Therapeutic potential of brain stimulation techniques in the treatment of mental,psychiatric, and cognitive disorders

Treatment for brain diseases has been disappointing because available medications have failed to produce clinical response across all the patients. Many patients either do not respond or show partial and inconsistent effect, and even in patients who respond to the medications have high relapse rates. Brain stimulation has been seen as an alternative and effective remedy. As a result, brain stimulation has become one of the most valuable therapeutic tools for combating against brain diseases. In last decade, studies with the application of brain stimulation techniques not only have grown exponentially but also have expanded to wide range of brain disorders. Brain stimulation involves passing electric currents into the cortical and subcortical area brain cells with the use of noninvasive as well as invasive methods to amend brain functions. Over time, technological advancements have evolved into the development of precise devices; however, at present, most used noninvasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In the current review, we will provide an overview of the potential of noninvasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques focusing on the treatment of mental, psychiatric, and cognitive disorders.     

Luteinizing hormone-releasing hormone and oxytocin response to hyperosmotic stimulation: in vitro study

It was shown previously that luteinizing hormone-releasing hormone (LHRH) affects the neurohypophysial oxytocin release in water-deprived rats. However, the detailed mechanisms by which LHRH modifies the oxytocin response to hyperosmotic stimulation have not been explained so far. Using the isolated hypothalamo-neurohypophysial explants obtained from euhydrated rats, the effect of LHRH on the oxytocin secretion was studied under conditions of direct osmotic (i.e., Na(+)- evoked) as well as nonosmotic (i.e., K(+)-evoked) stimulation. Additionally, the oxytocin response to LHRH was investigated using the explants obtained from animals drinking 2% saline for eight days (systemic, i. e., both direct and indirect, osmotic stimulation). LHRH significantly enhanced Na(+)- and K(+)-evoked oxytocin release from explants taken from rats drinking tap water, indicating that LHRH could affect the Na(+)/K(+)-dependent depolarization of perikarya of oxytocin neurones. In contrast, LHRH significantly diminished the K(+)-stimulated hormone release when the neurohypophysial complex was obtained from previously salt-loaded rats, suggesting that peripheral osmotic stimulation somehow modifies the sensitivity of oxytocinergic neurones to LHRH (possible mechanisms are discussed). It is concluded that LHRH may participate in the regulation of oxytocin secretion via both direct and indirect impact on magnocellular oxytocinergic neurones depending on the current functional status of the hypothalamo-neurohypophysial complex.     

Evidence for peripheral, but not central modulation of trigeminal cold receptive cells in the rat

The effects of locus coeruleus (LC), periaqueductal grey (PAG) and segmental stimulation (all of which are known to inhibit convergent nociceptive cells), were tested on the activity of cold receptive cells in the trigeminal system of the rat. LC and PAG stimulation from sites which inhibited convergent nociceptive cells had no effect on cells with cold receptive input in the trigeminal nucleus caudalis. Electrical or mechanical segmental stimulation caused suppression of activity in cold receptive trigeminal nucleus neurons. Recording from the trigeminal ganglion showed this suppression to be a property of the primary afferent cold receptors themselves and therefore it is not analogous to the proposed mechanism for the segmental inhibition of convergent nociceptive neurons.     

神经调控技术治疗抽动秽语综合征研究进展

抽动秽语综合征是一种通常在儿童期起病,以运动及发生抽动为特点的慢性复杂性神经精神疾病,常伴有行为和精神症状,如强迫观念与行为、注意缺陷多动障碍、学习困难、情绪障碍、自伤和猥亵行为等。     

Challenges of proper placebo control for non‐invasive brain stimulation in clinical and experimental applications

A range of techniques are now available for modulating the activity of the brain in healthy people and people with neurological conditions. These techniques, including transcranial magnetic stimulation (TMS) and transcranial current stimulation (tCS, which includes direct and alternating current), create magnetic or electrical fields that cross the intact skull and affect neural processing in brain areas near to the scalp location where the stimulation is delivered. TMS and tCS have proved to be valuable tools in behavioural neuroscience laboratories, where causal involvement of specific brain areas in specific tasks can be shown. In clinical neuroscience, the techniques offer the promise of correcting abnormal activity, such as when a stroke leaves a brain area underactive. As the use of brain stimulation becomes more commonplace in laboratories and clinics, we discuss the safety and ethical issues inherent in using the techniques with human participants, and we suggest how to balance scientific integrity with the safety of the participant.     

