Network connectivity and individual responses to brain stimulation in the human motor system.

The mechanisms driving cortical plasticity in response to brain stimulation are still incompletely understood. We here explored whether neural activity and connectivity in the motor system relate to the magnitude of cortical plasticity induced by repetitive transcranial magnetic stimulation (rTMS). Twelve right-handed volunteers underwent functional magnetic resonance imaging during rest and while performing a simple hand motor task. Resting-state functional connectivity, task-induced activation, and task-related effective connectivity were assessed for a network of key motor areas. We then investigated the effects of intermittent theta-burst stimulation (iTBS) on motor-evoked potentials (MEP) for up to 25 min after stimulation over left primary motor cortex (M1) or parieto-occipital vertex (for control). ITBS-induced increases in MEP amplitudes correlated negatively with movement-related fMRI activity in left M1. Control iTBS had no effect on M1 excitability. Subjects with better response to M1-iTBS featured stronger preinterventional effective connectivity between left premotor areas and left M1. In contrast, resting-state connectivity did not predict iTBS aftereffects. Plasticity-related changes in M1 following brain stimulation seem to depend not only on local factors but also on interconnected brain regions. Predominantly activity-dependent properties of the cortical motor system are indicative of excitability changes following induction of cortical plasticity with rTMS.

Exploring the after-effects of theta burst magnetic stimulation on the human motor cortex: a functional imaging study.

Theta burst stimulation (TBS) is a protocol of subthreshold repetitive transcranial magnetic stimulation (rTMS) inducing changes in cortical excitability. From functional imaging studies with conventional subthreshold rTMS protocols, it remains unclear what type of modulation occurs (direction and dependency to neural activity) and whether putative effects are bound to unspecific changes in cerebral perfusion or require a functional challenge. In a within-subjects (n = 17) repeated measurement design including real TBS and a control session without stimulation, we examined neural activation in a choice-reaction task after application of intermittent TBS, a protocol, which enhances cortical excitability over the left motor cortex (M1). Brain activity was monitored by blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging interleaved with measuring regional cerebral blood flow (rCBF) at rest using MR-based perfusion imaging. On a separate day, TMS-induced compound muscle action potentials (cMAPs) amplitude of the right hand was measured after excitatory TBS. Compared to control, a significant decrease in BOLD signal due to right hand motor activity during the choice-reaction task was observed mainly in the stimulated M1 and motor-related remote areas after stimulation. This decrease might represent a facilitating effect, because cMAPs amplitude increased upon TBS compared to control. No changes in rCBF at rest were observed. The data demonstrate that subthreshold intermittent TBS targets both the stimulated cortical area as well as remote areas. The facilitation changing the efficacy of neural signal transmission seems to be reflected by a BOLD signal decrease, whereas the network at rest does not appear to be affected.

Exploring the affective component of pain perception during aversive stimulation in borderline personality disorder.

In a pilot study, affective components of pain were assessed using repetitive peripheral magnetic stimulation (rPMS) in patients with borderline personality disorder and healthy controls. Significant differences in pain thresholds and in affective components of pain between both groups were found. rPMS was well tolerated and suitable for assessing pain.

Non-invasive electrical brain stimulation for vision restoration after stroke: An exploratory randomized trial (REVIS).

BACKGROUND: Occipital strokes often cause permanent homonymous hemianopia leading to significant disability. In previous studies, non-invasive electrical brain stimulation (NIBS) has improved vision after optic nerve damage and in combination with training after stroke. OBJECTIVE: We explored different NIBS modalities for rehabilitation of hemianopia after chronic stroke. METHODS: In a randomized, double-blinded, sham-controlled, three-armed trial, altogether 56 patients with homonymous hemianopia were recruited. The three experiments were: i) repetitive transorbital alternating current stimulation (rtACS, n = 8) vs. rtACS with prior cathodal transcranial direct current stimulation over the intact visual cortex (tDCS/rtACS, n = 8) vs. sham (n = 8); ii) rtACS (n = 9) vs. sham (n = 9); and iii) tDCS of the visual cortex (n = 7) vs. sham (n = 7). Visual functions were evaluated before and after the intervention, and after eight weeks follow-up. The primary outcome was change in visual field assessed by high-resolution and standard perimetries. The individual modalities were compared within each experimental arm. RESULTS: Primary outcomes in Experiments 1 and 2 were negative. Only significant between-group change was observed in Experiment 3, where tDCS increased visual field of the contralesional eye compared to sham. tDCS/rtACS improved dynamic vision, reading, and visual field of the contralesional eye, but was not superior to other groups. rtACS alone increased foveal sensitivity, but was otherwise ineffective. All trial-related procedures were tolerated well. CONCLUSIONS: This exploratory trial showed safety but no main effect of NIBS on vision restoration after stroke. However, tDCS and combined tDCS/rtACS induced improvements in visually guided performance that need to be confirmed in larger-sample trials.NCT01418820 (clinicaltrials.gov).

