Brain and Behavior Issue 3.5 is Now Online

BRB 3 5The latest issue of Brain and Behavior looks at first language writing systems’ impact on second language word reading and examines the posterior insular cortex.  The cover features an image from, “Distinction between hand dominance and hand preference in primates: a behavioral investigation of manual dexterity in nonhuman primates (macaques) and human subjects” by Pauline Chatagny, Simon Badoud, Mélanie Kaeser, Anne-Dominique Gindrat, Julie Savidan, Michela Fregosi, Véronique Moret, Christine Roulin, Eric Schmidlin, and Eric M. Rouiller

Below is another article highlight, chosen by the editorial team. 

purple_lock_open The role of rs2237781 within GRM8 in eating behavior
By Marie-Therese Gast, Anke Tönjes, Maria Keller, Annette Horstmann, Nanette Steinle, Markus Scholz, Ines Müller, Arno Villringer, Michael Stumvoll, Peter Kovacs, and Yvonne Böttcher
Abstract: The glutamate receptor, metabotropic 8 gene (GRM8) encodes a G-protein-coupled glutamate receptor and has been associated with smoking behavior and liability to alcoholism implying a role in addiction vulnerability. Data from animal studies suggest that GRM8 may be involved in the regulation of the neuropeptide Y and melanocortin pathways and might influence food intake and metabolism. This study aimed to investigate the effects of the genetic variant rs2237781 within GRM8 on human eating behavior. 

Link to the full table on contents here.

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Brain and Behavior: Issue 3 Highlights and Introducing Altmetric!

BRB 3 3Brain and Behavior’s latest issue brings together research on increased risk of anxiety from cigarette smoking, the effects of bisphenol A on social behavior in mice, and how the brain responds to cognitive load.  The cover features an image from, Neuroanatomical and neuropharmacological approaches to postictal antinociception-related prosencephalic neurons: the role of muscarinic and nicotinic cholinergic receptors by Renato Leonardo de Freitas,  Luana Iacovelo Bolognesi, André Twardowschy, Fernando Morgan Aguiar Corrêa, Nicola R. Sibson, Norberto Cysne Coimbra.

We’re also excited to announce that Brain and Behavior is participating in a pilot program offered by the service Altmetric to offer authors and users alternative metrics for articles and datasets to measure their impact on both traditional and social media. 

Below is another highlight chosen by the editorial team. 

purple_lock_open Crucifixion and median neuropathy
By Jacqueline M. Regan, Kiarash Shahlaie, Joseph C. Watson
Abstract: Crucifixion as a means of torture and execution was first developed in the 6th century B.C. and remained popular for over 1000 years. Details of the practice, which claimed hundreds of thousands of lives, have intrigued scholars as historical records and archaeological findings from the era are limited. As a result, various aspects of crucifixion, including the type of crosses used, methods of securing victims to crosses, the length of time victims survived on the cross, and the exact mechanisms of death, remain topics of debate. One aspect of crucifixion not previously explored in detail is the characteristic hand posture often depicted in artistic renditions of crucifixion. In this posture, the hand is clenched in a peculiar and characteristic fashion: there is complete failure of flexion of the thumb and index finger with partial failure of flexion of the middle finger. Such a “crucified clench” is depicted across different cultures and from different eras. A review of crucifixion history and techniques, median nerve anatomy and function, and the historical artistic depiction of crucifixion was performed to support the hypothesis that the “crucified clench” results from proximal median neuropathy due to positioning on the cross, rather than from direct trauma of impalement of the hand or wrist.

Link to the full table of contents here.

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Article level metrics: Painting a fuller picture

AltmetricsArticle level metrics (ALMs) have become an important tool to establish a more complete picture of the impact of individual papers, distinct from the publication in which they appear.  While more traditional measurements – such as citations and usage – assess the scholarly visibility of a paper, alternative metrics are emerging to measure social visibility by tracking online conversations around scientific articles. [1]

As part of our continued commitment to providing content based services to users and authors, Wiley has launched a trial of ALMs on a number of journals. Partnering with Altmetric, we will be running a six month trial on both subscription and open access journals including Advanced Materials, Angewandte Chemie, BJUI, Brain and Behavior, Methods in Ecology and Evolution and EMBO Molecular Medicine.

