The applications of neurophysiological therapy techniques range far and few in the realm of modern day medicine. However, the concept of electromagnetic stimulation, the basis for many noninvasivebrainstimulation (NIBS) techniques today, has been of interest to the scientific community since the late nineteenth century. Recently, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), two noninvasive neurostimulation techniques, have begun to gain popularity and acceptance in the clinical neurophysiology, neurorehabilitaion, neurology, neuroscience, and psychiatry has spread widely, mostly in research applications, but increasingly with clinical aims in mind. These two neurophysiological techniques have proven to be valuable assets in not only the diagnosis, but also the treatment of many neurological disorders (post-stroke motor deficits, tinnitus, fibromyalgia, depression, epilepsy, autism, ageing and parkinson’s disease). Its effects can be modulated by combination with pharmacological treatment that has undergone resurgence in recent years. In this review we discuss how these integrated technology like NIBS for evaluation in the clinical evidence to date and what mechanism it work for stroke rehabilitation particularly. Then, we will review the current situation of stroke rehabilitation in Iran and new hopes that NIBS could bring for clinicians and patients in this nationally prioritized field.
patients after stroke is essential for independent activities of daily living, The upper limbs contribute to most ctivities of daily living We designed this randomized double-blind, sham-controlled trial to examine the effect of two noninvasivebrainstimulation techniques on recovery of functions in the upper limbs after stroke. Methods: Forty- two chronic hemiplegic stroke patients were randomly allocated across 3 groups to undergo 24 sessions, 3d/wk of intervention combined with standard physiotherapy for motor functions of upper limb, Group (A) comprised 18 subjects who received 1-Hz rTMS, Group B comprised 13 subjects who received tDCS. Group C comprised 11 subjects who received Sham1-Hz rTMS.. Outcome measures were assessed by the Fugl-Meyer assessment (FMA)., grip strength, and stroke-specific quality-of life scale. at the baseline and after intervention. Results: Significant improvement from baseline was noted following intervention in rTMS and tDCS groups, in the FMA, and SSQOL in upper limb motor functions. The rTMS group showed significantly improvements than the other two groups in handgrip strength. Conclusions: Noninvasivebrainstimulation combined with standard physiotherapy can be more beneficial in improving upper limb functions after stroke,
Although this was an open-label, naturalistic study conducted on a small number of patients, it was the first study to explore the potential of brainstimulation in a clinical disorder such as agoraphobia, a disorder with no clear organic framework. The refractory nature of agoraphobia to current treatments, combined with the great suffering and progressive functional impairment of patients, necessitates development of new therapeutic strategies to promote social rehabilitation. The unique, noninvasivebrainstimulation achieved by REAC appears very promising because of its high tolerability and good safety profile.
The effects of noninvasivebrainstimulation procedures, such as tDCS, on athletic performance have been investigated in several studies. tDCS delivers a low-intensity constant cur- rent, usually between 1 and 2 mA, via electrodes that are applied on the participant’s scalp above brain regions of inter- est for a variable amount of time (usually for 5 to 20 min). A portion of the applied current penetrates the brain and is ef- fective in altering spontaneous neural activity and excitability (Nitsche et al. 2008). The current applied to the brain through tDCS is not sufficiently strong to generate action potentials (Nitsche et al. 2008). Indeed, tDCS induces a sub-threshold modulation of the resting membrane potential of cortical neu- rons, changing their likelihood of firing and consequently impacting spontaneous cortical activity (Nitsche and Paulus 2000; Nitsche et al. 2003a, 2008). The tDCS-induced changes in the resting membrane potential are for the most part regu- lated by the polarity of the stimulation. Anodal stimulation induces a slight depolarization of the resting membrane po- tential, most likely at the soma and axon of the targeted neu- rons, which raises the probability of neural firing and, accord- ingly, cortical excitability (Nitsche and Paulus 2000). In con- trast, cathodal stimulation causes a slight hyperpolarization of the resting membrane potential of respective structures and thereby reduces the probability of neural firing and excitability (Nitsche and Paulus 2000). Shifts in neural activity take place during the stimulation period as well as after the stimulation period, if the current is delivered for a sufficient period of time (i.e., at least 9–10 min). Such shifts can last for longer than 1 h after the stimulation has ended and are assumed to resemble plasticity of glutamatergic synapses (Nitsche and Paulus 2000; Nitsche et al. 2003a, 2008).
