Psychophysiological Effects of Zembrin<sup>®</sup>Using Quantitative EEG Source Density in Combination with Eye-Tracking in 60 Healthy Subjects. A Double-Blind, Randomized, Placebo-Controlled, 3-Armed Study with Parallel Design — Oak Academic Publishing
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Psychophysiological Effects of Zembrin<sup>®</sup>Using Quantitative EEG Source Density in Combination with Eye-Tracking in 60 Healthy Subjects. A Double-Blind, Randomized, Placebo-Controlled, 3-Armed Study with Parallel Design
Justus-Liebig-University, Giessen, Germany
,
HG&H Pharmaceuticals (Pty) Ltd., Bryanston, South Africa
,
NeuroCode AG, Wetzlar, Germany
,
NeuroCode AG, Wetzlar, Germany
1 Justus-Liebig-University, Giessen, Germany
2 HG&H Pharmaceuticals (Pty) Ltd., Bryanston, South Africa
The endemic South African succulent plant Sceletium tortuosum (L.) N.E. Br., family Mesembryathemaceae, is known as kanna in Nama, kougoed in Afrikaans, and sceletium in English. The plant has been used as a tea and as a masticatory for millennia by indigenous San hunter-gatherers and Nama pastoralists for endurance and well-being. It has been reported that the plant “gives strength to their limbs, and takes away pain, and makes their memory strong”. The current investigation aimed at the psychophysiological characterization of 25.0 and 50.0 mg of a special extract marketed as Zembrin ® in comparison to placebo using a new methodology called “EnkephaloVision”. This combination of EEG Neurocode-Tracking and Eye-Tracking allows for concomitant analysis of time epochs of only 364 ms duration. Spectral EEG analysis during cognitive and emotional challenges revealed statistically significant increases of delta (p ® within the frontal brain. It is these same increases of slow waves in the frontal brain that are described in the literature during performance of mental tests. This indicates a positive effect of Zembrin ® on the electrical activity of the brain during cognitive processing. In addition, alpha1 and alpha2 spectral power in the frontal brain was increased during several challenges including brain teasing, arithmetic calculations and performance of a memory test. From the literature, increases of spectral alpha1 power indicate a greater degree of calmness and may represent decreased depressive symptoms, while increases in alpha2 waves have been related to memory. Beta2 waves increased during mental performance in the presence of the higher dosage of Zembrin ® in parietal, occipital and temporal brain regions. In comparison to placebo, Zembrin ® induced frequency changes in the brain, which have been related to enhanced attention and memory. These results may represent a positive action of Zembrin ® on cognitive and emotional processes in the brain.
Waterhouse, G., De Wet, G.C., Pheiffer, R.H. (1979) Simon van der Stel’s Journey to Namaqualand in 1685. Human & Rousseau, Cape Town.
Kolben, P. (1738) The Present State of the Cape of Good Hope. In: Medley, G., Trans., Innys, W. and Matiby, R., Eds., Vol. 1, 2nd Edition, London.
M.S.S. BC151 006 (1873) Bleek and Lloyd Collection, Manuscript and Archives Department of the University of Cape Town.
