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Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca2+ concentration alterations.

Introduction Motor evoked potentials (MEP) in response to anteroposterior transcranial (AP) magnetic stimulation (TMS) are sensitive to the TMS pulse shape. We are now able to isolate distinct pulse properties, such as pulse width and directionality and evaluate them individually. Different pulse shapes induce different effects, likely by stimulating different populations of neurons. This implies that not all neurons respond in the same manner to stimulation, possibly, because individual segments of neurons differ in their membrane properties. Objectives To investigate the effect of different pulse widths and directionalities of TMS on MEP latencies, motor thresholds and plastic aftereffects of rTMS. Methods Using a controllable pulse stimulator TMS (cTMS), we stimulated fifteen subjects with quasi-unidirectional TMS pulses of different pulse durations (40 μs, 80 μs and 120 μs) and determined thresholds and MEP AP latencies. We then compared the effects of 80 μs quasi-unidirectional pulses to those of 80 μs pulses with different pulse directionality characteristics (0.6 and 1.0 M ratios). We applied 900 pulses of the selected pulse shapes at 1 Hz. Results The aftereffects of 1 Hz rTMS depended on pulse shape and duration. 40 and 80 μs wide unidirectional pulses induced inhibition, 120 μs wide pulses caused excitation. Bidirectional pulses induced inhibition during the stimulation but had facilitatory aftereffects. Narrower pulse shapes caused longer latencies and higher resting motor thresholds (RMT) as compared to wider pulse shapes. Conclusions We can tune the aftereffects of rTMS by manipulating pulse width and directionality; this may be due to the different membrane properties of the various neuronal segments such as dendrites. Significance To date, rTMS frequency has been the main determinant of the plastic aftereffects. However, we showed that pulse width also plays a major role, probably by recruiting novel neuronal targets.

Objective: To spot the frontal theta/beta ratio alterations during Tests of Variance of Attention (TOVA) in Egyptian attention deficit hyperactivity disorder (ADHD) children. Methods: This is a cross sectional study performed in Clinical Neurophysiology Unit, Cairo University, Egypt. It included 2 groups, each of 52 children (one of them with ADHD and the other were normal control). EEG was recorded for every subject during normal relaxing circumstance with eyes opened as well as during TOVA. Results: Comparing both groups revealed statistically significant difference in the theta/beta ratio in both state (normal relaxing with eyes opened and during TOVA), also we found that the theta/beta ratio decreased in normal group (during concentration) while in the ADHD group it increased with a specific pattern. Conclusion: The theta/beta ratio can be of value in helping for differential diagnosis in patients presenting with mild ADHD.

IntroductionHigh frequency repetitive transcranial magnetic stimulation induces excitation when applied to the motor cortex as reflected by the increase MEP amplitudes after the stimulation. The effects differ according to pulse width, probably due to higher content of energy in the wider pulses and their ability to cause wider activation in comparison to shorter pulse shapes. Here we focus on the aftereffects generated with high frequency controllable pulse TMS (cTMS) with different pulse widths.ObjectivesTo investigate the influence of pulse energy by using different stimulation intensities and pulse widths on the excitatory plastic aftereffects of high frequency (HF) rTMS.MethodsUsing a controllable pulse stimulator TMS (cTMS), we stimulated the hand motor cortex with 5 Hz rTMS applying 1200 bidirectional pulses with the main component widths of 80, 100 and 120 microseconds. 14 healthy subjects were initially investigated for six randomized sessions first with 80% RMT for anterior-posterior (AP) and posterior-anterior (PA). Then three more sessions using same pulse widths were added for 90% RMT anterior-posterior (AP).Results80% HF rTMS did not produce any significant excitation in either AP or PA direction. 90% RMT AP stimulation with 100 and 120 microsecond-wide pulses were more excitatory, when compared to the 80 microsecond-wide pulses. We also found a correlation between the individual pulse energy and the plastic outcome of each session.ConclusionsHF rTMS with wider pulses is more effective in producing excitatory aftereffects, an effect that correlated with the higher energy content of wider pulses and higher intensity.SignificanceThe findings here suggest that wider pulses are capable of inducing more excitation, a fact that could contribute to better results in future clinical studies performed with wider pulses.