However, a real efficacy of TMS on motor cortex in PD is controversial since subsequent studies show contradictory results. 12 TMS a non-invasive means of stimulating neurons in the human cerebral cortex, is able to modify neuronal activity locally and at distant sites when delivered in series or trains of pulses. 13 Previous studies have demonstrated the potential modulatory effects of repetitive transcranial magnetic stimulation (rTMS) on the excitability of cortical neurons 14 and this effect depends on the parameters used in the stimulation such as intensity, frequency, site of stimulation, and can last beyond the duration of the rTMS. 15 After rTMS, glucose metabolism assessed using with Positron emission tomography (PET) was increased at the stimulation site and in both distant contralateral M1 and supplementary motor area (SMA), 16 also, induce dopamine release in the ventrolateral putamen and caudate. 17 TMS given either continuously at a low frequency (0.2-1 Hz) or in intermittent trains at higher frequencies(5-20 Hz). Circular TMS coils induce cortical currents that span at least the diameter of the coil; they are therefore less specific than more focal figure-8 coils which also provide the ability to target specific cortical regions. 18
Chronic progressive diseases are a challenge for NBS. The evolution of these diseases occurs over the longer-term and is constantly changing, whereas NBS is difficult to administer chronically and probably does not have the flexibility to manage a constantly changing baseline. Par- kinson's disease (PD) is a progressively developing move- ment disorder arising from loss of dopaminergic neurons in the substantia nigra and depletion of dopamine in the basal ganglia. Although the pathology is subcortical, sec- ondary abnormalities manifest in cortical structures, including changes in cortical inhibition and shifts in the cortical representation of hand muscles which can occur in both early and late stages of the disease [24,25]. Map shifts correlate with the severity of clinical symptoms (UPDRS) and suggest an ongoing process of cortical reor- ganization with functional consequences . Dopamine has been implicated in the modulation of neuroplasticity , and the loss of dopaminergic neurons in PD may have secondary effects on cortical organization or limit the natural ability of plasticity mechanisms to compen- sate for disease-related processes, and there is some indi- cation that NBS may be more effective when applied during levodopa therapy, when plasticity mechanisms may be more functional [26,27]. As well, cortical rTMS interventions can lead to release of dopamine in the basal ganglia and raise serum dopamine levels . As to whether NBS can have a lasting benefit in a progressive disease such as PD, in which the primary pathology is sub- cortical, and which manifests as a generalized disorder, is uncertain. However a number of NBS interventions have been trialed in PD and have yielded some modest if tran- sient functional improvement, and meta-analysis of rand- omized controlled trials in PD indicate NBS can be beneficial over and above placebo effects . Plasticity in PD may be functional in the earlier stages of the dis- ease, as the brain adapts to the initial loss of dopaminergic neurons, but is probably dysfunctional later in the pro- gression of the disease as plasticity mechanisms become gradually impaired as a result of dopamine depletion. Dystonia
studies have demonstrated that cognitive de ﬁ cits are present across a broad range of cognitive domains in depression, executive function de ﬁ cits associated with frontal lobe dys- function are also reported to be prominent among depressed patients. 3 Depression leads to a series of molecular and cellular events which include changes in intracellular signal- ing, gene expression, neuronal function, and cellular archi- tecture within brain regions that control mood and cognition. 1 Affected brain regions include the amygdala, prefrontal cortex, hippocampus, thalamus, cingulate cortex, insula, and superior temporal gyrus. 1 Individuals with depression tend to translate a negative bias in perception, attention, and memory into conscious thoughts, memories, and actions, often showing greater attention and memory to negative stimuli. 1 Indeed, these emotion-laden functions related to negative affect are sometimes referred to as “ hot ” cognition, to distinguish them from “ cold ” cognition, or emotion-independent areas including executive function, information processing speed, learning and memory, and attention/concentration. 1 One STAR*D study report found that the patients who had not regained normal functioning at remission had a higher depression relapse compared with patients who had recovered normal functioning. 1,4 Repetitive transcranial magnetic stimulation (rTMS) is a noninvasivebrainstimulation technique that is considered a valuable and promising technique for improving cognitive symptoms in treatment-resistant depression (TRD) 5,6 and traumatic brain injury 7 Hayasaka et al reported that 10 daily sessions of 20-Hz left prefrontal rTMS in patients with major depression increased the hippocampal volume on the stimulated side, which could potentially be related to the improvement of cognitive function. 8 Nilakantan et al ’ s study demonstrated that high-frequency transcranial magnetic stimulation selectively modi ﬁ ed neural and beha- vioral hallmarks of age-related memory impairment, indicat- ing effective engagement of memory intervention targets in older adults. 9 Shinba et al. ’ s study demonstrated increase of frontal cerebral blood volume during TMS in depression is related to treatment effectiveness using near-infrared spectroscopy. 10
Noninvasivebrainstimulation methods, including repetitive transcranial magnetic stimulation and transcranial direct current stimulation (tDCS), have received considerable attention in recent years for use in the study and treatment of neurological conditions. Of these methods, tDCS is considered particularly promising due to its ease of use and ability to confer polarity-dependent effects on brain excitability, making it an excellent option for clinical treatment of neurological and psychiatric diseases. While generally regarded as safe when following standard protocols, the effects of tDCS on cerebral blood vessels and blood-brain barrier (BBB) functions remain poorly understood. Here, we provide an overview of tDCS in the context of BBB function, summarize the current literature, and discuss implications for future research. To date, no alterations or damage to the BBB have been reported after weak tDCS stimulations in human subjects; however, some animal studies have reported alterations to BBB function following increased tDCS intensity, with inconsistencies in the effective tDCS polarity used to produce these BBB disruptions between studies. Further research will be necessary to evaluate the effects of tDCS on the BBB under various conditions. Finally, we discuss the potential of tDCS for enhancing drug delivery to the central nervous system, which may become possible as we refine our understanding of the effects of tDCS on BBB permeability.
