Dose-response effect of L-theanine on psychomotor speed, sustained attention, and inhibitory control: a double-blind, placebo-controlled, crossover study.

BACKGROUND: L-theanine is a non-protein-forming amino acid found in tea. Previous research shows high doses (100-400 mg) of L-theanine enhances attention, mainly by reducing mind wandering and distracter processing. We hypothesized that these indirect mechanisms could significantly improve the performance of low-level attentional tasks, whereas the relative contribution could be less in complex attentional tasks that require active, higher-order processing of target stimuli. METHODS: To test this hypothesis, we conducted a double-blind, placebo-controlled, counterbalanced, four-way crossover study in 32 healthy young adults, where we compared the effects of three doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water), administered before and 50 min after dosing, on three attentional tasks from the Cambridge Neuropsychological Test Automated Battery [viz. Reaction Time (RTI)-visuomotor speed, Rapid Visual Information Processing (RVP)-sustained attention, and Stop Signal Task (SST)-inhibitory control]. Results were analyzed in dose × time repeated measures ANOVA models, with subsequent pairwise comparisons. RESULTS: Active doses significantly improved reaction times in the RTI (100-200 mg) and RVP (200-400 mg) tasks from baseline (p < 0.05), but once controlled for the change-from-baseline caused by placebo, only the RTI simple reaction times showed significant improvements, following 100 mg (Δ = 16.3 ms, p = 0.009) and 200 mg (Δ = 16.9 ms, p = 0.009) of L-theanine. CONCLUSIONS: Consistent with our hypothesis, these findings suggest that L-theanine significantly improves attention in simple visuomotor tasks, but not in more complex sustained attention tasks, or executive control tasks that require top-down inhibition of pre-active responses.

L-theanine improves neurophysiological measures of attention in a dose-dependent manner: a double-blind, placebo-controlled, crossover study.

Objective: L-theanine, a non-proteinic amino acid found in tea, is known to enhance attention particularly in high doses, with no reported adverse effects. We aimed to determine whether oral administration of L-theanine acutely enhances neurophysiological measures of selective attention in a dose-dependent manner.Methods: In a double-blind, placebo-controlled, counterbalanced, 4-way crossover study in a group of 27 healthy young adults, we compared the effects of 3 doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water) on latencies of amplitudes of attentive and pre-attentive cognitive event-related potentials (ERPs) recorded in an auditory stimulus discrimination task, before and 50 min after dosing.Results: Compared to the placebo, 400 mg of theanine showed a significant reduction in the latency of the parietal P3b ERP component (p < 0.05), whereas no significant changes were observed with lower doses. A subsequent exploratory regression showed that each 100-mg increase in dose reduces the P3b latency by 4 ms (p < 0.05). No dose-response effect was observed in P3b amplitude, pre-attentive ERP components or reaction time.Discussion: The findings indicate L-theanine can increase attentional processing of auditory information in a dose-dependent manner. The linear dose-response attentional effects we observed warrant further studies with higher doses of L-theanine.

Changes of attention-related brain activity over 6 months after acute organophosphate pesticide poisoning: a prospective follow-up study.

CONTEXT: Ingestion of organophosphate (OP) pesticides is a common method of self-harm in developing countries. Apart from acute cholinergic effects, limited evidence implicates OP poisoning in long-term neurocognitive deficits. However, prospective neurophysiological evidence of long-term deficits is scarce in humans. We aimed to determine long-term cognitive changes of acute OP pesticide self-poisoning in a prospective follow-up study, using event-related potentials (ERPs), an electroencephalographic index of cognitive functioning. METHODS: We recruited 203 patients (147 men) hospitalised with OP pesticide ingestion (OP group; all had significant erythrocyte cholinesterase inhibition) and 50 patients (23 men) with paracetamol overdose (control group) as a means of self-harm. We recorded their ERPs and behavioural performance in a selective attention task at three post-exposure time points: on discharge from hospital (around 14 days post-ingestion), 6 weeks and 6 months post-ingestion. We compared the reaction time and ERP components of the two groups at each time point, adjusting for sex, age, education and comorbid depression in multiple regression models. RESULTS: OP group had significantly slower reaction times than the control group on discharge and at 6 weeks, but not at 6 months. On discharge, the OP group also showed significantly prolonged latency of the parietal P3b component, signifying delayed attentional processing. P3b amplitudes were also significantly smaller in the OP group on discharge and at 6 months. Within the OP group, greater clinical severity of poisoning was associated with smaller P3b amplitudes. Early pre-attentive cortical processing (as indexed by N1 ERP component) showed no significant intergroup differences. CONCLUSIONS: Acute OP pesticide poisoning was associated with impaired behavioural and neurophysiological indices of selective attention. These deficits outlast the cholinergic phase of intoxication. The neurobehavioral impairment disappears over months, but neurophysiological deficits seem to last even after 6 months. This impairment could potentially compromise the performance and safety of patients for months following clinical recovery.