Mechanisms and applications of theta-burst rTMS on the human motor cortex.

Theta-burst Stimulation (TBS) is a novel form of repetitive transcranial magnetic stimulation (rTMS). Applied over the primary motor cortex it has been successfully used to induce changes in cortical excitability. The advantage of this stimulation paradigm is that it is able to induce strong and long lasting effects using a lower stimulation intensity and a shorter time of stimulation compared to conventional rTMS protocols. Since its first description, TBS has been used in both basic and clinical research in the last years and more recently it has been expanded to other domains than the motor system. Its capacity to induce synaptic plasticity could lead to therapeutic implications for neuropsychiatric disorders. The neurobiological mechanisms of TBS are not fully understood at present; they may involve long-term potentiation (LTP)- and depression (LTD)-like processes, as well as inhibitory mechanisms modulated by GABAergic activity. This article highlights current hypotheses regarding the mechanisms of action of TBS and some central factors which may influence cortical responses to TBS. Furthermore, previous and ongoing research performed in the field of TBS on the motor cortex is summarized.

Aggressive and Disruptive Behavior Among Psychiatric Patients With Major Depressive Disorder, Schizophrenia, or Alcohol Dependency and the Effect of Depression and Self-Esteem on Aggression.

Aggressive and disruptive behavior in inpatient settings poses a serious challenge for clinical staff and fellow patients. Hence, the aim of this study was to identify different aspects of aggressive and disruptive behavior in the context of an aberrant self-esteem or clinically manifested depression as potentially influencing factors. We collected self-reported data from 282 psychiatric patients [ICD-10 diagnoses for alcohol dependency, schizophrenia or major depressive disorder (MDD)] and compared it to healthy norm groups. As expected, all three patient groups scored higher in the aggression questionnaires than the norm group. Specifically, patients with MDD exhibited significantly higher externally directed aggression, reactive aggression, and irritability compared to controls. Patients with schizophrenia displayed higher irritability, while all three groups showed distinctly higher self-aggressiveness than healthy persons. We found a lower inhibition of aggression in alcohol dependent subjects compared to both the patient groups and the norm sample. Yet, the higher the self-esteem among alcohol dependent and MDD patients, the lower were their aggression scores; similarly, a lower self-esteem among patients diagnosed with schizophrenia resulted in heighten self-aggressiveness. Thus, our data suggests that therapeutic interventions for strengthening self-esteem in patients with a diagnosis of MDD, alcohol dependency or schizophrenia could reduce certain aspects of aggressive behavior. Therefore, it seems conceivable that strengthening self-esteem in psychiatric patients could contribute to the prevention of violence in clinical practice.

Analysis of background EEG activity in patients with juvenile myoclonic epilepsy.

PURPOSE: To analyze background EEG activity of patients with juvenile myoclonic epilepsy (JME) with and without antiepileptic drugs. METHODS: We studied the background EEG activity in 18 patients with JME. The qEEG analysis included absolute power (AP), relative power (RP) and mean frequency (MF) of delta, theta, alpha and beta bands. The Z scores were calculated by comparison with population parameters based on the age-dependent regression function. Seven patients were unmedicated (UM) and eleven medicated (M). RESULTS: The UM group presented 69 (4.32%) abnormal Z scores and 227 (9.05%) in the M group (P<0.001). In the UM group, AP delta abnormal Z scores were identified in frontotemporal and occipital leads. In AP alpha and beta bands an increase in Z scores was encountered in frontoparietal leads in three patients. In addition, in three patients, the AP theta Z scores were below -1.96 and distributed in all regions. In the M group, AP beta Z scores were above 1.96 in frontoparietal leads in 7 of 11 patients. The AP delta increased above 1.96 in frontotemporal and occipital leads in 6 patients of 11. The AP alpha showed an abnormal decrease in Z scores in 5 of 11 patients, whereas other 5 patients presented normal scores. The AP theta presented 7 normal Z scores out of 11; this band exhibited the lowest number of abnormalities of the 4. CONCLUSION: Patients with JME have an increase in AP delta, alpha and beta bands, which is more evident in frontoparietal regions.