 Altmetric tracks social media sites like Twitter, Facebook, Google+, Pinterest and blogs, newspapers, magazines and online reference managers like Mendeley and CiteULike for mentions of the scholarly articles published in the journals.

Altmetric creates and displays a score for each article measuring the quality and quantity of attention that the particular article has received. The Altmetric score is based on three main factors: the number of individuals mentioning a paper, where the mentions occurred (e.g. a newspaper, a tweet) and how often the author of each mention talks about the article.

 Alternative metrics, such as the ALMs provided by Altmetric, help calculate the immediate and specific impact of an individual article rather than just relying on traditional benchmarks such as the journal’s impact factor.  Wiley will be undertaking further pilots before rolling out enhanced metrics across more journals.

For authors, alternative metrics enables them to better understand the social impact of their individual paper in real time and for journal editors, alternative metrics can help to quantify the full extent of their publications’ visibility and reach.

Our journal publishes articles that are among the most highly accessed and cited in scientific research,” Dr. Peter Gregory, Editor in Chief, Advanced Materials explains. “We want to provide readers with access to our research through all channels, with authors enjoying a prominent social media presence and excellent coverage in the global news and science media. It will be interesting to review the Altmetric data as it becomes available to better quantify journal article impact.”

 1: Article-Level Metrics a SPARC Primer by Greg Tananbaum

Read Brain and Behavior’s latest issue highlights

BRB 3 2Check out these highlights from the latest issue of Brain and Behavior.

Issue 2 of Brain and Behavior features research on the impact of Gene Therapy on Parkinson’s disease, pain processing in patients with unresponsive wakefulness syndrome, and attention’s effect on neural activity in primary sensorimotor cortex  The cover features an image from, Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis by Caty Casas, Mireia Herrando-Grabulosa, Raquel Manzano, Renzo Mancuso, Rosario Osta, and  Xavier Navarro

Below are two more standout articles selected by the editorial team. 

purple_lock_open  Human hippocampal energy metabolism is impaired during cognitive activity in a lipid infusion model of insulin resistance
By Yaso Emmanuel, Lowri E. Cochlin, Damian J. Tyler, Celeste A. de Jager, A. David Smith, and Kieran Clarke

Abstract: Neuronal glucose uptake was thought to be independent of insulin, being facilitated by glucose transporters GLUT1 and GLUT3, which do not require insulin signaling. However, it is now known that components of the insulin-mediated glucose uptake pathway, including neuronal insulin synthesis and the insulin-dependent glucose transporter GLUT4, are present in brain tissue, particularly in the hippocampus. There is considerable recent evidence that insulin signaling is crucial to optimal hippocampal function. The physiological basis, however, is not clear. We propose that while noninsulin-dependent GLUT1 and GLUT3 transport is adequate for resting needs, the surge in energy use during sustained cognitive activity requires the additional induction of insulin-signaled GLUT4 transport. We studied hippocampal high-energy phosphate metabolism in eight healthy volunteers, using a lipid infusion protocol to inhibit insulin signaling. Contrary to conventional wisdom, it is now known that free fatty acids do cross the blood–brain barrier in significant amounts. Energy metabolism within the hippocampus was assessed during standardized cognitive activity. 31Phosphorus magnetic resonance spectroscopy was used to determine the phosphocreatine (PCr)-to-adenosine triphosphate (ATP) ratio. This ratio reflects cellular energy production in relation to concurrent cellular energy expenditure. With lipid infusion, the ratio was significantly reduced during cognitive activity (PCr/ATP 1.0 ± 0.4 compared with 1.4 ± 0.4 before infusion, P = 0.01). Without lipid infusion, there was no reduction in the ratio during cognitive activity (PCr/ATP 1.5 ± 0.3 compared with 1.4 ± 0.4, P = 0.57). This provides supporting evidence for a physiological role for insulin signaling in facilitating increased neuronal glucose uptake during sustained cognitive activity. Loss of this response, as may occur in type 2 diabetes, would lead to insufficient neuronal energy availability during cognitive activity.