The effect of optic neuritis treatment trial (ONTT) combined corticosteroid regimen on pattern reversal visual evoked potentials: a prospective follow-up study.

BACKGROUND: The combined corticosteroid regimen of the original Optic Neuritis Treatment Trial (ONTT) is used in many centers to treat optic neuritis. Though pattern reversal visual evoked potentials (PRVEPs) are a sensitive, standard measure of visual conduction in optic neuritis, no studies hitherto have investigated the effect of combined ONTT regimen on PRVEPs. We aimed to determine the effect of combined corticosteroid regimen of the ONTT on changes of PRVEPs in patients with first-episode optic neuritis over 3 months post-treatment. METHODS: This is a prospective, observational study in which 44 patients with optic neuritis were seen pre-treatment (baseline) and follow-up, at 1 month (FU1) and 3 months (FU2). Twenty-nine patients were treated with ONTT combined regimen (ONTT+ Group) while 15 were conservatively managed without corticosteroids (ONTT- Group). The median latency and amplitude values of the P100 PRVEP component and the visual acuity (i.e. LogMAR values) at pre-treatment, FU1 and FU2 were compared in the two groups using Friedman's rank test and Wilcoxon Signed Ranks test. RESULTS: Median P100 latency improved significantly (to the normal range) as early as by 1 month after the commencement of treatment in the ONTT+ Group, and then remained significantly lower than the baseline over next 2 months. In the ONTT- Group, the median P100 latency improved more slowly over the two follow up assessments and reached the normal range by 3 months. Median visual acuity values also improved significantly at 1 and 3 months after the commencement of treatment in the ONTT+ Group but not in the ONTT- Group. CONCLUSION: ONTT combined corticosteroid regimen improves conduction in the visual pathways of patients with first-episode optic neuritis earlier than does conservative management. We provide electrodiagnostic evidence that combined ONTT regimen-compared with conservative management-results in early remission of visual conduction abnormalities in first-episode optic neuritis.

Subacute and chronic neuropsychological sequalae of acute organophosphate pesticide self-poisoning: a prospective cohort study from Sri Lanka.

CONTEXT: Some epidemiological evidence implicates acute organophosphate (OP) pesticide poisoning in long-term neurocognitive deficits. However, no study has prospectively followed up poisoned patients long-term from the time of intoxication. We aimed to determine whether clinically significant acute OP self-poisoning leads to subacute and chronic neurocognitive deficits, in a prospective follow up study. METHODS: Employing Mini Mental State Examination, Digit Span and Cambridge Neuropsychological Test Automated Battery (CANTAB), we compared multiple cognitive functions in 222 patients hospitalized with acute OP pesticide self-poisoning with a control group of 52 patients hospitalized with paracetamol overdose, at three time points: on discharge following clinical recovery, 6 weeks and 6 months post-ingestion. Intergroup comparisons at each time point were done in multiple regression models, adjusting for sex, age, education and psychiatric comorbidities. OP within-group analysis was done to determine a dose-response relationship. RESULTS: After adjusting for covariates, the OP poisoned group had significantly poorer working memory (Digit Span) and episodic memory (CANTAB Paired Associates Learning); impaired spatial planning (CANTAB Stocking of Cambridge); and slower response speed in the sustained attention task (CANTAB Rapid Visual Information Processing), in the post-discharge assessment. Only working memory and episodic memory measures were impaired in the OP group at 6 weeks, whereas no significant intergroup differences were observed at 6 months. The OP subgroup who had complete red cell acetylcholinesterase inhibition on admission had poorer episodic memory when tested post-discharge than those who had partial inhibition, but no significant subgroup differences were observed at 6 weeks or 6 months. DISCUSSION: Acute OP pesticide poisoning may cause neuropsychological impairment that outlasts the cholinergic phase on a subacute time scale; but does not cause measurable chronic neuropsychological deficits.

Dysfunction in macula, retinal pigment epithelium and post retinal pathway in acute organophosphorus poisoning.

