The Effectiveness of Neurofeedback and Stimulant Drugs in Treating AD/HD: Part II. Replication

This study replicated T. R. Rossiter and T. J. La Vaque (1995) with a larger sample, expanded age range, and improved statistical analysis. Thirty-one AD/HD patients who chose stimulant drug (MED) treatment were matched with 31 patients who chose a neurofeedback (EEG) treatment program. EEG patients received either office (n = 14) or home (n = 17) neurofeedback. Stimulants for MED patients were titrated using the Test of Variables of Attention (TOVA). EEG (effect size [ES] = 1.01–1.71) and MED (ES = 0.80–1.80) groups showed statistically and clinically significant improvement on TOVA measures of attention, impulse control, processing speed, and variability in attention. The EEG group demonstrated statistically and clinically significant improvement on behavioral measures (Behavior Assessment System for Children, ES = 1.16–1.78, and Brown Attention Deficit Disorder Scales, ES = 1.59). TOVA gain scores for the EEG and MED groups were not significantly different. More importantly, confidence interval and nonequivalence null hypothesis testing confirmed that the neurofeedback program produced patient outcomes equivalent to those obtained with stimulant drugs. An effectiveness research design places some limitations on the conclusions that can be drawn.     

Ethical Research Issues: Going Beyond the Declaration of Helsinki

La Vaque and Rossiter made a strong, supported argument that it is unethical to use a no treatment control group in a research study if a known, effective treatment is available. Their argument is based on the supposition that the Declaration of Helsinki is the ethical world standard for research with humans. Their argument appears to be straightforward, but is not simple to apply. The issues are very complex, include issues not discussed in their argument, and can lead to a different conclusion as pointed out in this paper. The World Medical Association developed the Declaration of Helsinki as one of their official policies. The Declaration of Helsinki, however, is not accepted as the world ethical standard, as demonstrated by its lack of adoption by many professional associations or even by the United States Federal Government. Perhaps it is not mentioned because its ethical provisions are aspirational rather than mandatory as implied by La Vaque and Rossiter. Researchers and clinicians should also be aware of other ethical issues not directly discussed in the La Vaque and Rossiter paper. The Belmont Report is the basis for the ethical protection of human research subjects for at least 17 federal agencies and does not mention the Declaration of Helsinki. The Belmont Report mentions several ethical principles that form the basis for informed consent, risk/benefit assessment, confidentiality of data, subject selection, Institutional Review Boards, and other protections needed when doing research with human subjects. At least 2 of these core principles have direct implications to the discussion related to the use of placebo controls. The ethical principle of fidelity is also important in guiding research activities with human subjects. Researchers should be familiar with the La Vaque and Rossiter argument, the Belmont Report, and the federal policies developed to implement the provisions of that report, for example, Regulation 45 CFR 46.     

A Comment on La Vaque and Rossiter

The paper by La Vaque and Rossiter recommends that placebo-controlled trials only be conducted when best proven treatments are not available. In this comment, I review evidence suggesting that identifying best proven treatments is a complex task involving many variables and that making such a decision entails many real-world difficulties.     

Evaluation of the effectiveness of EEG neurofeedback training for ADHD in a clinical setting as measured by changes in T.O.V.A. scores,behavioral ratings,and WISC-R performance

A study with three component parts was performed to assess the effectiveness of neurofeedback treatment for Attention Deficit/Hyperactivity Disorder (ADHD). The subject pool consisted of 23 children and adolescents ranging in age from 8 to 19 years with a mean of 11.4 years who participated in a 2-to 3-month summer program of intensive neurofeedback training. Feedback was contingent on the production of 16–20 hertz (beta) activity in the absence of 4–8 hertz (theta) activity. Posttraining changes in EEG activity, T.O.V.A. performance, (ADDES) behavior ratings, and WISC-R performance were assessed. Part I indicated that subjects who successfully decreased theta activity showed significant improvement in T.O.V.A. performance; Part II revealed significant improvement in parent ratings following neurofeedback training; and Part III indicated significant increases in WISC-R scores following neurofeedback training. This study is significant in that it examines the effects of neurofeedback training on both objective and subjective measures under relatively controlled conditions. Our findings corroborate and extend previous research, indicating that neurofeedback training can be an appropriate and efficacious treatment for children with ADHD.The first author (Joel F. Lubar) has provided consultative services for both Lexicor and Stoelting-Autogenics Corporations in order to help them develop appropriate protocols for neurofeedback. He is not an owner, stockholder, or employee for either organization.     