Patients with functional pain disorders often complain of generalized sensory hypersensitivity, finding sounds, smells, or even everyday light aversive. The neural basis for this aversion is unknown, but it cannot be attributed to a general increase in cortical sensory processing. Here, we quantified the threshold for aversion to light in patients with fibromyalgia, a pain disorder thought to reflect dysregulation of pain-modulating systems in the brain. These individuals expressed discomfort at light levels substantially lower than that of healthy control subjects. Complementary studies in lightly anesthetized rat demonstrated that a subset of identified pain-modulating neurons in the rostral ventromedial medulla unexpectedly responds to light. Approximately half of the pain-facilitating "ON-cells" and pain-inhibiting "OFF-cells" sampled exhibited a change in firing with light exposure, shifting the system to a pronociceptive state with the activation of ON-cells and suppression of OFF-cell firing. The change in neuronal firing did not require a trigeminal or posterior thalamic relay, but it was blocked by the inactivation of the olivary pretectal nucleus. Light exposure also resulted in a measurable but modest decrease in the threshold for heat-evoked paw withdrawal, as would be expected with engagement of this pain-modulating circuitry. These data demonstrate integration of information about light intensity with somatic input at the level of single pain-modulating neurons in the brain stem of the rat under basal conditions. Taken together, our findings in rodents and humans provide a novel mechanism for abnormal photosensitivity and suggest that light has the potential to engage pain-modulating systems such that normally innocuous inputs are perceived as aversive or even painful.

Cannabis has been used in medicine for centuries. Modern understanding of the clinical effects of cannabis and cannabinoids in the treatment of pain is evolving. Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics. The two main phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The endocannabinoid system is comprised of endogenous cannabinoids and cannabinoid receptors including CB1 receptors located primarily in the brain and peripheral tissue and CB2 receptors in the immune and hematopoetic systems. Cannabis bioavailability and metabolism varies significantly for inhaled versus oral/sublingual routes of delivery. Large, well-designed clinical trials are limited; however the studies available provide evidence to support the use of cannabinoids for some cancer, neuropathic, and chronic pain conditions.

Introduction Repetitive transcranial magnetic stimulation (rTMS) has been found to be a promising noninvasive therapeutic tool for a variety of neuropsychiatric conditions. Therapeutic utility of rTMS was classified to have class A evidence for treatment of depression and chronic pain. In different stimulation protocols intervals have been introduced between high frequency (HF) trains for safety concerns and other practical reasons, which might affect efficacy of rTMS therapy. Objectives To examine effects of temporal patterns of rTMS beyond stimulation frequency in its classical sense on efficacy of rTMS. In-vitro neuronal cultures were used to compare between protocols used by Herwig et al. (2007) (Protocol A) and O’Reardon et al. (Protocol B). Both used 10 Hz but with different parameters such as inter-train interval (ITI) and average stimulation frequency per minute resulting in different outcome. Methodology To test the hypothesis that intervals between rTMS trains can affect their therapeutic efficacy, we extracted the data from 57 papers on clinical trials about depression and chronic pain discussed in Lefaucheur et al. (2014). The inter-train interval (ItI) and average frequency, defined as a ratio of total pulse number to the entire duration of a single rTMS session, were plotted against the percentage improvement of the outcome scale, which was the Hamilton Depression Scale for depression and Visual analog scale for the chronic pain. To augment the analysis, in vitro experiments were conducted on cultured cortical neurons that were functionally isolated from their network using a cocktail of synaptic blockers. 10 Hz Trains were applied with ITI of 8 s: protocol (A) and 26 s: protocol (B). Results HFrTMS protocols using ITI 20 s were less effective in comparison to longer ITI in depression and pain as well as accordingly average frequencies 1.3 Hz showing better results. The in vitro experiments comparing protocol (A) lead to a substantial fraction of response failures, while in protocol (B) practically no response failures occur. This difference is attributed to the longer ITI, 26 s, in protocol (B). Discussion Saturation of neuronal firing by HFrTMS without allowing some time for recovery may lead to neuronal response failures (NRFs) compromising the efficacy of higher frequency stimulation. Longer ITIs would allow the neurons to recover from the NRF. Significance The efficacy of rTMS stimulation protocols may be impaired under too high average stimulation frequency because of conduction failures.