purple_lock_open  Brain processing of pain in patients with unresponsive wakefulness syndrome
By Alexandra Mark,  Tao Yu, Dominik Vogel, Friedemann Müller, Boris Kotchoubey, and Simone Lang

Abstract: By definition, patients with unresponsive wakefulness syndrome (UWS) do not experience pain, but it is still not completely understood how far their brain can process noxious stimuli. The few positron emission tomography studies that have examined pain processing did not yield a clear and consistent result. We performed an functional magnetic resonance imaging scan in 30 UWS patients of nontraumatic etiology and 15 age- and sex-matched healthy control participants (HC). In a block design, noxious electrical stimuli were presented at the patients’ left index finger, alternating with a resting baseline condition. Sixteen of the UWS patients (53%) showed neural activation in at least one subsystem of the pain-processing network. More specifically, 15 UWS patients (50%) showed responses in the sensory-discriminative pain network, 30% in the affective pain network. The data indicate that some patients completely fulfilling the clinical UWS criteria have the neural substrates of noxious stimulation processing, which resemble that in control individuals. We therefore suppose that at least some of these patients can experience pain.

Link to the full table of contents here >

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Brain and Behavior’s first 2013 issue is now online!

BRB 3 1Brain and Behavior’s latest issue  offers compelling research on topics including sensory neuropathy, maternal depression and basilar atherosclerosis, among others.    The cover features an image from, Social exclusion, infant behavior, social isolation, and maternal expectations independently predict maternal depressive symptoms John Eastwood, Bin Jalaludin, Lynn Kemp, Hai Phung, Bryanne Barnett and Jacinta Tobin “Bi-plot of latent variables social exclusion, social isolation and infant behavior.”

Below are two more standout articles selected by the editorial team. 

purple_lock_open  Comparative study of environmental factors influencing motor task learning and memory retention in sighted and blind crayfish
By Sonya M. Bierbower,  Zhanna P. Shuranova, Kert Viele and Robin L. Cooper
Abstract: Schematic representation of the motor task conditioning chamber. The chamber is divided into two compartments, the larger one housing the animal and the smaller one containing a mesh platform with the food reward. Food was attached to the mesh screen. (A) A stylized angled view including the two compartments and mesh screen with worms attached. The location of the access point is indicated by the arrow. (B) Side view schematic to show placement of the mesh platform and the manipulative task of reaching in and up to obtain the food reward.

purple_lock_open  High-resolution MRI of basilar atherosclerosis: three-dimensional acquisition and FLAIR sequences
By Tanya N. Turan,  Zoran Rumboldt, Truman R. Brown
Abstract: This case report describes the use of high-resolution magnetic resonance imaging (HRMRI) to visualize basilar artery atherosclerotic plaque in a patient with a pontine stroke. HRMRI with three-dimensional image acquisition was used to visualize plaque in several planes to localize arterial wall pathology. Fluid attenuated inversion recovery (FLAIR) sequences of the basilar artery showed wall thickening throughout the basilar artery wall and good contrast between the artery wall and cerebrospinal fluid.

Link to the full table of contents here.

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Wiley signs Open Access Agreements with Helmholtz Association and University of Manitoba

Ten institutes of the Helmholtz Association and the University of Manitoba have signed up for Wiley Open Access Accounts.   These agreements provide active financial support and a streamlined process for authors to ensure open access to their published research in Wiley-Blackwell journals.  Authors affiliated with the Univesity of Manitoba and the institutes of the Helmholtz Association listed below can now benefit from these arrangements when publishing articles in Wiley Open Access journals.

