the conventional method based on milk reward and foot-shock aversion. These results suggest that behavioral methods using brain stimulation can examine the mechanisms of direct drug action at the brain stimulation site. Indeed, in the present brain stimulation behavioral study, anxiolytic drugs such as benzodiazepines increased the stimulation threshold in lateral hypothalamic self-stimulation and inhibited the DCG aversive stimulation, thus resulting in an anticonflict action of the drugs.

The neural bases of aggression and rage in the cat

This paper considers some of the basic findings underlying the neural bases of aggression and rage in the cat. The two basic models considered in this paper include predatory attack behavior and defensive rage. Anatomical studies point to the importance of the perifornical lateral hypothalamus for predatory attack and the medial hypothalamus and dorsal half of the midbrain periaqueductal gray for defensive rage as critical regions for the integration and expression of these two forms of aggressive behavior. Other experiments point to the important role of limbic structures in modulating each of these responses. The modulating properties of limbic structures provide a basic for understanding how dysfunctions of the temporal lobe can result in marked changes in aggressivity in humans. To date, studies combining brain stimulation, neuroanatomical, and neurochemical procedures have begun to identify the likely neurotransmitters that are associated with the key pathway from the medial hypothalamus to the periaqueductal gray over which defensive rage behavior is mediated, as well as the efferent pathways of the amygdala which modulate this form of aggression. Excitatory amino acids that act upon NMDA receptors have been implicated as the neurotransmitter associated with the descending pathway from the medial hypothalamus to the periaqueductal gray. Regions of the amygdala that facilitate defensive rage include the basal complex, which projects to the periaqueductal gray and utilizes excitatory amino acids as a neurotransmitter, and the medial nucleus, which projects to the medial hypothalamus and utilizes substance P as a neurotransmitter. In contrast, an enkephalinergic pathway that arises from the central nucleus of amygdala and which projects to the periaqueductal gray has been shown to powerfully inhibit defensive rage behavior.

Visual pattern discrimination through interactions of neural networks: a combined electrical brain stimulation, brain lesion, and extracellular recording study inSalamandra salamandra

In freely movingSalamandra salamandra various brain sites (n = 33) were stimulated monopolarly via chronically implanted electrodes. Stimulation of the optic tectum mainly elicited prey-catching behavior (mean lower current threshold Ilt = 9 μA) and sometimes predator-avoidance behavior (Ilt = 28 μA). Stimulation of the caudal dorsal (Ilt = 27 μA) or rostral dorsal thalamus (Ilt = 26 μA) exclusively released avoidance movements, such as ipsiversive turning, running, or moving backward. Telencephalic stimulation (Ilt = 66 μA) activated backward-creeping, trunk-raising, or jaw-opening/closing. Brain lesions were produced inn = 64 fire salamanders either by anodal DC current, radiofrequency current, Kainic acid micro-injections, or micro-knife cuts. After ablation of the optic tectum, both visually guided prey-catching and predator-avoidance behaviors failed to occur. Unilateral lesions in the following prosencephalic brain areas caused a strong deficit of configurational prey-selection (‘disinhibition of prey-catching behavior’) and a failure of visual predator-avoidance behavior in response to stimuli moving in certain areas of the visual field: (i) caudal dorsal thalamus (entire contralateral visual field), (ii) rostral dorsal thalamus (frontal visual field of both eyes), and (iii) medial pallium (entire visual field of both eyes). Lesions in the lateral pallium led to a decrease in the threshold of visually guided predator-avoidance behavior. Action potentials were extracellularly recorded from single tectal T5 neurons in intact animals and following various prosencephalic lesions (i), (ii), or (iii). In all of then = 14 investigated neurons the same alteration of response properties was obtained, corresponding to the change in behavior. Recordings from a single prey-selective class T5(1) neuron pre and post DC coagulation in the ipsilateral caudal dorsal thalamus produced: an increase in the diameter of the excitatory receptive field (ERF) from ≈30 ° to ≈50 ° and a strong deficit in selectivity with regard to moving configurational visual stimuli.

Colonic Motility in the Cat IV. Peripheral Pathways Mediating the Effects Induced by Hypothalamic and Mesencephalic Stimulation

AbstractRostad, H. Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation. Acta physiol. scand. 1973. 89. 154–168.The peripheral pathways by which the hypothalamus and mesencephalon influence the motility of the colon have been studied by combining brain stimulation and peripheral nerve sectioning, and by use of autonomic blocking agents. Excitatory colonic effects induced from the hypothalamic sympatho‐inhibitory area with concomitant blood pressure falls were found to be mediated through the sympathetic lumbar colonic nerves, whereas excitatory responses with associated blood pressure rises were conveyed through the latter as well as through the parasympathetic pelvic nerves. On the other hand, the augmentatory colonic effects usually associated with blood pressure rise evoked from the mesencephalon were conveyed through the lumbar colonic nerves only. The responses through the lumbar colonic and pelvic nerves were blocked by guanethidine and atropine, respectively. The augmentatory colonic responses from the hypothalamic sympatho‐inhibitory area were blocked by the beta‐adrenergic blocking agent propranolol, whereas the effects from the other responsive hypothalamic areas, transmitted through the lumbar colonic nerves, were blocked by alpha‐blocker (phenoxybenzaminc), but not by propranolol. This finding support the presence of alpha‐excitatory receptors in the colonic wall. Inhibition of colonic motility induced by hypothalamic and mesencephalic stimulation, weir found to be mediated through the lumbar colonic as well as through the splanchnic nerves. The effects were blocked by guanethidine, and those from the responsive hypothalamic zones were also blocked by propranolol.

Effect of combined brain stimulation on gastric secretion, acidity and potassium concentration in cats

Hippocampectomized male rats were prepared, and the incidence as well as severity of gastric ulceration upon restraint were compared with those of normal control animals and controls with localized damage to the cortex over the hippocampus. In another experiment, observations on gastric ulceration were made without restraint in hippocampectomized animals, normal controls, controls with cortical damage, vagotomized animals and animals that received hippocampectomy as well as vagotomy.Both in restrained and unrestrained states, the incidence of animals with ulcer as well as the number and the total area of ulcers per stomach were significantly larger in the hippocampal animals than they were in the other animal groups. Vagotomy abolished the effect of hippocampectomy upon gastric ulceration in the unrestrained state.We infer that the hippocampus helps to protect the stomach from ulceration partly by controlling vagal activity.