Differentiating responders and non-responders to rTMS treatment for depression after one week using resting EEG connectivity measures.

BACKGROUND: Non-response to repetitive transcranial magnetic stimulation (rTMS) treatment for depression is costly for both patients and clinics. Simple and cheap methods to predict response would reduce this burden. Resting EEG measures differentiate responders from non-responders, so may have utility for response prediction. METHODS: Fifty patients with treatment resistant depression and 21 controls had resting electroencephalography (EEG) recorded at baseline (BL). Patients underwent 5-8 weeks of rTMS treatment, with EEG recordings repeated at week 1 (W1). Forty-two participants had valid BL and W1 EEG data, and 12 were responders. Responders and non-responders were compared at BL and W1 in measures of theta (4-8 Hz) and alpha (8-13 Hz) power and connectivity, frontal theta cordance and alpha peak frequency. Control group comparisons were made for measures that differed between responders and non-responders. A machine learning algorithm assessed the potential to differentiate responders from non-responders using EEG measures in combination with change in depression scores from BL to W1. RESULTS: Responders showed elevated theta connectivity across BL and W1. No other EEG measures differed between groups. Responders could be distinguished from non-responders with a mean sensitivity of 0.84 (p = 0.001) and specificity of 0.89 (p = 0.002) using cross-validated machine learning classification on the combination of all EEG and mood measures. LIMITATIONS: The low response rate limited our sample size to only 12 responders. CONCLUSION: Resting theta connectivity at BL and W1 differ between responders and non-responders, and show potential for predicting response to rTMS treatment for depression.

Responders to rTMS for depression show increased fronto-midline theta and theta connectivity compared to non-responders.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction. PRIMARY HYPOTHESES: We expected higher theta and alpha activity in responders compared to non-responders to rTMS. METHODS: Fifty patients with treatment resistant depression and twenty controls performed a WM task while electroencephalography (EEG) was recorded. Patients underwent 5-8 weeks of rTMS treatment, repeating the EEG at week 1 (W1). Of the 39 participants with valid WM-related EEG data from baseline and W1, 10 were responders. Comparisons between responders and non-responders were made at baseline and W1 for measures of theta (4-8 Hz), upper alpha (10-12.5 Hz), and gamma (30-45 Hz) power, connectivity, and theta-gamma coupling. The control group's measures were compared to the depression group's baseline measures separately. RESULTS: Responders showed higher levels of WM-related fronto-midline theta power and theta connectivity compared to non-responders at baseline and W1. Responder's fronto-midline theta power and connectivity was similar to controls. Responders also showed an increase in gamma connectivity from baseline to W1, with a concurrent improvement in mood and WM reaction times. An unbiased combination of all measures provided mean sensitivity of 0.90 at predicting responders and specificity of 0.92 in a predictive machine learning algorithm. CONCLUSION: Baseline and W1 fronto-midline theta power and theta connectivity show good potential for predicting response to rTMS treatment for depression.

Emotive interference during cognitive processing in major depression: an investigation of lower alpha 1 activity.

BACKGROUND: Individuals with Major Depressive Disorder (MDD) tend to be more susceptible to distraction by negative emotional material than their non-depressed counterparts. This extends to an enhanced vulnerability to interference from mood-congruent stimuli during cognitive processing. The current study investigated the electrophysiological correlates of competing cognitive and emotional processing demands in MDD. METHODS: Event-related alpha activity within the lower alpha 1 band was examined during the online information retention phase of a non-emotive WM task with extraneous emotional stimuli (positive, negative and neutral) presented as background images. EEG activity over posterior parietal cortex was compared between 15 acutely depressed and 16 never depressed right-handed women. RESULTS: A valence specific dissociation in lower alpha 1 activity was observed between the two groups, consistent with greater attentional resource allocation to positive distracters in control participants and to negative distracters in MDD participants. No group differences were seen when neutral distracters were displayed. CONCLUSIONS: These results demonstrate that activity within the lower alpha 1 band is sensitive to competing emotional and cognitive processing demands and highlight the importance of posterior parietal regions in depression-related susceptibility to affective distractibility during cognitive processing.

Individualized alpha activity and frontal asymmetry in major depression.