Alfred-Wegener-Institut für Polar- und Meeresforschung
Deutsches Elektronen-Synchrotron DESY
Deutsches Krebsforschungszentrum
Deutsches Zentrum für Luft- und Raumfahrt
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Forschungszentrum Jülich
GEOMAR Helmholtz-Zentrum für Ozeanforschung Kiel
Helmholtz-Zentrum für Infektionsforschung
Helmholtz-Zentrum für Umweltforschung – UFZ
Karlsruher Institut für Technologie

The University of Manitoba and the Helmholtz Association insitutions join a number of funders who have opened a Wiley Open Access Account since this was launched. Browse our listing to see the institutions / funders who have an account or partnership with Wiley Open Access.

More information about our open access options for funders and institutions can be found here.

The Carrot and the Stick?

Unraveling Motivation and Attention

by Randolph S. Marshall, Career Corner Editor

A commentary on the recent Brain and Behavior article, “Effects of Motivation on Reward and Attentional Networks: an fMRI Study”, by Ivanov et al.

How does the anticipation of a reward interact with cognitive demand? This is the basic question that was asked by K-23 awardee IIllyan Ivanov. In his article just published in Brain and Behavior, Ivanov and colleagues used BOLD fMRI to examine regional brain activation in a 3-pronged experiment that pitted the motivational system against the attentional system. Both the motivation of an anticipated reward and higher levels of attention are known to speed up cognitive reaction times behaviorally, but what is the influence of the motivational system on cognitive control as a task requires more cognitive muscle? Does reward anticipation enhance performance or interfere with it?  What if there is not only promise of reward, but risk of monetary loss? These questions are important both for our understanding of systems biology, and for implications of treatment of individuals with attention deficit/hyperactivity disorder, obsessive-compulsive disorder, and drug addiction where attention and motivation may be altered.

In this study of 16 healthy adults, behavior results were as anticipated: shorter reaction times were seen with reward anticipation, particularly with the easier, “congruent” task trials. The imaging results confirmed that attentional network regions (right ACC, right primary motor cortex, supplemental motor and somatosensory association cortices bilaterally, right middle frontal gyrus and right thalamus) activated more during the higher cognitive demands of the non-congruent trials whereas key components of the motivational network (bilateral insula and ventral striatum) engaged with the unique “surprising non-reward” component of the task. Furthermore, the interaction effects showed that cognitive conflict elicited greater activation, but only in the absence of reward incentives – as if subjects worked harder to avoid possible loss. Conversely, reward anticipation decreased activity in the attentional networks possibly due to improved information processing.

Surprisingly, the more difficult task components decreased activity in the striatum and the orbito-frontal cortex suggesting that harder trails may have been experienced as less rewarding. These results were interpreted as showing that in the context of a difficult task one can maximize performance through both increasing efforts to obtain rewards on easier trials and committing more attentional effort to avoid punishment and losses during more difficult trials. The authors conclude that there is not a direct correlation between motivational incentives and improvement of performance, but that their interplay will highly depend on the context.

I interviewed Dr. Ivanov about his experiment, and asked him to talk about the process of beginning his career in clinical neuroscience. Dr. Ivanov is currently Assistant Professor in Child Psychiatry at Mt. Sinai Medical Center in New York. He completed a K-23/R02 sponsored by grant in 2010, sponsored by NIDA/AACAP and now is completing his work on an R03 to study the effects of motivation and attention in more depth.

Marshall:  What was the most interesting finding for you in this study?

Ivanov: The interaction effect, which suggested that incentives may boost information processing but can also be a distractor and possibly hamper performance on cognitive tasks. This is interesting because new studies suggest that if you have strong stimuli (e.g. a drug like methylphenidate) this interaction effect may be reversed as we hope to show in a follow up study.

Marshall: Was clinical relevance an important motivator for you in pursuing this project, or were you more interested in the systems biology aspect?

Ivanov: I would say both. As a clinician I was interested in the main idea which was whether we could tap into risk factors that would help us understand the motivational and attentional systems. I wanted to know if there is a biological signature or hallmark for what treatment might be helpful in children at risk for later substance abuse.