Results of previous studies suggest that β-adrenoreceptor activation may augment pain, and that β-adrenoreceptor antagonists may be effective in reducing pain, particularly in individuals not homozygous for the catechol-O-methyltransferase (COMT) high-activity haplotype.Consenting patients admitted for thermal burn injury at participating burn centers were genotyped; those who were not high-activity COMT homozygotes were randomized to propranolol 240 mg/d or placebo. Primary outcomes were study feasibility (consent rate, protocol completion rate) and pain scores on study days 5 to 19. Secondary outcomes assessed pain and posttraumatic stress disorder symptoms 6 weeks postinjury.Seventy-seven percent (61/79) of eligible patients were consented and genotyped, and 77% (47/61) were genotype eligible and randomized. Ninety-one percent (43/47) tolerated study drug and completed primary outcome assessments. In intention-to-treat and per-protocol analyses, patients randomized to propranolol had worse pain scores on study days 5 to 19.Genotype-specific pain medication interventions are feasible in hospitalized burn patients. Propranolol is unlikely to be a useful analgesic during the first few weeks after burn injury.

The recent emergence of better rTMS stimulators allows the generation of various pulse sequences and patterns and the following question arise - how to optimize the efficiency of rTMS scheduling in clinical trials? While the existing literature reports seemingly contradicting results, the phase-space for such an exhaustive optimization search is large and includes many dimensions such as repetition frequency, pulse intensity, pulse duration, number of pulses, pulse shape and intervals between repeated treatments. We try to identify the relevant guidelines and trends to optimize the efficiency of rTMS scheduling. The underlying physical mechanism is the network conductance which is significantly affected by neuronal plasticity in the form of neuronal response failures (NRFs).

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of Amlexanox (AMX) in its bioadhesive buccal tablets. The proposed method is based on measuring the native fluorescence of the methanolic solution of AMX at 400 nm after excitation at 242 nm in 0.2 M borate buffer (pH 10) and 0.5% w/v sodium dodecyl sulfate (SDS) solution. The interaction of AMX with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of AMX. The relative fluorescence intensity-concentration plot was rectilinear over the range 5.0-80.0 ng/mL, with a lower detection limit of 0.57 ng/mL and a lower quantification limit of 1.74 ng/mL. The proposed method was successfully applied to the analysis of AMX in its commercial tablets. Moreover, content uniformity testing was conducted by applying official USP guidelines. Statistical evaluation and comparison of the data obtained using the proposed and comparison methods revealed good accuracy and precision for the proposed method.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of amisulpride (AMS) and bumidazone (BUM) in tablet form. The proposed method is based on measuring the native fluorescence of the studied drugs in methanol at 360 and 344 nm after excitation at 276 and 232 nm for AMS and BUM, respectively. The fluorescence-concentration plots were rectilinear over the ranges of 5.0-60.0 ng/mL for AMS and 0.5-5.0 µg/mL for BUM. The lower detection limits were 0.70 ng/mL and 0.06 µg/mL, and the lower quantification limits were 2.0 ng/mL and 0.18 µg/mL for AMS and BUM, respectively. The method was successfully applied for the analysis of AMS and BUM in commercial tablets. Statistical evaluation and comparison of the data obtained using the proposed and comparison methods revealed good accuracy and precision for the proposed method.

The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in "off" state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p = 0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p = 0.907) or less (p = 0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9 + or - 7.9%) compared to the control group (asymmetry angle: 5.1 + or - 4.0%; p = 0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD.

In this study we report the levels of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, homovallinic acid, tryptophan, 5-hydroxyindole-3-acetic acid and serotonin in lumbar cerebrospinal fluid (CSF) from patients with multiple sclerosis, cerebrovascular disease and muscular tension headache the later, as healthy controls. The separation of these substances was performed on a reversed phase column by ion pair high performance liquid chromatography and detection was made by a glassy carbon electrode set at +900 mV vs Ag+/AgCl. The whole separation was achieved within 25 min. Concentrations of all substances (10-1000 pmole/L) were linearly proportional to areas obtained. The system is sensitive, stable and reproducible. The significance of CSF levels of these metabolites from patients groups compared with healthy controls are discussed.