Harvey, A.L., Young, L.C., Viljoen, A.M. and Gericke, N.P. (2011) Pharmacological Actions of the South African Medicinal and Functional Food Plant Sceletium tortuosum and Its Principal Alkaloids. Journal of Ethnopharmacology, 137, 1124-1129. http://dx.doi.org/10.1016/j.jep.2011.07.035
Dimpfel, W., Schombert, L. and Gericke, N. (2016) Electropharmacogram of Sceletium tortuosum Extract Based on Spectral Local Field Power in Conscious Freely Moving Rats. Journal of Ethnopharmacology, 177, 140-147. http://dx.doi.org/10.1016/j.jep.2015.11.036
Murbach, T.S., Hirka, G., Szakonyiné, I.P., Gericke, N. and Endres, J.R. (2014) A Toxicological Safety Assessment of a Standardized Extract of Sceletium tortuosum (Zembrin ® ) in Rats. Food and Chemical Toxicology, 74, 190-199. http://dx.doi.org/10.1016/j.fct.2014.09.017
Nell, H., Siebert, M., Chellan, P. and Gericke, N. (2013) A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of Extract Sceletium tortuosum (Zembrin) in Healthy Adults. The Journal of Alternative and Complementary Medicine, 19, 898-904. http://dx.doi.org/10.1089/acm.2012.0185
Terburg, D., Syal, S., Rosenberger, L.A., Heany, S., Phillips, N., Gericke, N., Stein, D.J. and van Honk, J. (2013) Acute Effects of Sceletium tortuosum (Zembrin), a Dual 5-HT Reuptake and PDE4 Inhibitor, in the Human Amygdala and Its Connection to the Hypothalamus. Neuropsychopharmacology, 38, 2708-2716. http://dx.doi.org/10.1038/npp.2013.183
Chiu, S., Gericke, N., Farina-Woodbury, M., Badmaev, V., Raheb, H., Terpstra, K., Antongiorgi, J., Bureau, Y., Cernovsky, Z., Hou, J., Sanchez, V., Williams, M., Copen, J., Husni, M. and Goble, L. (2014) Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia. Evidence-Based Complementary and Alternative Medicine, 2014, Article ID: 682014. http://dx.doi.org/10.1155/2014/682014
Christian, E.P., Snyder, D.H., Song, W., DaGurley, D.A., Smolka, J., Maier, D.L., Ding, M., Gharahdaghi, F., Liu, X.F., Chopra, M., Ribadeneira, M., Marc, J., Chapdelaine, M.J., Dudley, A., Arriza, J.L., Maciag, C., Quirk, M.C. and Doherty, J.J. (2015) EEG-β/γ Spectral Power Elevation in Rat: A Translatable Biomarker Elicited by GABAAα2/3-Positive Allosteric Modulators at Nonsedating Anxiolytic Doses. Journal of Neurophysiology, 1, 116-131. http://dx.doi.org/10.1152/jn.00539.2013
Eye-Tracking
Psychophysiology
Spectral Power
EnkephaloVision
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Alonso, J.F., Romero, S., Ballester, M.R., Antonijoan, R.M. and Mananas, M.A. (2015) Stress Assessment Based on EEG Univariate Features and Functional Connectivity Measures. Physiological Measurement, 36, 1351-1365. http://dx.doi.org/10.1088/0967-3334/36/7/1351
Dimpfel, W. (2005) Pharmacological Modulation of Cholinergic Brain Activity and Its Reflection in Special EEG Frequency Ranges from Various Brain Areas in the Freely Moving Rat (Tele-Stereo-EEG). European Neuropsychopharmacology, 15, 673-682. http://dx.doi.org/10.1016/j.euroneuro.2005.03.006
Dimpfel, W. and Schober, F. (2001) Norepinephrine, EEG Theta Waves and Sedation. Brain Pharmacology, 1, 89-97.
Dimpfel, W. (2008) Pharmacological Modulation of Dopaminergic Brain Activity and Its Reflection in Spectral Frequencies of the Rat Electropharmacogram. Neuropsychobiology, 58, 178-186. http://dx.doi.org/10.1159/000191124
Dimpfel, W., Koch, K. and Weiss, G. (2011) Early Effect of NEURAPAS ® Balance on Current Source Density (CSD) of Human EEG. BMC Psychiatry, 11, 123-138. http://dx.doi.org/10.1186/1471-244X-11-123
Dimpfel, W., Koch, K. and Weiss, G. (2012) Single Dose Effects of PASCOFLAIR ® on Current Source Density (CSD) of Human EEG. Neuroscience & Medicine, 3, 130-140. http://dx.doi.org/10.4236/nm.2012.32018
Dimpfel, W. (2015) Drug Discovery and Translational Medicine Based on Neurophysiological Techniques Provide a Holistic Approach to Saving Animals. Books on Demand, Norderstedt.
Dimpfel, W., Chiegoua Dipah, G.N. and Gericke, N. (2016) Enkephalo Vision: Anatomical Functionality Indicated by Ultrashort Transient Regional EEG Spectral Power Changes during Cognitive and Emotional Challenges. World Journal of Neuroscience, 6, 90-10. http://dx.doi.org/10.4236/wjns.2016.62012
Dimpfel, W. (2014) Neurophysiological Effects of Rhodiola Rosea Extract Containing Capsules (A Double-Blind, Randomised, Placebo-Controlled Study). International Journal of Nutrition and Food Sciences, 3, 157-165.