Marshall: How important was mentorship in the design and implementation of this work?

Ivanov: Crucial, especially with neuroimaging.  The amount of time and the amount of knowledge needed was very high.  I had both inside and outside mentors. I studied with the Director of Child Psychiatry at Mt. Sinai, Jeffrey Newcorn, and with outside mentors also, which turned out to be a very good thing. I worked with Tom Crowley, an adult psychiatrist at Denver, and Edith London from UCLA, who was a mentor for my K-23.  I also went to the Wellcome Trust Centre for Neuroimaging in London a couple of times to work with Karl Friston. Through this process what you find is that you accumulate a group of people around the country or the world who you can then count on later for advice and support.

Marshall: What was the hardest part about getting this project done?

Ivanov: I didn’t know much about neuroimaging when I started. I was naïve about the time needed to complete a neuroimaging study in young children. It’s not like clinical work, in which we get used to working quickly.  Getting used to working in that scientific environment is different.  It is also very demanding moving humans into human research, particularly youths. You have to work with kids and family through the whole process.  Children have their natural curiosity, but entering the fMRI scanner is not an everyday experience and they can be fearful – having a skilled research team is crucial.

Marshall: What is the next hypothesis to test? Is it a direct follow up of this project or will you work on a parallel project?

Ivanov: We may be able to set up a treatment trial. We want to ask, do you see clinical   subgroups with particular biological signatures that might optimize our treatments for high risk groups.

Marshall: What advice would you give a young investigator looking to get a first K-award or similar grant funded?

Ivanov: Get a good mentor. A good mentor will help flesh out your ideas.  Also, you have to find an area you are really interested in and feel really passionate about.  And when you start thinking about the process, don’t have the goal right away of producing the paper that will turn science around.  Concentrate on learning, increasing your background knowledge, and developing your network. The best outcome for the K is to develop the confidence and skills that will let you succeed in the future.

The Evolution of Author Guidelines

Congratulations are due to PeerJ for succeeding in bringing into focus an essential publisher service that has been little publicised in the past.

The journal opened for submissions on December 3rd, and many tweets and blogs have been spawned by the following passage in the Instructions for Authors:

We want authors spending their time doing science, not formatting.

We include reference formatting as a guide to make it easier for editors, reviewers, and PrePrint readers, but will not strictly enforce the specific formatting rules as long as the full citation is clear.

Styles will be normalized by us if your manuscript is accepted.

Of course, it would be ridiculous to assert that every manuscript ever submitted up to this point had perfectly formatted references in journal style; in fact it is relatively rare to make no edits at all on a reference list. Journal Production Editors have been converting reference formats since journal publishing began; laboriously at first, but the digital revolution has certainly helped in recent years, with more automated processes and specialist typesetters taking on much of the tedium.

 As the PeerJ guidelines correctly state, a requirement for a particular style can help the editorial and review process, and I would go further in saying that it can impose some rigour on the creation of the reference list, helping to ensure that all critical elements are present. However, it has been the case for some time that publishers have barely batted an eye if an article happens to arrive in the incorrect format, as long as all of the important content was present.

 At Wiley, we took this a stage further on the launch of our Wiley Open Access program back in May 2011. We made a point of paring the formatting requirements down to a bare minimum for the entire article. The Author Guidelines state:

 We place very few restrictions on the way in which you prepare your article, and it is not necessary to try to replicate the layout of the journal in your submission. We ask only that you consider your reviewers by supplying your manuscript in a clear, generic and readable layout, and ensure that all relevant sections are included. Our production process will take care of all aspects of formatting and style.

And with respect to the references:

 As with the main body of text, the completeness and content of your reference list is more important than the format chosen. A clear and consistent, generic style will assist the accuracy of our production processes and produce the highest quality published work, but it is not necessary to try to replicate the journal’s own style, which is applied during the production process. If you use bibliographic software to generate your reference list, select a standard output style, and check that it produces full and comprehensive reference listings…The final journal output will use the ‘Harvard’ style of reference citation. If your manuscript has already been prepared using the ‘Vancouver’ system, we are quite happy to receive it in this form. We will perform the conversion from one system to the other during the production process.