Calcium-dependent release of endogenous glutamate from vascularly perfused rat stomach in vitro

To investigate a possible physiological role for glutamate in the stomach, release of endogenous glutamate from an isolated vascularly-perfused rat stomach preparation was studied. Glutamate was measured by the bioluminescence assay method. High concentrations of KCl (30–75 mM) induced a dose-dependent release of glutamate. This KCl-induced release of glutamate was abolished in calcium-free medium containing ethylene glycol bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA). Electrical stimulation of the vagus nerves also induced a release of glutamate. This vagal stimulation-induced release of glutamate was abolished by both calcium removal and tetrodotoxin (TTX). Amounts of 13 other amino acids in the medium, detectable by the automatic amino-acid analyzer, were not significantly affected by both high-K⁺ and the vagal stimulation. These results provide additional evidence that glutamate probably serves as a neurotransmitter in the stomach. © 1996 Wiley-Liss, Inc.     

功能性电刺激结合重复经颅磁刺激用于缺血性脑卒中偏瘫患者步行障碍恢复的临床观察

目的 观察功能性电刺激结合重复经颅磁刺激用于缺血性脑卒中偏瘫患者步行障碍恢复的临床疗效。方法 将53例缺血性脑卒中偏瘫患者随机分为对照组、治疗组、假治疗组3组,在均接受常规康复训练的基础上对照组接受功能性电刺激治疗,治疗组接受功能性电刺激及重复经颅磁刺激治疗,假治疗组接受功能性电刺激及假重复经颅磁刺激治疗; 治疗前及治疗8周后采用步态运动学参数、时间参数、距离参数及Amer-Lindholm分级对3组患者的下肢综合运动功能进行评定。结果 治疗前3组患者步态运动学参数、时间参数、距离参数及Amer-Lindholm分级评分均无显著差异(P>0.05),治疗8周后3组患者上述指标明显改善且治疗组改善幅度明显优于其余2组(P<0.05)。结论 功能性电刺激联合重复经颅磁刺激治疗有利于改善缺血性脑卒中偏瘫患者的步行运动功能。     

Peripheral Subcutaneous Neurostimulation in the Management of Neuropathic Pain: Five Case Reports

Introduction. Spinal cord stimulation (SCS) is an effective treatment option for neuropathic pain. However, because of the obvious procedural issues, SCS is unable to reach certain areas, such as the face, thorax, coccyx, the cervico‐dorsal and lumbar areas, and the sacral, abdominal, and inguinal regions. On the other hand, these areas are easily reached by subcutaneous field stimulation. Methodology. We report the analgesic results, using a visual analog scale (VAS), of five patients with neuropathic pain treated with subcutaneous field stimulation to the area. We also discuss the probable mechanism of action, and highlight the technical issues inherent to this approach. Results. Significant pain reduction and reduction in analgesic medication were reported in all patients during the study period, with VAS scores consistently lowered by more than 50% from baseline levels. As a result of pain reduction, the patients’ quality of life improved. There were no adverse events reported except for early electrode array displacement in two of our patients. Conclusion. When SCS is not appropriate for certain neuropathic pain syndromes, subcutaneous field stimulation may be used with some degree of efficacy.     

Functional involvement of cerebral cortex in duchenne muscular dystrophy

Transcranial stimulation was performed in 4 patients with Duchenne muscular dystrophy and 4 control subjects. The patients' central motor conduction time was normal. The threshold for evoking electromyographic responses using electrical anodal stimulation was the same in both groups, but the threshold for stimulation with a circular magnetic coil at the vertex was higher in the patients. This is compatible with reduced cortical excitability that may be related to the deficiency of brain synaptic dystrophin. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:662–664, 1998.     

Pallidal deep brain stimulation in the treatment of Meige syndrome

IntroductionMeige syndrome (MS) is characterized by blepharospasm, facial, oromandibular, and often cervical dystonia. The medical treatment of this condition is challenging and unsuccessful over long time. Recent case reports and small clinical series showed that bilateral deep brain stimulation (DBS) of globus pallidus pars interna (GPi) improves dystonic features of MS validated by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).Materials and methodsWe report on our experience in using bilateral GPi DBS in 3 cases of MS. We present short-term (3 months) follow-up as well long-term (from 8 months to 36 months) results.Preoperative and postoperative BFMDRS assessments were performed on each patient. The postoperative BFMDRS scores was done when both stimulators were switched on and compared to baseline scores.ResultsBilateral GPi DBS reduced the BFMDRS total movement score by 66% at short-term follow-up, and by 75% at long-term follow-up when compared to baseline scores. The BFMDRS total disability score was reduced by 34% at short-term follow-up, and by 47% at long-term follow-up when compared to baseline scores.ConclusionsOur results showed that bilateral GPi DBS in MS is effective and safe, if conservative treatment options failed. The benefit is not only observed at short-term 3 months period but is maintained at long-term follow-up ranging from 8 to 36 months.     