Repetitive transcranial magnetic stimulation decreases the number of seizures in patients with focal neocortical epilepsy.

PURPOSE: To evaluate the number of seizures and interictal epileptiform discharges (IEDs) in patients with focal neocortical epilepsy before, during and after rTMS. METHODS: Twelve patients (seven men and five women, mean age 29.3+/-15.8 years) were studied. An open-label study with baseline (4 weeks), intervention (2 weeks) and follow-up (8 weeks) periods was carried out. Repetitive transcranial magnetic stimulation (rTMS) with 900 pulses, intensity of 120% motor resting threshold and 0.5Hz frequency was used. A 120 channel EEG was recorded; an electrical source analysis of IEDs with Variable Resolution Electromagnetic Tomography (VARETA) was performed. The number of seizures per week and IEDs per minute were measured and compared in the three periods. RESULTS: During the basal period the mean seizure frequency was 2.25 per week; in the intervention period it decreased to 0.66 per week (F=2.825; p=0.0036) which corresponds to a 71% reduction. In the follow-up period the mean frequency was 1.14 seizures per week, that is, a 50% reduction in the number of seizures. In the visual EEG analysis, the baseline IED frequency was 11.9+/-8.3events/min; it decreased to 9.3+/-7.9 during 2 weeks of rTMS with a further reduction to 8.2+/-6.6 in the follow-up period. These differences however were not significant (p=0.190). CONCLUSION: We conclude that 2 weeks of rTMS at 0.5Hz with a figure-of-eight coil placed over the epileptic focus, determined with VARETA, decreases the number of seizures in patients with focal epilepsy, without reduction in IEDs.

Vision Restoration in Glaucoma by Activating Residual Vision with a Holistic, Clinical Approach: A Review.

How to cite this article: Sabel BA, Cárdenas-Morales L, Gao Y. Vision Restoration in Glaucoma by activating Residual Vision with a Holistic, Clinical Approach: A Review. J Curr Glaucoma Pract 2018;12(1):1-9.

Mental stress as consequence and cause of vision loss: the dawn of psychosomatic ophthalmology for preventive and personalized medicine.

The loss of vision after damage to the retina, optic nerve, or brain has often grave consequences in everyday life such as problems with recognizing faces, reading, or mobility. Because vision loss is considered to be irreversible and often progressive, patients experience continuous mental stress due to worries, anxiety, or fear with secondary consequences such as depression and social isolation. While prolonged mental stress is clearly a consequence of vision loss, it may also aggravate the situation. In fact, continuous stress and elevated cortisol levels negatively impact the eye and brain due to autonomous nervous system (sympathetic) imbalance and vascular dysregulation; hence stress may also be one of the major causes of visual system diseases such as glaucoma and optic neuropathy. Although stress is a known risk factor, its causal role in the development or progression of certain visual system disorders is not widely appreciated. This review of the literature discusses the relationship of stress and ophthalmological diseases. We conclude that stress is both consequence and cause of vision loss. This creates a vicious cycle of a downward spiral, in which initial vision loss creates stress which further accelerates vision loss, creating even more stress and so forth. This new psychosomatic perspective has several implications for clinical practice. Firstly, stress reduction and relaxation techniques (e.g., meditation, autogenic training, stress management training, and psychotherapy to learn to cope) should be recommended not only as complementary to traditional treatments of vision loss but possibly as preventive means to reduce progression of vision loss. Secondly, doctors should try their best to inculcate positivity and optimism in their patients while giving them the information the patients are entitled to, especially regarding the important value of stress reduction. In this way, the vicious cycle could be interrupted. More clinical studies are now needed to confirm the causal role of stress in different low vision diseases to evaluate the efficacy of different anti-stress therapies for preventing progression and improving vision recovery and restoration in randomized trials as a foundation of psychosomatic ophthalmology.

Effects of two different cycles of vagus nerve stimulation on interictal epileptiform discharges.