Reviews

Book Reviewed in this article: Goodenough, J., McGuire, B. & Wallace, R. 1993: Perspectives on animal behavior. John Wiley & Sons Inc. Jarman, P. J. & Rossiter, A. (eds) 1994: Animal societies. Individuals, interactions and organisation. Lever, Ch. 1994: Naturalized animals: the ecology of successfully introduced species. Poyser-Verlag, London. Canadian Museum of Nature - Musée Canadien de la nature 1991: The secret world of animals. 1: Below and above the ground. 2: Under the water. 3: In the air. 4: On the earth. 5: Le monde secret des animaux.     

Measuring the effectiveness of a mass customization and personalization strategy: a market- and organizational-capability-based index

The research of Kumar (Int J Flex Manuf Syst 16(4):287–312, 2004) is expanded to develop a methodology that measures the effectiveness of a mass customization and personalization strategy using a mass customization and personalization effectiveness index. This index extends Kumar (2004) in three significant ways: (1) it encompasses both service and manufacturing companies, (2) the assessment of product customization considers that customers assign different weights to different product features, and (3) the index captures the impact of both market perception and system capabilities. Three different measures are proposed. Which is appropriate should be a function of a particular company’s parameters. The circumstances under which each measure is best is a subject for future research. The validation and reliability of this index and these measures are also issues that should be addressed by future research.     

Commentary on two misconceptions of phylogeny and classification

A recent brief communication criticizes a morphometric study of the structure of Daubentonia (Oxnard, 1981). The criticisms are invalid because they apply to the concept of the detailed character state in a localized anatomical region, a type of morphological information different than the broad measurement that embodies many characters. The criticisms themselves display, moreover, exactly those problems of prior assumption that the underlying philosophy of multivariate morphometric studies as used by Oxnard (1981) tries to eliminate.     

Reviews

Book reviewed in this article: Møller , A. P. 1994: Sexual selection and the barn swallow. Wehner, R., Lehrer, M. & Harvey , W. R. (eds) 1996: Navigation, migration, and homing. Maclean , G. L. 1996: Ecophysiology of desert birds. Keulen, C., Loneux, M., Poncin, P. & Ruwet , J.-Cl. 1994: La Biodiversité: une étude de cas — ‘le site de Lanaye’ en Meuse belgo-néerlandaise. Gansloßer, U., Hodges, J. K. & Kaumanns , W. (eds) 1995: Research and captive propagation. Henry , J. D. 1996: Red fox. The catlike canine.     

Book Reviews

Craig, John F. & Kemper, J. Bryan (Eds) Regulated Streams, Advances in Ecology.
Askew, R.R. (1988) The Dragonflies of Europe.
Holdich, D.M. & Lowery, R.S. (Eds) (1988) Freshwater Crayfish, Biology, Management and Exploitation.
McDowall, R.M. (1988) Diadromy in Fishes: Migrations between Freshwater and Marine Environments.
Muir, J.E. & Roberts, R.J. (Eds) (1988) Recent Advances in Aquaculture , Vol. 3.
Dejoux, Claude (1988) La pollution des eaux continentales africaines. Experience acquise, situation actuelle et perspectives.
Burgis, M.J. & Symoens, J.J. (Eds) (1987) African Wetlands and Shallow Water Bodies: Directory ORSTOM , Paris.
Swanson, G.A., Winter, T.C., Adomaitis, V.A. & La Baugh, J.W. (1988) Chemical Characteristics of Prairie Lakes in Southcentral North Dakota - this Potential for Influencing use by Fish and Wildlife.
Drummond Sedgwick, S. (1988) Salmon Farming Handbook.     