Cerebellar Modulation of Sensorimotor Associative Plasticity Is Impaired in Cervical Dystonia

Background

In recent years, cervical dystonia (CD) has been recognized as a network disorder that involves not only the basal ganglia but other brain regions, such as the primary motor and somatosensory cortex, brainstem, and cerebellum. So far, the role of the cerebellum in the pathophysiology of dystonia is only poorly understood.

Objective

The objective of this study was to investigate the role of the cerebellum on sensorimotor associative plasticity in patients with CD.

Methods

Sixteen patients with CD and 13 healthy subjects received cerebellar transcranial direct current stimulation (ctDCS) followed by a paired associative stimulation (PAS) protocol based on transcranial magnetic stimulation that induces sensorimotor associative plasticity. Across three sessions the participants received excitatory anodal, inhibitory cathodal, and sham ctDCS in a double-blind crossover design. Before and after the intervention, motor cortical excitability and motor symptom severity were assessed.

Results

PAS induced an increase in motor cortical excitability in both healthy control subjects and patients with CD. In healthy subjects this effect was attenuated by both anodal and cathodal ctDCS with a stronger effect of cathodal stimulation. In patients with CD, anodal stimulation suppressed the PAS effect, whereas cathodal stimulation had no influence on PAS. Motor symptom severity was unchanged after the intervention.

Conclusions

Cerebellar modulation with cathodal ctDCS had no effect on sensorimotor associative plasticity in patients with CD, in contrast with the net inhibitory effect in healthy subjects. This is further evidence that the cerebello-thalamo-cortical network plays a role in the pathophysiology of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Cortical oscillatory activity and the induction of plasticity in the human motor cortex

Repetitive transcranial magnetic stimulation paradigms such as continuous theta burst stimulation (cTBS) induce long-term potentiation- and long-term depression-like plasticity in the human motor cortex. However, responses to cTBS are highly variable and may depend on the activity of the cortex at the time of stimulation. We investigated whether power in different electroencephalogram (EEG) frequency bands predicted the response to subsequent cTBS, and conversely whether cTBS had after-effects on the EEG. cTBS may utilize similar mechanisms of plasticity to motor learning; thus, we conducted a parallel set of experiments to test whether ongoing electroencephalography could predict performance of a visuomotor training task, and whether training itself had effects on the EEG. Motor evoked potentials (MEPs) provided an index of cortical excitability pre- and post-intervention. The EEG was recorded over the motor cortex pre- and post-intervention, and power spectra were computed. cTBS reduced MEP amplitudes; however, baseline power in the delta, theta, alpha or beta frequencies did not predict responses to cTBS or learning of the visuomotor training task. cTBS had no effect on delta, theta, alpha or beta power. In contrast, there was an increase in alpha power following visuomotor training that was positively correlated with changes in MEP amplitude post-training. The results suggest that the EEG is not a useful state-marker for predicting responses to plasticity-inducing paradigms. The correlation between alpha power and changes in corticospinal excitability following visuomotor training requires further investigation, but may be related to disengagement of the somatosensory system important for motor memory consolidation.     

Behavioural recovery following transplantation of substantia nigra in rats subjected to 6-OHDA lesions of the nigrostriatal pathway. II. Bilateral lesions