Transcranial direct current stimulation (tDCS) – one of the noninvasivebrainstimulation (NIBS) methods – can increase or decrease the cortical excitability accord- ing to polarity (anodal vs. cathodal) and be used to modulate the synaptic plasticity to promote long-term functional recovery via long-term depression or potenti- ation [12, 13]. Recent clinical trials evaluating patients with stroke have reported the potential benefits of tDCS for motor recovery . Neuroplastic changes after TBI and results from animal studies also suggest that tDCS could improve the motor deficit in TBI, although clinical trials using tDCS for motor recovery in TBI are cur- rently lacking .
neurological symptoms were identified and excluded from the study via the Neurological Symptom Checklist found in Appendix E. One participant was excluded from the study secondary to general anxiety of the protocol and reoccurring migraine headaches. Participants that satisfied all inclusion / exclusion criteria were assigned a number between 1-10. Each number was written on a slip of paper and then placed in a bowl. Slips of paper were selected out of the bowl one at a time. Odd number selections were assigned to the TMS stimulation group, and even number slips were assigned to the tDCS stimulation group. Each participant was issued a detailed schedule corresponding with 8 appointment times. The goal of the 1 st appointment was to screen patients and provide information about the study. During appointment 2, participants underwent cortical mapping, and the region corresponding with the first dorsal interosseous (FDI) muscle of the nondominant M1 was identified. In addition, baseline cortical excitability of the hand region of motor cortex was measured and participants completed familiarization training of all assessment. Appointment 3 was the first official day of training. On this day, participants completed baseline testing followed by the first 9-minute training session in accordance with their assigned group. Appointments 4 and 5 took place 24 and 48 hours after appointment 3, respectively, and consisted of the same cortical stimulation and 9 minute training session. During appointment 6, participants completed the final 9 minute training session followed by post-training testing. In addition, cortical excitability of the hand region of the motor cortex was again measured. Appointments 7 and 8 occurred 24 hours and 7 days after the last day of training, respectively, and primarily included post- training testing. See Figure F.1 for a graphical representation of the study layout.
cine, excessive or suppressed emotions affect the normal circulation of Chi in the body. Stimulating acupoints in the body generates and smoothens the flow of Chi (10). In the past few years, com- plementary therapies such as acupressure, acu- puncture, and transcutaneous electrical acupoint stimulation are effective for managing depression or anxiety symptoms (11). Acupuncture might be superior to antidepressants in improving clinical response and reducing depressive symptoms of PSD patients (12). Transcutaneous electrical acu- point stimulation improved depressive mood sta- tus among elders in a nursing home (7). No study has specifically applied electrical acupuncture stimulation to treat anxious mood status of pa- tients with lung cancer during palliative care. There is a paucity of information with regard to the effectiveness of management of symptoms indicating anxiety in palliative care of patient. The present study was aimed to assess the influ- ence of electrical acupuncture stimulation on self- reported anxiety in palliative care among patients with lung cancer.
In the normally functioning HPAA, the hypothalamus secretes corticotropin- releasing hormone (CRH), which stimulates the anterior pituitary to secrete ACTH. ACTH in turn stimulates adrenal cortical secretion of cortisol. Hypothalamic secretion of arginine vasopressin (AVP) also stimulates anterior pituitary secretion of ACTH. By a negative feedback loop, cortisol inhibits pituitary secretion of ACTH and hypotha- lamic secretion of CRH. In the case of an ACTH-secreting pituitary adenoma, ACTH is secreted without hormonal stimulation. Therefore, despite negative feedback loops triggered by excess cortisol, ACTH is autonomously secreted, further increasing cortisol levels, leading to Cushingoid signs and symptoms.