There is no doubt that this service, which has been quietly in operation in most journals for some time, has now been thrown much more into the limelight, and this can only be positive because it showcases one of the valuable services that professional publishing can provide.

Reading through the blogs, I see that the more overt adoption of this service as a point of policy is already spreading to more journals, as it has to eLife, and Elsevier’s Free Radical Biology & Medicine.

 This can only be a good thing.

Will Wilcox, Journals Content Management Director for Life Sciences

Issue 2.6 of Brain and Behavior is now freely available online!

BRB 2 6 coverThe latest issue of Brain and Behavior is now live!  The journal publishes research articles across all areas of neurology, neuroscience, psychology and psychiatry. The cover features an image from Isolated CNS Whipple disease with normal brain MRI and false-positive CSF 14-3-3 protein: a case report and review of the literature by Victor W. Sung, Michael J. Lyerly, Kenneth B. Fallon and Khurram Bashir: “Brain tissue showing the bacteria responsible for causing CNS Whipple disease, Tropheryma whipplei, present both within macrophages (right) and free in the neuropil (left).” We have 13 excellent papers in this issues, all of which are fully open access.

Below are two top articles highlighted by our editorial team:

purple_lock_open Cellular basis for singing motor pattern generation in the field cricket (Gryllus bimaculatus DeGeer)  by Stefan Schöneich and Berthold Hedwig.
Abstract: The singing behavior of male crickets allows analyzing a central pattern generator (CPG) that was shaped by sexual selection for reliable production of species-specific communication signals. After localizing the essential ganglia for singing in Gryllus bimaculatus, we now studied the calling song CPG at the cellular level. Fictive singing was initiated by pharmacological brain stimulation. The motor pattern underlying syllables and chirps was recorded as alternating spike bursts of wing-opener and wing-closer motoneurons in a truncated wing nerve; it precisely reflected the natural calling song.

purple_lock_open BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control in healthy humans byRuud Smolders, Mark Rijpkema, Barbara Franke and Guillén Fernández.
Abstract: Brain-derived neurotrophic factor (BDNF) plays a critical role in brain development. A common single nucleotide polymorphism in the gene encoding BDNF (rs6265, Val66Met) affects BDNF release and has been associated with altered learning and memory performance, and with structural changes in brain morphology and corpus callosum integrity. BDNF Val66Met has more recently been shown to influence motor learning and performance. Some of the BDNF effects seem to be modulated by an individual’s sex, but currently the relationship between BDNF and sex in the motor domain remains elusive. Here, we investigate the relationship between BDNF Val66Met genotype and an individual’s sex in the motor system.

Read out other top articles in this issue >

Submit your article to Brain and Behavior via the online submission site >
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Additional Editor-in-Chief for Brain and Behavior

Maryann MartoneWe are delighted to announce that Maryann Martone is joining us as a co-Editor-in-Chief of Brain and Behavior. Dr. Martone is a neuroscientist at the University of California at San Diego and a leader in the field of neuroinformatics, and she will complement the expertise Andrei Alexandrov brings to the journal as a practicing neurologist.

Dr. Martone started at UCSD in 1993 in the Department of Neurosciences and is currently the co-director of the National Center for Microscopy and Imaging Research as well as the principal investigator of the Neuroscience Information Framework project. She has also served as the US scientific representative to the International Neuroinformatics Coordinating Facility (INCF), helping to develop tools and standards for neuroscience data exchange. We are excited to have a Maryann join our team, as her breadth of knowledge and experience make her uniquely qualified to work on an open access journal, such as Brain and Behavior, with the goals of rapid and wide dissemination of research in neuroscience, neurology, psychology, and psychiatry.