Foundation and Practice of Neurofeedback for the Treatment of Epilepsy

This review provides an updated overview of the neurophysiological rationale, basic and clinical research literature, and current methods of practice pertaining to clinical neurofeedback. It is based on documented findings, rational theory, and the research and clinical experience of the authors. While considering general issues of physiology, learning principles, and methodology, it focuses on the treatment of epilepsy with sensorimotor rhythm (SMR) training, arguably the best established clinical application of EEG operant conditioning. The basic research literature provides ample data to support a very detailed model of the neural generation of SMR, as well as the most likely candidate mechanism underlying its efficacy in clinical treatment. Further, while more controlled clinical trials would be desirable, a respectable literature supports the clinical utility of this alternative treatment for epilepsy. However, the skilled practice of clinical neurofeedback requires a solid understanding of the neurophysiology underlying EEG oscillation, operant learning principles and mechanisms, as well as an in-depth appreciation of the ins and outs of the various hardware/software equipment options open to the practitioner. It is suggested that the best clinical practice includes the systematic mapping of quantitative multi-electrode EEG measures against a normative database before and after treatment to guide the choice of treatment strategy and document progress towards EEG normalization. We conclude that the research literature reviewed in this article justifies the assertion that neurofeedback treatment of epilepsy/seizure disorders constitutes a well-founded and viable alternative to anticonvulsant pharmacotherapy.     

Timing of omitted events: an analysis of temporal control of inhibitory behavior

This paper reviews research designed to investigate the temporal control of inhibitory responding using rats as subjects. One area of investigation has focused on the role of temporal variables in conditioned inhibition produced using Pavlov's [Pavlov, I.P., 1927. Conditioned Reflexes. Oxford University Press, London, 430 pp.] procedure. These studies have found that evidence of conditioned inhibition obtained by negative summation testing is strongest when the conditioned inhibitor signals the omission of the unconditioned stimulus (US) at the same temporal location as a transfer excitor signals presentation of the US [e.g., Barnet, R.C., Miller, R.R., 1996. Temporal encoding as a determinant of inhibitory control. Learn. Motiv. 27, 73-91]. Similarly, retardation of acquisition of behavioral control by a previously inhibitory conditioned stimulus (CS) is maximal when the inhibitory CS is paired with the US at the same temporal location as the inhibitor had previously signaled US omission [Burger, D., Denniston, J.C., Miller, R.R., 2001. Temporal coding in condition inhibition: retardation tests. Anim. Learn. Behav. 29, 281-290]. Other lines of research designed to assess the associative structure of temporal control of inhibition [e.g., Denniston, J.C., Blaisdell, A.P., Miller, R.R., 2004. Temporal control in conditioned inhibition: analysis of associative structure of inhibition. J. Exp. Psychol. Anim. Behav. Process. 30, 190-202] are reviewed, as is the assessment of temporal control of inhibition produced through extinction [Denniston, J.C., Miller, R.R., 2003. The role of temporal variables in inhibition produced through extinction. Learn. Behav. 31, 35-48]. These collective observations are discussed in terms of the temporal coding hypothesis [Matzel, L.D., Held, F.P., Miller, R.R., 1988. Reexamination of simultaneous and backward conditioning: Implications for contiguity theory. Learn. Motiv. 19, 317-344].     

Exopolysaccharide production by Acremonium diospyri in continuous culture

Production of an exopolysaccharide (glucan) by Acremonium diospyri was not markedly affected by its specific growth rate, the culture pH or the stirrer speed under NH ₄ ⁺ -limiting chemostat conditions. The exopolysaccharide was also detected in the medium under conditions of NH ₄ ⁺ excess.P. Wood and R.J. Seviour are with the Biotechnology Research Centre, La Trobe University College of Northern Victoria, Bendigo, Victoria 3550, Australia     

Neurofeedback Training for Opiate Addiction: Improvement of Mental Health and Craving