These simplifications could potentially cause under- estimation of the field generated by the electrode, and introduce potential certain inaccuracy in the modeling. Some investigators have acknowledged this problem in previous studies. Among them, Kotnik  suggested that the placement of a biological cell into an electric field leads to a local distortion of the cell in its vicinity, while Lee and Grill  further advised that this distor- tion is maximal when the electrode is in close proximity to the neuron. A recent numerical study  suggested that decreases in tissue conductivity could result in a de- crease in the volume of neuronal tissue activated by an electrode during chronic implantation. Lastly, McIntyre et al.  considered potential errors introduced by the aforementioned assumptions in their simulations with NEURON while studying deep brainstimulation.
HIV dementia is a major cause of morbidity and a significant risk factor for death in persons with AIDS (13, 49). The brain may be subject to ongoing changes during the course of HIV infection (50–53). The difficulty in quantifying advancing infection in brain has compromised efforts to delineate mechanisms of HIV neuropathogenesis and to identify neuroprotec- tive agents (54). Findings from this investigation sup- port the use of diffusion tensor imaging for measuring diffuse brain changes in cases of HIV-associated cog- nitive impairment. Further studies are necessary to determine whether diffusion tensor imaging measures are sensitive to subclinical changes in asymptomatic patients with HIV. Diffusion tensor imaging mea- sures may have potential clinical use for identifying individuals at risk for progression and for monitoring clinical status. Longitudinal studies of region-specific diffusion tensor imaging parameters (eg, in caudate nucleus, putamen, and deep white matter) may pro- vide insights concerning early viral entry into brain, the relative resistance or sensitivity of specific brain regions to HIV-associated injury, and factors associ- ated with sudden change in status. Sequelae such as early cognitive decline in persons with HIV may per- sist, improve with anti-retroviral therapy, or progress to frank dementia. Noninvasive markers of status may be useful for evaluation of treatment failure, for in- forming efforts to modify therapy, and for determin- ing whether specific cognitive deficits are associated with changes in tissue or are more influenced by other factors (eg, depression). Diffusion tensor imaging in- dices may have potential clinical use for assessing therapeutic response to anti-retroviral therapy within CNS and for distinguishing reversible and irreversible HIV-induced injury. Region-specific increases in FA or changes in ADC may reflect treatment response; more pronounced or persistent diffusion tensor im- aging abnormalities may be consistent with worsening or irreversible changes to tissue.
With the effectiveness of non-invasive M1 stimulation recently demonstrated there has been a call from patients to facilitate more convenient forms of this therapy. It has been in direct response to this patient lead call that the present exploration of home-based non-invasive tDCS of M1 has been devised. Self-administration of tDCS obvi- ously has both advantages and disadvantages. While it may not confer the same accuracy and consistency as clinic-based, professionally administered stimulation ses- sions, it does reflect the necessity for patients to be able to administer this type of therapy in the convenience of their own home. It is recognised that there will be limitations on the ability to control timing of stimulus applications and there may be some variability in technique. However, all subjects will be thoroughly briefed in the correct posi- tioning of electrode placement and measurements will be made against previously taken MRI scans and navigated TMS data. These measurements are transferred on to securely locating headbands that are fitted individually to each patient. Each subject is observed while placing the electrodes on a number of occasions to ensure correct technique. The study described is very much a real-world test of both the effectiveness and practicality of using tDCS in this patient population, with a method of delivery that is based on other portable home-use devices such as transcutaneous electrical nerve stimulation, which has been in use for several years, albeit with varying success. If a positive effect is demonstrated it may represent an im- portant cost-efficient option for non-invasive motor cortex stimulation in the treatment of chronic pain.
To our knowledge, adequate localization and focusing of energy patterns and the cal- culation of the temperature distribution in a realistic 3D head model containing a deeply seated as well as a superficial brain tumor due to irradiation by a simple easy to fabricate antenna excited at a single frequency placed in a partial half ellipsoidal nonin- vasive air filled hyperthermia applicator is still lacking. In this study, we numerically designed a noninvasive hyperthermia applicator system composed of a patch antenna, a partial half ellipsoidal chamber and a head model containing a tumor. The FDTD method was used to compute both the SAR patterns and the temperature distribution in three different head models. Several improvement steps were performed on all of the applicator system configurations to adequately ensure sufficient and focused energy de- position and temperature distribution in the brain tumor. The system is capable of heating deep seated as well as superficial brain tumors by placing the center of the tumor at a pre-specified location (one of the foci) controlled by the operator of the pro- posed hyperthermia system. The use of a partial half ellipsoidal chamber ensures better head positioning and patients comfort compared to whole ellipsoidals.