CONTEXT: Organophosphorus (OP) insecticide poisoning is a significant health problem in South Asian countries. Although cholinergic receptors are present at the junction between photoreceptors and the retinal pigment epithelium (RPE), human studies of the effects of OP poisoning on the visual pathways are very few. This study aims to demonstrate the pattern of changes in retina and post retinal pathways in patients with acute OP poisoning using visual electrophysiological tests. METHODS: This is an observational, cross-sectional study conducted at the Neurophysiology Unit, Teaching Hospital, Peradeniya, Sri Lanka. We tested 16 patients recovered from cholinergic phase, at least 24 h after deatropinization and within 8 weeks of OP ingestion. We assessed the functional integrity of the photoreceptors and ganglion cells of the macula by pattern electroretinography (PERG); RPE by electro-oculography (EOG); and post retinal pathways by pattern reversal visual evoked potentials (PR-VEP). Latencies and amplitudes of PR-VEP and PERG, light peak (LP), dark trough (DT) and Arden ratio of EOG were determined in patients and compared with 16 controls using the Mann-Whitney U test. RESULTS: Of the 16 OP-poisoned patients (median age of 37 ± IQR 20 years), six (37.5%) had reduced Arden ratio with reference to the International Society of Clinical Electrophysiology of Vision cut-off value of 1.7. The median Arden ratio in patients (1.69 ± IQR 0.36) was significantly lower compared to controls (1.90 ± IQR 0.4). The median latencies and amplitudes of PR-VEP or PERG were not significantly different between patients and controls. However, three patients had prolonged P100 latencies in PR-VEP and one had prolonged P50 latency in PERG. CONCLUSIONS: Acute OP poisoning seems to affect the functions of the RPE and the visual electrophysiological changes outlast the cholinergic phase. Limited evidence suggests that photoreceptors of the macula region and post retinal pathway might be affected in some patients.

Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.

We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task ~ 1 h post-dose. NIH Cognition Toolbox was administered ~ 2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. L-Theanine improved total cognition composite in NIH Cognition Toolbox (p = 0.040) vs. placebo. Caffeine worsened and L-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p = 0.031 and p = 0.053 respectively). L-Theanine-caffeine combination improved total cognition composite (p = 0.041), d-prime in the Go/NoGo task (p = 0.033) and showed a trend of improvement of inhibitory control (p = 0.080). L-Theanine-caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). L-Theanine-caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.

Differences between organophosphates in respiratory failure and lethality with poisoning post the 2011 bans in Sri Lanka.

Introduction: Self-poisoning with organophosphorus pesticides (OPs) has high morbidity and mortality. The most toxic OP formulations have been progressively banned in Sri Lanka over the past three decades. However, respiratory failure (RF) requiring ventilation remains a major contributor to fatalities. Therefore, this study was conducted to examine the frequency of RF and death after poisoning with the currently available OPs to determine if further bans might be warranted to reduce the burden of OP poisoning in Sri Lanka.Methods: Five hundred and forty patients with confirmed OP self-poisoning were prospectively observed throughout their hospital stay following admission to Peradeniya hospital in the Central Province of Sri Lanka. Clinical data including the time and duration of intubation were documented prospectively in structured datasheets.Results: One hundred and forty-nine patients required ventilation (27%), and 34 (23%) of those died. Males with alcohol co-ingestion were more likely to develop RF. Compared to other OPs, profenofos (Odds Ratio [OR] = 2.5, 95% CI: 1.5-3.9), and quinalphos (OR = 4.5, 95% CI: 1.6-12.6) were more likely to, and chlorpyrifos (OR = 0.2, 95% CI: 0.1-0.4) less likely to lead to RF than other OPs. Profenofos was also associated with higher mortality (OR = 2.3, 95% CI: 1.1-4.6) than other OPs. The median time to intubation was longer for profenofos, but the duration of intubation was similar for all OP formulations.Conclusion: RF and deaths following OP ingestion continue to be a major problem in Sri Lanka, with profenofos being the major current agent of concern. Strategies to replace profenofos and quinalphos use with less toxic insecticides should be explored. Doctors should be alert to the high probability of delayed and prolonged RF after profenofos poisoning.

Prediction of organophosphorus insecticide-induced intermediate syndrome with stimulated concentric needle single fibre electromyography.