Psychological improvements in patients with substance use disorders have been reported after neurofeedback treatment. However, neurofeedback has not been commonly accepted as a treatment for substance dependence. This study was carried out to examine the effectiveness of this therapeutic method for opiate dependence disorder. The specific aim was to investigate whether treatment leads to any changes in mental health and substance craving. In this experimental study with a pre-post test design, 20 opiate dependent patients undergoing Methadone or Buprenorphine maintenance treatment were examined and matched and randomized into two groups. While both experimental and control groups received their usual maintenance treatment, the experimental group received 30 sessions of neurofeedback treatment in addition. The neurofeedback treatment consisted of sensory motor rhythm training on Cz, followed by an alpha-theta protocol on Pz. Data from the general health questionnaire and a heroin craving questionnaire were collected before and after treatment. Multivariate analysis of covariance showed that the experimental group achieved improvement in somatic symptoms, depression, and total score in general mental health; and in anticipation of positive outcome, desire to use opioid, and relief from withdrawal of craving in comparison with the control group. The study supports the effectiveness of neurofeedback training as a therapeutic method in opiate dependence disorder, in supplement to pharmacotherapy.     

Task Force Report on methodology and empirically supported treatments: introduction

Recent criticism of biofeedback has increased the importance of rating the efficacy of each biofeedback and neurofeedback therapy. A joint task force of the Association for Applied Psychophysiology and Biofeedback (AAPB) and the Society for Neuronal Regulation (SNR) has developed standards for efficacy research methodology and template for rating the level of efficacy of each application. The Task Force Report has been approved as a policy guideline by both the AAPB and SNR Boards.     

Experimental tests of trophic dynamics: towards a more penetrating approach

The complex interactions between primary producers, herbivores, carnivores, and detritivores have resulted in the burgeoning field of trophic dynamics. One important contribution is the Fretwell and Oksanen theory (FO theory). The FO theory proposes that the productivity of the environment determines the length of the trophic chain, which, they suggest, is directly related to whether the system is being controlled by top-down forces (odd numbered length of trophic chain) or bottom-up forces (even numbered length of trophic chain). Recent evidence from experiments by L.H. Fraser and J.P. Grime claims to support the FO theory but the methodology has been criticised by D.C. Moon, P. Stiling and M.V. Cattell for hidden treatments and pseudoreplication. We reject these criticisms and recommend an approach to the study of trophic dynamics involving the aggregation of organisms into functional groups, direct quantitative measurements of trophic processes using field manipulations, inferences based upon the use of field probes and synthesis of ecosystems in closed microcosms. Received: 15 December 1998 / Accepted: 10 December 1998     

A Pilot Study of Neurofeedback for Chronic PTSD

EEG Biofeedback (also known as neurofeedback) has been in use as a clinical intervention for well over 30 years; however, it has made very little impact on clinical care. One reason for this has been the difficulty in designing research to measure clinical change in the real world. While substantial evidence exists for its efficacy in treating attention deficit/hyperactivity disorder, relatively little evidence exists for its utility in other disorders including posttraumatic stress disorder (PTSD). The current study represents a “proof-of-concept” pilot for the use of neurofeedback with multiply-traumatized individuals with treatment-resistant PTSD. Participants completed 40 sessions of neurofeedback training two times per week with sensors randomly assigned (by the study coordinator, who was not blind to condition) to sensor placements of either T4-P4 or T3-T4. We found that neurofeedback significantly reduced PTSD symptoms (Davidson Trauma Scale scores averaged 69.14 at baseline to 49.26 at termination), and preceded gains in affect regulation (Inventory of Altered Self-Capacities-Affect Dysregulation scores averaged 23.63 at baseline to 17.20 at termination). We discuss a roadmap for future research.     

