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.     

Non-invasive electrical brain stimulation: from acute to late-stage treatment of central nervous system damage

Non-invasive brain current stimulation(NIBS) is a promising and versatile tool for inducing neuroplasticity,protection and functional rehabilitation of damaged neuronal systems.It is technically simple,requires no surgery,and has significant beneficial effects.However,there are various technical approaches for NIBS which influence neuronal networks in significantly different ways.Transcranial direct current stimulation(t DCS),alternating current stimulation(ACS) and repetitive transcranial magnetic stimulation(r TMS) all have been applied to modulate brain activity in animal experiments under normal and pathological conditions.Also clinical trials have shown that t DCS,r TMS and ACS induce significant behavioural effects and can – depending on the parameters chosen – enhance or decrease brain excitability and influence performance and learning as well as rehabilitation and protective mechanisms.The diverse phaenomena and partially opposing effects of NIBS are not yet fully understood and mechanisms of action need to be explored further in order to select appropriate parameters for a given task,such as current type and strength,timing,distribution of current densities and electrode position.In this review,we will discuss the various parameters which need to be considered when designing a NIBS protocol and will put them into context with the envisaged applications in experimental neurobiology and medicine such as vision restoration,motor rehabilitation and cognitive enhancement.     

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.     

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation ( P  = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.     

Noninvasive Brain Stimulation to Modulate Neuroplasticity in Traumatic Brain Injury

Objective: To review the use of noninvasive brain stimulation (NBS) as a therapeutic tool to enhance neuroplasticity following traumatic brain injury (TBI). Materials and Methods: Based on a literature search, we describe the pathophysiological events following TBI and the rationale for the use of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in this setting. Results: The pathophysiological mechanisms occurring after TBI vary across time and therefore require differential interventions. Theoretically, given the neurophysiological effects of both TMS and tDCS, these tools may: 1) decrease cortical hyperexcitability acutely after TBI; 2) modulate long‐term synaptic plasticity as to avoid maladaptive consequences; and 3) combined with physical and behavioral therapy, facilitate cortical reorganization and consolidation of learning in specific neural networks. All of these interventions may help decrease the burden of disabling sequelae after brain injury. Conclusions: Evidence from animal and human studies reveals the potential benefit of NBS in decreasing the extent of injury and enhancing plastic changes to facilitate learning and recovery of function in lesioned neural tissue. However, this evidence is mainly theoretical at this point. Given safety constraints, studies in TBI patients are necessary to address the role of NBS in this condition as well as to further elucidate its therapeutic effects and define optimal stimulation parameters.     

Repetitive transcranial magnetic stimulation in treatment of post polio syndrome

Background

Post polio syndrome is a rare disease that occurs decades after polio virus infection. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness in drug resistant depression. Possibly it can be helpful in therapy of other neurological diseases including post polio syndrome.

Transcranial magnetic stimulation in the treatment of psychiatric disorders

Transcranial magnetic stimulation (TMS) is a new technology that applies the principles of electromagnetism to deliver an electrical field to the cerebral cortices. Well established in diagnostic electrophysiology, TMS is now being studied as a treatment for psychiatric disorders. Evidence suggests this technique is safe and acceptable to patients. The future may see the application of TMS in obsessive-compulsive disorder, post-traumatic stress disorder and mania. There is strong evidence that it will become an accepted treatment of depression.     

重复经颅磁刺激治疗迟发性运动障碍患者的疗效观察

目的:观察重复经颅磁刺激( rTMS)对慢性精神分裂症迟发性运动障碍(TD)患者的治疗效果.方法:运用rTMS对36例慢性精神分裂症TD患者进行治疗,共12周,用异常不自主运动量表( AIMS)评估. 结果:rTMS对TD患者的显效率为56.5％,治疗后AIMS评分显著下降[基线(9.1±2.8)分,治疗以后(3.4±...     

rTMS as a treatment for neurogenic communication and swallowing disorders

Recent years have seen the introduction of non‐invasive brain stimulation techniques (e.g. transcranial direct current stimulation and transcranial magnetic stimulation) utilized to target neural‐based pathologies, for therapeutic gain. The direct manipulation of cortical brain activity by repetitive transcranial magnetic stimulation (rTMS) could potentially serve as an efficacious complimentary rehabilitatory treatment for speech, language and swallowing disorders of a neurological origin. The high prevalence of positive reports on communication and swallowing outcomes support these premises. Nonetheless, experimental evidence to date in some areas is considered rudimentary and is deficient in providing placebo‐controlled substantiation of longitudinal neuroplastic change subsequent to stimulation. The most affirmative therapeutic responses have arisen from small placebo‐controlled trials using low‐frequency rTMS for patients with non‐fluent aphasia and high‐frequency rTMS applied to individuals with Parkinson's disease to improve motor speech performance and outcomes. Preliminary studies applying rTMS to ameliorate dysphagic symptoms post‐stroke provide positive swallowing outcomes for patients. Further research into the optimization of rTMS protocols, including dosage, stimulation targets for maximal efficacy and placebo techniques, is critically needed to provide a fundamental basis for clinical interventions using this technique. rTMS represents a highly promising and clinically relevant technique, warranting the future development of clinical trials across a spectrum of communication and swallowing pathologies, to substantiate and expand on the methods outlined in published reports.     