BACKGROUND: Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to over-activity of muscarinic and nicotinic cholinergic circuits. Intermediate syndrome (IMS) is mediated via prolonged nicotinic receptor stimulation at the neuromuscular junction and its onset is between 24-96 hours post ingestion. The aims of the present study were 1) to investigate whether neuromuscular junction dysfunction within the first 24 hours following exposure, quantified by jitter in single fibre electromyography (SfEMG), can predict IMS, and 2) to compare the changes in SfEMG jitter over the course of the illness among patients who developed IMS (IMS+) and those who did not (IMS-). METHODS AND FINDINGS: We conducted a prospective cohort study in a tertiary care hospital in Sri Lanka on 120 patients admitted between September 2014 and August 2016 following DSP by OP insecticides viz., profenofos 53, phenthoate 17, diazinon 13, chlorpyrifos 5, others 12, unknown 20. SfEMG was performed every second day during hospitalization. Exposure was confirmed based on the history and red blood cell AChE assays. IMS was diagnosed in patients who demonstrated at least three out of four of the standard IMS criteria: proximal muscle weakness, bulbar muscle weakness, neck muscle weakness, respiratory paralysis between 24-96 hours post ingestion. Respiratory failure requiring intubation occurred in 73 out of 120 patients; 64 of these were clinically diagnosed with IMS. Of the 120 patients, 96 had repeated SfEMG testing, 67 of them being tested within the first 24 hours. Prolonged jitter (>33.4µs) within the first 24 hours was associated with greatly increased risk of IMS (odds ratio = 8.9, 95% confidence intervals = 2.4-29.6, p = 0.0003; sensitivity 86%, specificity 58%). The differences in jitter between IMS+ and IMS- patients remained significant for 72 hours and increased jitter was observed in some patients for up to 216 hours. For intubated patients, the median time for jitter to normalize and median time to extubate were similar, and the two variables had a moderate positive correlation (r = 0.49, P = 0.001). CONCLUSIONS: Prolonged jitter recorded with SfEMG <24 hours of ingestion of an OP strongly correlates with subsequent occurrence of IMS. The time course of electrophysiological recovery of the NMJ was similar to the time course of respiratory recovery in IMS patients.

l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study.

Oral intake of l-theanine and caffeine supplements is known to be associated with faster stimulus discrimination, possibly via improving attention to stimuli. We hypothesized that l-theanine and caffeine may be bringing about this beneficial effect by increasing attention-related neural resource allocation to target stimuli and decreasing deviation of neural resources to distractors. We used functional magnetic resonance imaging (fMRI) to test this hypothesis. Solutions of 200mg of l-theanine, 160mg of caffeine, their combination, or the vehicle (distilled water; placebo) were administered in a randomized 4-way crossover design to 9 healthy adult men. Sixty minutes after administration, a 20-minute fMRI scan was performed while the subjects performed a visual color stimulus discrimination task. l-Theanine and l-theanine-caffeine combination resulted in faster responses to targets compared with placebo (∆=27.8milliseconds, P=.018 and ∆=26.7milliseconds, P=.037, respectively). l-Theanine was associated with decreased fMRI responses to distractor stimuli in brain regions that regulate visual attention, suggesting that l-theanine may be decreasing neural resource allocation to process distractors, thus allowing to attend to targets more efficiently. l-Theanine-caffeine combination was associated with decreased fMRI responses to target stimuli as compared with distractors in several brain regions that typically show increased activation during mind wandering. Factorial analysis suggested that l-theanine and caffeine seem to have a synergistic action in decreasing mind wandering. Therefore, our hypothesis is that l-theanine and caffeine may be decreasing deviation of attention to distractors (including mind wandering); thus, enhancing attention to target stimuli was confirmed.

Acute effects of theanine, caffeine and theanine-caffeine combination on attention.

OBJECTIVE: l-theanine is a constituent of tea which is claimed to enhance cognitive functions. We aimed to determine whether theanine and theanine-caffeine combination have acute positive effects on cognitive and neurophysiological measures of attention, compared to caffeine (a positive control) and a placebo in healthy individuals. DESIGN: In a placebo-controlled, five-way crossover trial in 20 healthy male volunteers, we compared the effects of l-theanine (200 mg), caffeine (160 mg), their combination, black tea (one cup) and a placebo (distilled water) on cognitive (simple [SVRT] and recognition visual reaction time [RVRT]) and neurophysiological (event-related potentials [ERPs]) measures of attention. We also recorded visual (VEPs) and motor evoked potentials (MEPs) to examine any effects of treatments on peripheral visual and motor conduction, respectively. RESULTS: Mean RVRT was significantly improved by theanine (P = 0.019), caffeine (P = 0.043), and theanine-caffeine combination (P = 0.001), but not by tea (P = 0.429) or placebo (P = 0.822). VEP or MEP latencies or SVRT did not show significant inter-treatment differences. Theanine (P = 0.001) and caffeine (P = 0.001) elicited significantly larger mean peak-to-peak N2-P300 ERP amplitudes than the placebo, whereas theanine-caffeine combination elicited a significantly larger mean N2-P300 amplitude than placebo (P < 0.001), theanine (P = 0.029) or caffeine (P = 0.005). No significant theanine × caffeine interaction was observed for RVRT or N2-P300 amplitude. DISCUSSION: A dose of theanine equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses.