Background Poor behavioural inhibition is the central impairment in attention deficit hyperactivity disorder (ADHD). At present, there is no reliable objective measure to detect ADHD. A proper pinpointing evaluation for ADHD depends mainly on the history from parents, family members as well as teachers and schoolmates, by means of questionnaires and conduct rating scales. Objective The aim of this study was to detect continuous performance task (CPT) (test of variants of attention) changes in children suffering from ADHD compared with normal children. Patients and methods CPT, Conners' parent rating scale and Wechsler intelligence scale were done for two groups of children each containing 39 children, a group of ADHD children and the other a normal control group. Results We found a significant difference between the mean total IQ score among the ADHD patients group compared with control group. Comparing both groups revealed statistically significant increase in omission, commission and reaction time among patients. A significant negative correlation was found between age on one side and IQ, hyperactivity and psychosomatic subscales, hyperactivity and total DSM-IV scores on the other hand and between commission and opposition, restlessness subscales and ADHD index and also between reaction time and restlessness and emotional index. There was a significant positive correlation between omission and hyperactivity and anxiety subscales, restlessness and emotional indices and DSM-IV hyperactive and total scores. In addition, there was a significant positive correlation between perfectionism and commission and also between reaction time and inattention and social problems subscales. Conclusion CPT can have a substantial role in objective identification of ADHD.

Background The electroencephalogram (EEG) has long been used to pick up and analyze the electrical activity of the outermost layer of the brain. Attention deficit hyperactivity disorder (ADHD) patients revealed increased power in the lower frequency bands (δ and θ power) and a raised θ/β ratio. Objective The aim of this study was to detect the quantitative EEG changes in children with ADHD compared with normal children. Patients and methods The sampled group consisted of 45 children suffering from ADHD and represented the patient group, and 45 normal children represented the control group. EEG was recorded under resting conditions for all participants. Data from frontal areas were digitally processed and analyzed to calculate the four frequency bands' power (β, α, θ, and δ) and then θ/β ratio was computed. For the patient group, the Wechsler Intelligence Scale for Children was applied and parents of these patients filled out the Arabic version of Conners' Parent Rating Scale-revised-long version. Results The patient group showed significantly higher θ/β ratio in frontal areas compared with the control group ( P P P Conclusion Quantitative EEG markers - namely, the θ/β ratio - could play a role in the understanding and identification of ADHD.

A sensitive sandwich ELISA was applied to the measurement of the terminal component of complement C9 in CSF and plasma from 40 tension headache patients (reference group), 33 affected by clinically definite MS and 10 by aseptic meningitis. The levels of C9 in plasma were increased in aseptic meningitis. The determinations of CSF/plasma C9 ratio and C9 index, equal to (CSF C9/plasma C9): (CSF albumin/plasma albumin), thus accounting for changes of plasma C9 levels as well as damaged blood brain barrier, documented the existence of local consumption of C9 in aseptic meningitis. In contrast, only borderline alterations were evident in MS. The results indicate that local consumption of total C9 in CSF is an additional variable reflecting an acute inflammation within the CNS, but not demonstrable in MS, a chronic inflammatory CNS disorder.

— The intrathecal production (ITP) of the immunoglobulins (Ig) G, A, M and D was examined in untreated patients with multiple sclerosis (MS) and controls. Sensitive sandwich enzyme-linked immunosorbent assay systems were applied to the determination of IgA, IgM and IgD levels in the cerebrospinal fluid and plasma from a group of 61 consecutive MS patients (41 relapsing-remitting and 20 secondary chronic progressive MS). Age-related reference limits for all Ig variables were defined in a group of 57 patients with tension headache. ITP of IgG was demonstrated in 85% of the MS patients, ITP of IgA in 41%, of IgM in 44% and of IgD in 18%. Among 9 MS patients with normal IgG index, 3 displayed ITP of IgA, 3 of IgM and 1 of IgD. Plasma IgA was elevated in 20% and plasma IgM in 24% of the MS cases. No significant variation of Ig ITP was demonstrated in a different group of 27 untreated MS patients examined during exacerbation and remission. Among control patients with other inflammatory nervous system diseases, ITP of IgA, IgM and IgD was found more frequently, and of IgG in a smaller percentage compared with MS patients.