Dimpfel, W. and Hofmann, H.C. (2014) Neurocode-Tracking Based on Quantitative Fast Dynamic EEG Recording in Combination with Eye-Tracking. World Journal of Neuroscience, 4, 106-119. http://dx.doi.org/10.4236/wjns.2014.42013
Dimpfel, W. (2011) Enkephaloglyphen: Spektrale Signaturen der elektrischen Gehirntätigkeit als Spiegel der Psyche. Books on Demand, Norderstedt.
Jasper, H.H. (1958) The Ten-Twenty Electrode System of the International Federation. Electroencephalography and Clinical Neurophysiology, 10, 371-375.
Dolce, G. and Waldeier, H. (1974) Spectral and Multivariate Analysis of EEG Changes during Mental Activity in Man. Electroencephalography and Clinical Neurophysiology, 36, 577-584. http://dx.doi.org/10.1016/0013-4694(74)90224-7
Mizuki, Y., Tanaka, M., Isozaki, H., Nishijima, H. and Inanaga, K. (1980) Periodic Appearance of Theta Rhythm in the Frontal Midline Area during Performance of a Mental Task. Electroencephalography and Clinical Neurophysiology, 49, 345-351. http://dx.doi.org/10.1016/0013-4694(80)90229-1
Schober, F., Schellenberg, R. and Dimpfel, W. (1995) Reflection of Mental Exercise in the Dynamic Quantitative Topographical EEG. Neurobiology, 31, 98-112.
Coenen, A.M.L. (1998) Neural Phenomena Associated with Vigilance and Consciousness: From Cellular Mechanisms to Electroencephalographic Pattern. Consciousness and Cognition, 7, 42-53. http://dx.doi.org/10.1006/ccog.1997.0324
Wyczesany, M., Kaiser, J. and Coenen, A.M.L. (2008) Subjective Mood Estimation Co-Varies with Spectral Power EEG Characteristics. Acta Neurobiologiae Experimentalis, 68, 180-192.
Corradini, P.L. and Persinger, M.A. (2015) Replace Psychometric Inferences with Direct Brain Measurements: LORETA Reflects Traditional Cerebral Loci for Neuropsychological Tests. Neuroscience & Medicine, 6, 107-115. http://dx.doi.org/10.4236/nm.2015.63018
Bastiaansen, M.C., Oostenfeld, R., Jensen, O. and Hagoort, P. (2008) I See What You Mean: Theta Power Increases Are Involved in the Retrieval of Lexical Semantic Information. Brain and Language, 106, 15-28. http://dx.doi.org/10.1016/j.bandl.2007.10.006
Raghavachari, S., Lisman, J.E., Tully, M., Madsen, J.R. and Bromfield, E.B. (2006) Theta Oscillations in Human Cortex during a Working Memory Task: Evidence for Local Generators. Journal of Neurophysiology, 95, 1630-1638. http://dx.doi.org/10.1152/jn.00409.2005
Crawford, H.J., Clarke, S.W. and Kitner-Triolo, M. (1996) Selfgenerated Happy and Sad Emotions in Low and Highly Hypnotizable Persons during Waking and Hypnosis: Laterality and Regional EEG Activity Differences. International Journal of Psychophysiology, 24, 239-266. http://dx.doi.org/10.1016/S0167-8760(96)00067-0
Filipovic, S.R., Covicovic-Sternic, N., Stojanovic-Svetel, M., Lecic, D. and Kostic, V.S. (1989) Depression in Parkinson Disease: An EEG Frequency Analysis Study. Parkinsonism & Related Disorders, 4, 171-178. http://dx.doi.org/10.1016/S1353-8020(98)00027-3
Klimesch, W., Doppelmayr, M., Pachinger, T. and Ripper, B. (1997) Brain Oscillations and Human Memory: EEG Correlates in the Upper Alpha and Theta Band. Neuroscience Letters, 238, 9-12. http://dx.doi.org/10.1016/S0304-3940(97)00771-4
Klimesch, W. (1999) EEG Alpha and Theta Oscillations Reflect Cognitive and Memory Performance: A Review and Analysis. Brain Research Reviews, 29, 169-195. http://dx.doi.org/10.1016/S0165-0173(98)00056-3
Zheng, L., Jiang, Z. and Yu, E. (2007) Alpha Spectral Power and Coherence in the Patients with Mild Cognitive Impairment during a Three-Level Working Memory Task. Journal of Zhejiang University Science, 8, 584-592. http://dx.doi.org/10.1631/jzus.2007.B0584