Task-specific kinetic finger tremor affects the performance of carrom players.

We aimed to determine the effect of task-specific kinetic finger tremor, as indexed by surface electromyography (EMG), on the accuracy of a carrom stroke. Surface EMG of extensor digitorum communis muscle of the playing arm was recorded during rest, isometric contraction and stroke execution in 17 male carrom players with clinically observed finger tremor and 18 skill- and age-matched controls. Log-transformed power spectral densities (LogPSDs) of surface EMG activity (signifying tremor severity) at a 1-s pre-execution period correlated with angular error of the stroke. LogPSDs in 4-10 Hz range were higher in players with tremor than controls during pre-execution (P < 0.001), but not during the resting state (P = 0.067). Pre-execution tremor amplitude correlated with angular deviation (r = 0.45, P = 0.007). For the first time, we document a task-specific kinetic finger tremor in carrom players. This finger tremor during the immediate pre-execution phase appears to be a significant determinant of stroke accuracy.

Physiological changes during and outcome following 'filtration' based continuous plasma exchange in Guillain Barre Syndrome.

BACKGROUND: Therapeutic plasma exchange is an extracorporeal blood purification technique designed for the removal of large molecular weight substances from plasma. It is the first line treatment in Guillain Barre Syndrome (GBS) improving outcome. AIM: To study the outcome in GBS following therapeutic plasma exchange (TPE) utilizing a modified, cost saving, filtration based plasma exchange technique. METHODOLOGY AND FINDINGS: Consenting patients with GBS underwent TPE using a modified regime of two 48 h sessions as a cost saving strategy. The second session was conducted only if there was inadequate benefit from the first session. Nerve conduction studies confirmed the diagnosis of GBS. RESULTS: Fifteen patients were studied. One died following a cerebro-vascular accident. Of the remaining 14 patients, five showed improvement in muscle power at least by one grade in one limb within 48 h of plasma exchange. The duration of intensive care unit stay was 10 (median) days (range 4-66). Nine required mechanical ventilation for (median) 15 days (range 4-50). The mean 24h urine output increased significantly since the initiation of plasma exchange was 6262.92 ml (SD=8867.24, P=0.032) at 48 h and 6474.92 ml at 72 h (SD=6364.81, P=0.003). The pulse rates and blood pressures were not significantly different before and after plasma exchange. Complications attributable to plasma exchange were mild; a hypersensitivity reaction and a tendency to ooze from a puncture site. CONCLUSION: 'Continuous' TPE, the modified cost saving technique seems to improve the outcome of patients with Guillain Barre Syndrome with minimal complications.

Abnormal parameters of magnetically evoked motor-evoked potentials in patients with cervical spondylotic myelopathy.

BACKGROUND CONTEXT: Magnetic stimulation (MS), which is used to evaluate motor pathways, is helpful in evaluating cervical spinal cord compression (cervical myelopathy [CM]). Previous studies have shown that the central motor conduction time (CMCT), which is the time taken for the nerve impulses to reach the cervical spinal roots after the stimulation of the motor cortex, is prolonged in CM. However, the duration of motor-evoked potentials (MEPs) in CM has not been studied in detail. PURPOSE: To compare the duration, CMCT and amplitude of MEPs by MS between patients with clinical and magnetic resonance imaging (MRI) features of CM and a control group. STUDY DESIGN/SETTING: A cross-sectional study done at Teaching Hospital, Peradeniya, Sri Lanka. PATIENT SAMPLE: Consecutive patients with clinical features of cervical spondylotic myelopathy, without coexisting neurological abnormality. METHODS: Transcranial and cervical spinal magnetic stimulation were performed on 21 patients with clinical and MRI features of spondylotic CM (mean age, 43.5years; range, 36-63 years; 9 men) and 17 healthy volunteers (mean age, 39.05 years; range, 23-54yrs; 6 males) using a circular coil with a Magstim 200 stimulator. MEPs were recorded over abductor digiti minimi muscle on both hands. RESULTS: Seventeen patients had upper motor neuron (UMN) features in all four limbs; in the others, both lower limbs and one upper limb were affected. The upper limbs with UMN features had shorter duration MEPs compared with the control group. The CMCT and the total motor conduction time were also delayed in the CM group. All three differences were very highly significant (t=5.75, -3.76, 5.27; p<.001). The amplitudes showed no significant difference between the two groups (t=1.27, p=.208). CONCLUSION: This study shows that in addition to the CMCT, the duration of MEPs is also useful in evaluating patients with CM using MS.