You can submit your paper to Brain and Behavior here >

Brain and Behavior’s latest issue is now live!

BRB 2 5 coverBrain and Behavior has now published the fifth issue of 2012. The journal publishes research articles across all areas of neurology, neuroscience, psychology and psychiatry. Below are two top papers which our editorial team have highlighted. The cover image of this issue is taken from the first of these papers.

Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain by Agnieszka Krzyzanowska and Carlos Avendaño
Abstract: This comprehensive review of the currently used rodent models of orofacial inflammatory and neuropathic pain examines the available testing methods and procedures used for assessing the behavioral responses in the face in both mice and rats. It also provides a summary of some pharmacological agents used in these paradigms and the use of these agents in animal models is also compared with outcomes observed in the clinic.

Prescription stimulants in individuals with and without attention deficit hyperactivity disorder: misuse, cognitive impact, and adverse effects by Shaheen E. Lakhan and Annette Kirchgessner
Abstract: Prescription stimulants are often used to treat attention deficit hyperactivity disorder (ADHD). Drugs like methylphenidate (Ritalin, Concerta), dextroamphetamine (Dexedrine), and dextroamphetamine-amphetamine (Adderall) help people with ADHD feel more focused. However, misuse of stimulants by ADHD and nonaffected individuals has dramatically increased over recent years based on students’ misconceptions or simple lack of knowledge of associated risks. Given the widespread belief that stimulants enhance performance, there are in fact only a few studies reporting the cognitive enhancing effects of stimulants in ADHD and nonaffected individuals. Moreover, these drugs are associated with dangers including myocardial infarction, cardiomyopathy, and even sudden death.

You can submit your article to Brain and Behavior via the online submission site. Reasons to submit:
• High standard, rigorous peer review
• Rapid publication
• Open Access – published articles are licensed under the  Creative Commons Atrribution License and authors are the copyright holder
• Compliant with open access mandates
• Indexed in PubMed
• Promotion and publicity of quality research
• Wiley’s tradition in publishing excellence

Bringing the Bench to the Bedside

Exploring underlying mechanisms of cranial electrotherapy stimulation

by Randolph S. Marshall, Career Corner Editor

A commentary on the recent Brain and Behavior article, “Effects of crainal electrotherapy stimulation on resting state brain activity”, by Feusner et. al.

This interesting article by Dr. Feusner (K23 recipient) and colleagues addresses a perennial problem in neuroscience – how to verify the scientific validity of an empirically proven therapy. Feusner et. al. set out to explain the underlying mechanism of cranial electrotherapy stimulation (CES), a long-standing empirical treatment for mood alteration which received FDA approval in 1979. CES has been used for a variety of indications including anxiety, insomnia, depression, and pain, but without clear physiological explanation of its effect. Although several studies have reported beneficial results, it has remained unclear how subsensory alternating current delivered to the earlobes at .5 or 100Hz can alter behavioral symptoms. Preclinical work had shown effects of CES on slowing of alpha waves on EEG in monkeys, associated with reduced adverse reactions to stressful stimuli, but it was unclear whether changes in brain waves were a cause or an effect of improved clinical states. Given uncertainty about mechanisms, the authors proposed to look at effects of CES on brain activity by delivering CES to healthy control subjects while in an fMRI scanner.

One of the strengths of this study, and a general principle for successful investigations of this kind, was the generation of plausible a priori hypotheses based on other studies. Clear statement of hypotheses such as the following establish the scientific context of the study, and let the reader know what to look for in interpreting the results. The hypotheses were:

  1. CES would cause a general deactivation in cortical and thalamic regions because of prior evidence that the stimulation reduces alpha power on EEG.
  2. CES would produce alteration in connectivity networks such as default mode network (DMN) because CES 100Hz affects the EEG beta band, which correlates most highly with the DMN.
  3. CES would alter other connectivity networks such as the dorsal fronto-parietal network (FPN) because there was clinical evidence of CES affect on attention, and the sensorimotor network (SMN) because of clinical evidence for CES effect on pain.