Rats with a unilateral transplant of embryonic substantia nigra, placed in a cortical cavity overlying the caudate-putamen, were compared with control animals on a range of behavioral tests following bilateral 6-OHDA lesions of the ascending dopaminergic nigrostriatal pathway. Tests designed to reveal behavioural asymmetry--such as spontaneous, tail-pinch and amphetamine-induced rotation, sensorimotor orientation, and side preference in a T-maze--revealed that the rats with bilateral 6-OHDA lesions and a unilateral transplant are similar to unilaterally lesioned animals with one intact nigrostriatal pathway. Both transplanted and bilaterally lesioned control rats became spontaneously akinetic after the second 6-OHDA lesion. This akinesia could be reversed by a low dose of amphetamine (0.5 mg/kg) in the transplanted but not in the non-transplanted control rats. The attenuated effects of apomorphine and L-DOPA on activity and rotation suggest that the nigral transplant produced a partial reversal of receptor supersensitivity following the 6-OHDA lesion on the same side as the transplant. However, other effects of the bilateral 6-OHDA lesion, including the development of aphagia, adipsia and akinesia, were not reversed by the presence of the transplant. The transplants were shown by fluorescence histochemistry to have densely reinnervated the dorsal parts of the denervated caudateputamen on the side ipsilateral to the transplant. The results show that intracortical nigral grafts reinnervating parts of the dorsal caudate-putamen can reverse some, but not all, functional impairments associated with bilateral destruction of the nigrostriatal pathway.     

Non‐invasive magnetic stimulation of the human cerebellum facilitates cortico‐bulbar projections in the swallowing motor system

Background Animal and human brain imaging studies suggest that the cerebellum plays an important role in the control of swallowing. In this study, we probed the interaction between cerebellar and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can modulate cortical swallowing motor circuitry. Methods Healthy volunteers (n = 16, eight men, mean age = 32, range 19–57 years) underwent TMS measurements of pharyngeal electromyography (EMG) recorded from a swallowed intraluminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm, where active or sham TMS conditioning pulses over the cerebellum and control sites were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at varying inter‐stimulus intervals (ISIs) with the cortical response amplitudes being assessed. Key Results Stimulation of the cerebellum over its midline or hemispheres evoked distinct pharyngeal EMG responses. There was no difference in EMG amplitudes following cerebellar hemispheric or midline stimulation (mean 55.5 ± 6.9 vs 42.8 ± 5.9 μV, P = 0.08). In contrast, after cerebellar preconditioning, the cortically evoked responses underwent maximal facilitation at ISIs of 50–200 ms (P < 0.05), an effect not seen with sham or trigeminal nerve preconditioning. Conclusions & Inferences Posterior fossa stimulation excites the cerebellum and evokes direct motor responses within the pharynx. When conditioned with TMS, the cerebellum strongly facilitates the cortical swallowing motor pathways. This finding suggests that the cerebellum exerts a modulatory effect on human swallowing and raises the possibility that excitatory neurostimulation of the cerebellum may be therapeutically useful in promoting recovery of dysphagia after neural damage.     

Brain stimulation: a therapeutic approach for the treatment of neurological disorders

Brain stimulation has become one of the most acceptable therapeutic approaches in recent years and a powerful tool in the remedy against neurological diseases. Brain stimulation is achieved through the application of electric currents using non-invasive as well as invasive techniques. Recent technological advancements have evolved into the development of precise devices with capacity to produce well-controlled and effective brain stimulation. Currently, most used non-invasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In last decade, application of these brain stimulation techniques has not only exploded but also expanded to wide variety of neurological disorders. Therefore, in the current review, we will provide an overview of the potential of both non-invasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques in the treatment of such brain diseases.     

Neurostimulation therapies in depression: a review of new modalities

OBJECTIVE: In response to an increased understanding of the neurobiology of severe psychiatric disorders, new therapeutic modalities are entering clinical practice that involve the direct stimulation of the brain. METHOD: We provide a review of published literature regarding the clinical use of vagus nerve stimulation (VNS) therapy, transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) in psychiatric disorders, with an emphasis on treatment-resistant depression (TRD). RESULTS: Vagus nerve stimulation is approved for use in both the EU and US for TRD. TMS has been approved for TRD in Canada, Australia, New Zealand, the European Union and Israel, but not yet in the United States. DBS remains in the early stages of investigation. CONCLUSION: While additional studies are clearly warranted, treatments that directly stimulate the brain appear to hold great therapeutic promise for severe psychiatric disorders.     

Preferential activation of muscle fibers with peripheral magnetic stimulation of the limb

Magnetic and electric activation of limb nerve and muscle were compared in normal subjects of different age, gender, and habitus. Direct stimulation of nerve and muscle showed that activation of intramuscular nerve fibers in the arm and leg occurs at a lower threshold for magnetic stimulation than for electric stimulation. Sensory nerve fibers had a lower threshold with electric stimulation. Muscle activation and stimulus artifact with magnetic stimulation precluded reliable recording of distal sensory nerve action potential in all subjects.