Lateralized differences in frontal alpha power in individuals with major depressive disorder (MDD) are thought to reflect an aberrant affective processing style. However research into anterior alpha asymmetry and MDD has often produced conflicting results. The current study aimed to investigate whether individualized alpha bandwidths provide a more sensitive measure of anterior alpha asymmetry in MDD than the traditional fixed 8-13 Hz alpha band. Resting EEG was recorded from 34 right-handed female participants (18 controls, 16 MDD). Each participant's Individual Alpha Frequency was used to delineate a broad individualized alpha band and three individualized narrow alpha sub-bands: lower alpha1, lower alpha 2 and upper alpha. Activity within the broad and narrow individualized bandwidths and within the traditional fixed alpha band were used to compare a) controls and acutely depressed individuals and b) medicated and unmedicated MDD participants. Individualizing and subdividing the alpha bandwidth did not add appreciably to the sensitivity of anterior alpha asymmetry in MDD as no significant differences in lateralized alpha power between controls and MDD participants were observed in any alpha bandwidth. This finding was consistent under two reference schemes and across multiple scalp locations. Within the MDD group, antidepressant use was associated with significantly greater right than left hemispheric power in the lower alpha 1 band. The relevance of this finding is discussed in relation to the electrophysiological correlates of antidepressant medication use, lateralized differences in affective processing and treatment resistant MDD.

Upper alpha activity during working memory processing reflects abnormal inhibition in major depression.

BACKGROUND: EEG studies examining 'resting' state (i.e. non-task) state brain activity in major depressive disorder (MDD) have reported numerous abnormalities within the alpha bandwidth. These findings are discussed extensively within affective disorders literature but their relationship to functional aspects of depressive psychopathology remains unclear. Investigating alpha modulation during active cognitive processing may provide a more targeted means of relating aberrant alpha activity to specific aspects of depression symptomatology. Alpha activity is reliably modulated during working memory (WM) processing and WM impairments are a common neuropsychological consequence of MDD. Moreover, it has been suggested that alpha activity reflects internally mediated inhibitory process and attenuated inhibition has been suggested to contribute to WM inefficacy. AIM: The current investigation examined whether alpha was modulated differently in MDD participants during WM processing and whether the pattern of alpha activity was consistent with impairments in inhibitory processes. METHOD: Event related synchronisation (ERS) within the upper alpha band over the retention interval of a modified Sternberg WM task was examined in 15 acutely depressed and 15 never depressed right-handed female participants. RESULTS: MDD participants displayed greater upper alpha ERS than controls during the online information maintenance component of WM processing. This was evident over left, but not right, parieto-occipital cortex. CONCLUSION: The results are consistent with increased inhibition of extraneous material during WM processing in depression. This may reflect a neurobiological compensation strategy whereby additional neural resources are required to achieve comparable performance accuracy during effortful cognitive processing in MDD.

The effect of test TMS intensity on short-interval intracortical inhibition in different excitability states.

The paired-pulse transcranial magnetic stimulation (TMS) paradigm is increasingly employed to examine intracortical inhibitory processes in different motor tasks. Short-interval intracortical inhibition (SICI) has been shown to vary with the size of the MEP elicited by the test TMS pulse. This suggests that factors that alter MEP size, such as changes in cortical excitability, may confound the interpretation of SICI. However, the effect of excitability on SICI has not been systematically investigated. The present study examined SICI in 11 volunteers. The effect of test TMS intensities ranging from 90 to 150% resting motor threshold (RMT) on SICI was examined in three excitability states in the right first dorsal interosseous muscle: rest, isometric abduction of the left index finger (Contra) and isometric abduction of the right index finger (Active). For all excitability states SICI was not observed when test TMS intensity was less than 110% resting motor threshold. This was true even for the Active condition in which 90 and 100% test TMS intensities elicited large and consistent MEPs. For all conditions moderately suprathreshold test TMS intensities (110-120% RMT) yielded the greatest measure of SICI; increasing test TMS intensities resulted in a progressive reduction in the estimate of SICI. These results suggest that estimates of SICI are systematically affected by the intensity of the test TMS pulse, regardless of excitability state. The results suggest that SICI should be examined using a constant test TMS intensity regardless of changes in cortical excitability and test MEP size.

Distribution of naturally occurring quinones.

Angiosperms, fungi (including lichens), and bacteria are the main sources of natural quinones. Small numbers are present in algae, ferns, conifers, sponges, echinoderms, other marine animals, and arthropods. In angiosperms quinones have some chemotaxonomic value at the genus and family level but more surveys are required.

Factors affecting the survival of Salmonella and Escherichia coli in anaerobically fermented pig waste.