PURPOSE: To evaluate the effects of two cycles of vagus nerve stimulation (VNS), 30 s/5 min and 7 s/18 s on the interictal epileptiform discharges (IEDs). METHODS: Twenty patients were studied, 12 with generalized and 8 with partial seizures. An EEG of 120 channels was performed during 3 different conditions, each one lasting 30 min: basal state (BS), 30 s/5 min and 7 s/18 s VNS cycles. The number and duration of IEDs, time of IEDs in 1 min (TIEDM), IEDs/NIEDs index and the spike-free period (SFP) were determined. RESULTS: In 16 patients (80%), IED decreased during 30 s/5 min cycle (Group 1) and increased in 4 (Group 2). In Group 1, during the 30 s/5 min cycle the following variables showed a decrease: TIEDM, from 12.64 s to 9.62 s (p=0.001); IED/NIED index, from 0.53 to 0.31 (p=0.021), and IED duration, from 1.57 s to 1.05 s (p=0.015); whereas SFP duration increased from 20.06 s to 37.73 s (p=0.008). The decrease in IED was 41% and the increase in SFP 88%. In the 7s/18s cycle, only SFP had an increase, 72% (p<0.043). In Group 2, an increase in IED during both cycles was found. In the 30 s/5 min cycle, TIEDM increased 56% (p=0.042) and IED/NIED index 259% (p=0.040). CONCLUSION: VNS modifies IED in an acute form, in 80% of patients the 30 s/5 min cycle decreases the epileptiform activity and it is not modified by 7 s/18 s cycle. In 20% of patients, both cycles increase the epileptiform activity.

Neural activation in humans during a simple motor task differs between BDNF polymorphisms.

The BDNF Val66Met polymorphism has been linked to decreased synaptic plasticity involved in motor learning tasks. We investigated whether individual differences in this polymorphism may promote differences in neural activity during a two-alternative forced-choice motor performance. In two separate sessions, the BOLD signal from 22 right-handed healthy men was measured during button presses with the left and right index finger upon visual presentation of an arrow. 11 men were Val66Val carriers (ValVal group), the other 11 men carried either the Val66Met or the Met66Met polymorphism (Non-ValVal group). Reaction times, resting and active motor thresholds did not differ between ValVal and Non-ValVal groups. Compared to the ValVal group the Non-ValVal group showed significantly higher BOLD signals in the right SMA and motor cingulate cortex during motor performance. This difference was highly consistent for both hands and across all four sessions. Our finding suggests that this BDNF polymorphism may not only influence complex performance during motor learning but is already associated with activation differences during rather simple motor tasks. The higher BOLD signal observed in Non-ValVal subjects suggests the presence of cumulative effects of the polymorphism on the motor system, and may reflect compensatory functional activation mediating equal behavioral performance between groups.

Is rTMS an effective therapeutic strategy that can be used to treat Parkinson's disease?

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Parkinson's disease (PD) is a neurodegenerative process characterized by numerous motor and nonmotor clinical manifestations for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A possible method of rehabilitation that may be effective and potentially viable for use in clinical practice is rTMS. Here, we focus on the basic foundation of rTMS, the main findings of rTMS from animal models, the effects of rTMS on sensorimotor integration in patients with PD, and the experimental advances of rTMS that may become a viable clinical application to treat the disease.

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial.

Selecting a suitable sham condition within the frame of repetitive transcranial magnetic stimulation (rTMS) treatment trials is a central issue. On the one hand, the ideal sham condition should not have a real stimulation effect; on the other hand, it should not be recognized as sham by patients, particularly when considering that real stimulation conditions come along with rTMS specific side effects. Within the course of a multi-centre trial assessing the antidepressant effects of rTMS, patients were randomized to sham or real stimulation, in both cases using a standard stimulation coil. In one centre, patients (n=33) were asked about their impression whether they received the sham or the real treatment, and if they would recommend the treatment to others. 29 patients returned the questionnaires and were included into the analysis. From 15 subjects with real stimulation, 11 suggested to have obtained real, and 4 to have obtained sham. From 14 sham stimulated subjects, 9 suggested to have obtained the real condition and 5 to have been sham stimulated. This difference was not significant (p=0.60, chi square test). In addition, the major part of patients in both stimulation conditions would recommend rTMS to others. In both conditions, real and sham, the majority of subjects believed to have obtained the real condition. This implies suitability of the sham condition used since subjects appeared not to be able to identify the condition. The results imply the feasibility of a valid sham condition with a "real" coil.