Consequently, Lippold and Redfearn found many benefits of brain polarization to treat depressive disor- ders in patients, especially in those who had failed to respond to prior methods, including ECT (Electrocon- vulsive Therapy). This became more evident following the experiments on rats’ cortex in collaboration with Bindman(Bindman, et al., 1964; Lippold & Redfearn, 1964; Redfearn, Lippold, & Costain, 1964). Taken in to account that all subjects were healthy , these inves- tigators found that the anodal stimulation increases the alertness, mood and motor activity, while the cathodal one results in apathy and quietness(Lippold & Redfearn, 1964; Redfearn, et al., 1964). Costain continued to carry out some controlled experiments to further prove the efficacy of such a method(Costain, Redfearn, & Lip- pold, 1964). However, the desire to hold on the studies disappeared while trying to reach the analogous results (Arfai, Theano, Montagu, & Robin, 1970; Hall, Hicks,
because the patterns that result from neuroplasticity are often unknown, it has proven difficult to determine what these changes in self-perspectival organization might be. Another aspect of neurofeedback training is that it forces the subject to reflect on their own mental states with aid of the technology (direct feedback). According to Moran, these mental states are corrupted upon reflection, which, upon occurring unnaturally, can cause unnatural changes in the subject’s current mental state(s). Neurofeedback may also change self-related processing, during and after the procedure. During the procedure, subject may reflect on their thoughts differently based on the feedback they have received. After the procedure, changes may occur based on adjusted neural patterns that give rise to specific thinking patterns or a specific mental state. Self-specifying might be different due to the fact that subjects reflect on aspects of modified behavior. Both these processing can give rise to a different self-understanding, which can mean a subject forms different thoughts about him or herself, or what he or she is. The analysis of the effects of neurofeedback on a societal level brought to light two major possible effects. The first is that subjects and the general public increasingly feel like their brain is an autonomous system, due to the means of the forced direct reflective method and the general nature of the procedure, in addition to the estranging approach that the offering parties employ in relation to the brain. This can lead to a shift in perspective on human nature as well, which would raise questions in the areas of authenticity, responsibility, control and free will. The second is based on the fact that in neurofeedback, a mechanism is used that is comparable to the neural mechanisms involved in addiction. This raises several questions, amongst other things with regards to the ethical justification of the procedure and the possible consequences for authenticity of the subject.
Phosphorus magnetic resonance spectroscopy MRS) was originally o f particular interest in view of its ability to monitor energy metabolism, by detection of signals from ATP, phosphocreatine (PCr) and inorganic phosphate (Pi). Studies initially concentrated on muscle, but later it was evident that useful cerebral changes could be seen in hypoxic ischaemic encephalopathy in neonates (Cady et a l, 1983; Hope et a l, 1984; Younkin et a l , 1994). A fall in energy status can be demonstrated in the brain of affected infants, seen predominantly as a fall in the PCr/Pi ratio. This has been correlated with neuro- developmental outcome (Roth et a l, 1992). ^*P MRS studies have also been performed in a small number of adults with temporal (Hugg et a l, 1992; Kuzniecky et a l, 1992) and frontal lobe (Garcia et a l, 1994; Laxer et a l, 1992) epilepsy, but results have been inconsistent. An increased inorganic phosphate has been demonstrated on the side of the seizure focus in TLE (Hugg et a l, 1992; Kuzniecky et a l, 1992), but no such change has been found in frontal lobe epilepsy (Garcia et a l, 1994). Furthermore, one group has demonstrated an increase in pH and decreased phosphomonoester ipsilateral to the seizure focus in temporal and frontal lobe epilepsy (Garcia et a l, 1994; Hugg et a l, 1992) but this was not confirmed in TLE by a second group (Kuzniecky et a l, 1992).
To avoid these complications “Non –invasive Deep BrainStimulation via Temporally Interfering Electrical Fields “which describes a non –surgical technique that achieves an effect similar to that of invasive DBS. In which the electrodes are placed on the scalp, by taking advantage of a phenomenon known as temporal interface. This strategy requires generating two high-frequency electrical currents using electrodes placed outside the brain. These fields are too fast to drive neurons. However, these currents interfere with one another in such a way that where they intersect, deep in the brain, small region of low-frequency current is generated inside neurons, this low-frequency current can be used to drive neurons electrical activity, while the high-frequency current passes through surrounding tissues with no effect. Non-invasive DBS can be used for patients with PD of at least 4 years duration and 4 month of motor complications and can improve tremor, rigidity, slowness.