Motor Cortex Stimulation for Pain: A Narrative Review of Indications,Techniques, and Outcomes

BackgroundMotor cortex stimulation (MCS) was introduced in 1985 and has been tested extensively for different types of peripheral and central neuropathic pain syndromes (eg, central poststroke pain, phantom limb pain, trigeminal neuropathic pain, migraines, etc). The motor cortex can be stimulated through different routes, including subdural, epidural, and transcranial.ObjectivesIn this review, we discuss the current uses, surgical techniques, localization techniques, stimulation parameters, and clinical outcomes of patients who underwent chronic MCS for treatment-resistant pain syndromes.Materials and MethodsA broad literature search was conducted through PubMed to include all articles focusing on MCS for pain relief (keywords: subdural, epidural, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, motor cortex stimulation, pain).Literature ReviewEpidural MCS was the most widely used technique and had varying response rates across studies. Long-term efficacy was limited, and pain relief tended to decrease over time. Subdural MCS using similar stimulation parameters demonstrated similar efficacy to epidural stimulation and less invasive methods, such as repetitive transcranial magnetic stimulation (rTMS), which have been shown to provide adequate pain relief. rTMS and certain medications (ketamine and morphine) have been shown to predict the long-term response to epidural MCS. Complications tend to be rare, the most reported being seizures during subdural or epidural stimulation or hardware infection.ConclusionsScientific evidence supports the use of MCS for treatment of refractory neuropathic pain syndromes. Further studies are warranted to elucidate the specific indications and stimulation protocols that are most amenable to the different types of MCS.     

Transcranial direct current stimulation for the treatment of focal hand dystonia

The treatment of writer's cramp, a task‐specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double‐blind, sham‐controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2‐week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. © 2011 Movement Disorder Society     

Exploring Patient Perceptions of Noninvasive Brain Stimulation: A Systematic Review

ObjectiveTo synthesize and critically appraise literature exploring patient perceptions regarding the therapeutic use of noninvasive brain stimulation.Material and MethodsA systematic search of CINHAL, PUBMED, Web of Science, and Medline was performed. Reference lists of relevant articles were also screened. Studies exploring participant perceptions regarding the therapeutic use of noninvasive brain stimulation were eligible for inclusion. Perceptions were divided into three domains: knowledge, experience, and attitudes. Noninvasive brain stimulation was defined as any neuromodulation technique that alters brain activity but does not require invasive methods such as surgery. No restrictions were placed upon study design or participant population. Two reviewers performed data extraction and risk of bias assessment. Data relating to methodological characteristics, participant demographics, type of noninvasive brain stimulation, and nature of perceptions (knowledge, experience, or attitudes) were extracted.ResultsFour studies comprising data from 163 participants met the inclusion criteria. All studies investigated perceptions of repetitive transcranial magnetic stimulation (rTMS) in psychiatric populations. Most participants perceived rTMS to be safe and beneficial, demonstrated low levels of fear, and were willing to recommend the intervention to others. No studies were found investigating patient perception of transcranial direct current stimulation (tDCS).ConclusionThe findings from this review suggest that rTMS is well accepted as a therapeutic treatment among psychiatric populations, providing support for its clinical utility. Future work is needed to determine if similar findings exist for other conditions (eg, chronic pain) and for other therapeutic forms of brain stimulation (eg, tDCS).     

Noninvasive brain stimulation combined with other therapies improves gait speed after stroke: a systematic review and meta-analysis

Background: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive brain stimulation (NIBS) techniques able to modulate cortical excitability.

Objective: To determine the effects of NIBS combined with other therapies on gait speed after stroke.

Methods: Electronic databases searched were PUBMED, EMBASE, COCHRANE, SCOPUS, SCIELO and PEDro. Eligibility criteria were randomized controlled trials that reported the effects of tDCS and rTMS combined with other therapies for improving gait speed, walking cadence, functional ambulation category (FAC) and motricity index (MI-LE) after stroke. Risk of bias was assessed by Cochrane risk of bias assessment tool. Mean differences (MD) and 95% confidence intervals were calculated. Quality of evidence was assessed by Grades of Researches, Assessment, Development and Evaluation approach.

Results: Ten studies (226 subjects) were included in the meta-analysis. NIBS combined with other therapies was effective for improving gait speed (MD 0.09 m/s [95% CI, 0.05 to 0.13; I² 0%, p < 0.0001]). Gait speed improved in both acute/subacute (MD 0.08 m/s [95% CI, 0.02 to 0.14]) and chronic phases (MD 0.08 m/s [95% CI, 0.03 to 0.13]). Furthermore, inhibitory (MD 0.09 m/s [95% CI, 0.04 to 0.14]) and excitatory (MD 0.07 m/s [95% CI, 0.02 to 0.12]) protocols were effective to improve gait speed. NIBS was also effective to improve walking cadence but was unable to modify other outcomes (FAC and MI-LE).

Conclusions: This systematic review with meta-analysis synthesizes moderate-quality evidence that NIBS combined with other therapies are effective to improve gait speed after stroke.

Systematic Review registration number: PROSPERO registration number CDR42015024237.     

Motor cortex stimulation for levodopa-resistant akinesia: case report.

We treated a patient with levodopa-resistant akinesia with motor cortex stimulation (MCS), and she showed dramatic improvement more than 1 year. On admission, the patient presented severe akinesia and gait disturbance without tremor and rigidity, and did not respond to levodopa test. The patient was suspected pure akinesia and progressive supranuclear palsy. First, high-frequency rTMS of primary motor cortex was examined, and showed the dramatic improvement. Next, chronic subdural electrodes were implanted over the motor cortex bilaterally. One year after surgery, the Unified Parkinson's Disease Rating Scale had improved remarkably, and she could walk four times faster than before. The H2 15O PET study showed a significant increase of rCBF in the left SMA and right dorsolateral prefrontal cortex after bilateral MCS. MCS may be an alternative treatment for patients with akinesia, including those with PD, and particularly for levodopa-resistant patients, who respond well to rTMS.     

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy

Objectives:  Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
Methods:  We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Results:  Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 – 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks ( t =−0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t =1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment ( t =1.11, p=0.28).
Conclusions:  Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.