The Effects of QEEG-Informed Neurofeedback in ADHD: An Open-Label Pilot Study

In ADHD several EEG biomarkers have been described before, with relevance to treatment outcome to stimulant medication. This pilot-study aimed at personalizing neurofeedback treatment to these specific sub-groups to investigate if such an approach leads to improved clinical outcomes. Furthermore, pre- and post-treatment EEG and ERP changes were investigated in a sub-group to study the neurophysiological effects of neurofeedback. Twenty-one patients with ADHD were treated with QEEG-informed neurofeedback and post-treatment effects on inattention (ATT), hyperactivity/impulsivity (HI) and comorbid depressive symptoms were investigated. There was a significant improvement for both ATT, HI and comorbid depressive complaints after QEEG-informed neurofeedback. The effect size for ATT was 1.78 and for HI was 1.22. Furthermore, anterior individual alpha peak frequency (iAPF) demonstrated a strong relation to improvement on comorbid depressive complaints. Pre- and post-treatment effects for the SMR neurofeedback sub-group exhibited increased N200 and P300 amplitudes and decreased SMR EEG power post-treatment. This pilot study is the first study demonstrating that it is possible to select neurofeedback protocols based on individual EEG biomarkers and suggests this results in improved treatment outcome specifically for ATT, however these results should be replicated in further controlled studies. A slow anterior iAPF at baseline predicts poor treatment response on comorbid depressive complaints in line with studies in depression. The effects of SMR neurofeedback resulted in specific ERP and EEG changes.     

Can Neurofeedback Training Enhance Performance? An Evaluation of the Evidence with Implications for Future Research

There have been many claims regarding the possibilities of performance enhancement training. The aim of such training is for an individual to complete a specific function or task with fewer errors and greater efficiency, resulting in a more positive outcome. The present review examined evidence from neurofeedback training studies to enhance performance in a particular area. Previous research has documented associations between specific cortical states and optimum levels of performance in a range of tasks. This information provides a plausible rationale for the use of neurofeedback to train individuals to enhance their performance. An examination of the literature revealed that neurofeedback training has been utilised to enhance performance from three main areas; sport, cognitive and artistic performance. The review examined evidence from neurofeedback training studies within each of these three areas. Some suggestive findings have been reported with regard to the use of neurofeedback training to enhance performance. However, due to a range of methodological limitations and a general failure to elicit unambiguous changes in baseline EEG activity, a clear association between neurofeedback training and enhanced performance has yet to be established. Throughout, the review highlights a number of recommendations to aid and stimulate future research.     

Physiological levels of PTEN control the size of the cellular Ins(1,3,4,5,6)P(5) pool

To understand how a signaling molecule's activities are regulated, we need insight into the processes controlling the dynamic balance between its synthesis and degradation. For the Ins(1,3,4,5,6)P5 signal, this information is woefully inadequate. For example, the only known cytosolic enzyme with the capacity to degrade Ins(1,3,4,5,6)P5 is the tumour-suppressor PTEN [J.J. Caffrey, T. Darden, M.R. Wenk, S.B. Shears, FEBS Lett. 499 (2001) 6 ], but the biological relevance has been questioned by others [E.A. Orchiston, D. Bennett, N.R. Leslie, R.G. Clarke, L. Winward, C.P. Downes, S.T. Safrany, J. Biol. Chem. 279 (2004) 1116 ]. The current study emphasizes the role of physiological levels of PTEN in Ins(1,3,4,5,6)P5 homeostasis. We employed two cell models. First, we used a human U87MG glioblastoma PTEN-null cell line that hosts an ecdysone-inducible PTEN expression system. Second, the human H1299 bronchial cell line, in which PTEN is hypomorphic due to promoter methylation, has been stably transfected with physiologically relevant levels of PTEN. In both models, a novel consequence of PTEN expression was to increase Ins(1,3,4,5,6)P5 pool size by 30-40% (p<0.01); this response was wortmannin-insensitive and, therefore, independent of the PtdIns 3-kinase pathway. In U87MG cells, induction of the G129R catalytically inactive PTEN mutant did not affect Ins(1,3,4,5,6)P(5) levels. PTEN induction did not alter the expression of enzymes participating in Ins(1,3,4,5,6)P5 synthesis. Another effect of PTEN expression in U87MG cells was to decrease InsP6 levels by 13% (p<0.02). The InsP6-phosphatase, MIPP, may be responsible for the latter effect; we show that recombinant human MIPP dephosphorylates InsP6 to D/L-Ins(1,2,4,5,6)P5, levels of which increased 60% (p<0.05) following PTEN expression in U87MG cells. Overall, our data add higher inositol phosphates to the list of important cellular regulators [Y. Huang, R.P. Wernyj, D.D. Norton, P. Precht, M.C. Seminario, R.L. Wange, Oncogene, 24 (2005) 3819 ] the levels of which are modulated by expression of the highly pleiotropic PTEN protein.