The survival of Salmonella typhimurium was investigated in acidogenic, anaerobically fermented pig wastes and in synthetic media, each containing volatile fatty acids (VFA). Salm. typhimurium survived at pH 6.8, but not at pH 4.0, when incubated at 37 degrees C for 24 h in either fermented or synthetic medium containing VFA. The minimum inhibiting concentration of VFA for Salm. typhimurium after 48 h incubation at 30 degrees C at pH 4.0 was 0.03 mol/l and for Escherichia coli it was 0.09 mol/l. Fermented pig wastes in a digester, maintained at pH 5.9, were inoculated with Salm. typhimurium and then incubated at 37 degrees C for 24 h. The pH was adjusted to either 4.0 or 5.0 and after a further 48 h at 30 degrees C, Salm. typhimurium survived at pH 5.0 but not at pH 4.0. It was concluded that pH is critical in determining the survival of this organism in acidogenic anaerobically fermented pig waste.

5,8-dihydroxyflavone (primetin) the contact sensitizer of Primula mistassinica Michaux.

5,8-Dihydroxyflavone (primetin) has been shown to be the sensitizer in Primula mistassinica Michaux and probably the source of allergic contact dermatitis in four milkers. Its sensitizing properties as determined in guinea-pigs, are strong. As far as is known this is the first experimental demonstration of the sensitizing potency of a flavone. Presumably the flavone, with its uncommon 5,8-arrangement of hydroxy groups, is oxidized in the skin to the corresponding quinone (primetinquinone). Quinone was prepared from primetin and used for experimental sensitization of guinea-pigs. It also revealed strong sensitizing properties. Cross-reactions were obtained not only with the synthetic quinone in the flavone-sensitive animals but also with primetin in primetinquinone-sensitive guinea-pigs. Preliminary sensitization tests with other flavones have demonstrated that the whole group of flavonoid components should be taken into consideration as potential sensitizers.

Gadusol, an enolic derivative of cyclohexane-1,3-dione present in the roes of cod and other marine fish. Isolation, properties and occurrence compared with ascorbic acid.

Gadusol, C8H12O6, has been isolated from roes of the cod (Gadus morhua L.), i.e., ovaries that contain ripe eggs just before spawning. The concentration is about 4 g/kg dry wt. It has been identified as 1,4,5-trihydroxy-5-hydroxymethyl-2-methoxycyclo-hex-1-en-3-one and this structure was confirmed by synthesis of the anhydro tetra-acetate derivative from methyl 3,5-diacetoxy-4-methoxybenzoate. Concentrations of gadusol in the roes of other marine teleost fish examined are of the same order as in cod roes. Gadusol has some properties similar to ascorbic acid and both compounds, after oxidation, react with 2,4-dinitrophenylhydrazine in the commonly-used assay procedure for ascorbic acid. Specific assays showed that the concentrations of gadusol in the roes of marine fish are severalfold greater than those of ascorbic acid. Gadusol is structurally related to the mycosporines previously reported from a number of different organisms.

Growth of Candida ingens on Supernatant from Anaerobically Fermented Pig Waste: Effects of Temperature and pH.

Candida ingens, a pellicle-forming yeast utilizing volatile fatty acids, grew over a pH range of 4.1 to 6.0 on nonsterile supernatants from anaerobically fermented pig wastes; growth was inconsistent between pH 4.1 and 4.6. When ambient temperature above the pellicle was 21 degrees C and the temperature of the medium was 29 to 32 degrees C, a pH range of 4.8 to 5.0 gave yields of 1.90 to 3.31 g of dry matter per liter, and 0.059 to 0.065 mol of volatile fatty acids was utilized per liter. There was no advantage in utilization of volatile fatty acids and yield of dry matter in keeping the pH constant during a 24-h growth period. C. ingens grew at pH 4.8 and 5.0 when both ambient and medium temperatures were 30 degrees C. When ambient temperature was 10 degrees C, maximum yield and utilization of volatile fatty acids occurred at a medium temperature of 28 to 30 degrees C.

Study of Candida ingens grown on the supernatant derived from the anaerobic fermentation of monogastric animal wastes.

A pellicle-forming yeast, identified as Candida ingens, was found to grow on substrates derived from the anerobic fermentation of monogastric animal wastes. The organism used volatile fatty acids C2 to C6 and ammonia nitrogen. It had a preferential uptake of the acids in increasing order of molecular weight, removing 90% of the total titratable volatile acid. The nonwrinkled pellicle had a doubling time of 3.2 h, and the doubling time of the wrinkled pellicle was 4.2 h. Proximate amino acid and nucleic acid analyses suggested that the organism might be acceptable as a source of single cell protein. Its vitamin B group content compared favorably with that of other yeasts. It contained 6% calcium and 7% phosphorus. It could be useful in removing these minerals from effluents as well as in providing them as nutrients in livestock rations.