Although there was no randomization, the study design was to use baseline (“off”) periods compared to “on” periods during stimulation. Subject blinding was done by forced choice testing prior to scanning to ensure that participants couldn’t tell if the CES machine was on or off. Subjects had no knowledge of status while in the scanner, and thus there would be no behavior confounder for changes in BOLD fMRI activity.

The authors found that CES correlated with a decreased activation in several brain regions – bilateral SMA, right supramarginal gyrus, right superior parietal and left superior frontal. No increases in regional brain activation were found. The connectivity results demonstrated that the 100Hz stimulation altered the DMN. The FPN and SMN showed no change with CES, and only the higher frequency stimulation produced alterations in connectivity.

Based on these results, the authors concluded that the study demonstrated positive proof that there is a biological effect of CES. The electrical current was proposed to reach the cortex where it would disrupt brain oscillation patterns. The reduction in BOLD activity in several brain regions was consistent with previous EEG studies demonstrating reduction in alpha frequency signal. The altered connectivity for 100 Hz and not .5 Hz was consistent with knowledge that 100Hz frequency affects the beta band, which correlates with DMN activity.  The authors closed the discussion with several unanswered questions, including how the CES alteration of brain activation and connectivity translates to clinical effect, and whether the fMRI BOLD effects they observed would be similar in subjects who had a depression, anxiety, insomnia, or pain.


This was an excellent study from the perspective of initiating a line of inquiry. Aside from the results themselves helping to advance our understanding of the effects of external electrical stimulation on brain activity, this is a strategic line of inquiry from a career perspective. Studies such as these are both hypothesis-testing and hypothesis-generating. What better way to justify your next study or grant than to generate an interesting question by answering the one at hand? High-level neuroscience journals are rife with this type of investigation. In addition, from a grants perspective, early phase clinical trial proposals are now expected to include a physiological “surrogate marker” of efficacy. Developing an imaging method to assess underlying mechanisms of clinical phenomena can therefore be a fruitful line of investigation. Congratulations to Dr. Feusner et al, and good luck with your next study!

Questions for discussion:

  1. Did the results as reported in the paper have ecological validity, i.e. seem plausible, interesting, and relevant to clinical practice? What additional studies would need to be done to convince you that the results are valid? Which hypotheses were left unproven and why?
  2. What weaknesses can be identified in the study design? What are the strengths/advantages of this design?
  3. What is the next hypothesis to test? How would the next study be best designed?

Please visit the Brain and Behavior homepage for more high-quality, Open Access papers and to sign up for our new content alerts!

Wiley Moves towards Broader Open Access Licence

John Wiley & Sons, Inc., today announced revised licensing arrangements for proprietary journals published under the Wiley Open Access program. The journals will adopt the Creative Commons Attribution (CC-BY) license which allows commercial use of published articles.

The Wiley Open Access portfolio also includes journals published with society partners, many of which will similarly transfer to the Creative Commons Attribution license.

Wiley is responding to recent developments in funder and government policies and supports the sustainable evolution of scientific publishing. The change will be implemented immediately.

Rachel Burley Vice President and Director, Open Access commented “Wiley is committed to meeting the evolving needs of the authors who wish to provide open access to the published articles that convey the results of their research.”  

Burley continued “Our announcement today concerns Wiley’s fully open access journals. We are also reviewing the licensing arrangements for our hybrid program OnlineOpen, our open access option for individual articles published in subscription journals. In consultation with our publishing partners, we aim to continue to develop and deliver sustainable open access products providing author choice and high levels of service.”

In the first instance, the journals moving to the CC-BY license are Brain and Behavior, Ecology and Evolution, MicrobiologyOpen, Cancer Medicine, Food Science & Nutrition, Evolutionary Applications, Geoscience Data Journal and EMBO Molecular Medicine.

The CC-BY license allows (with the correct attribution of the original creator) for the copying, distribution and transmission of the work. Adaption and commercial use is also permitted.   

More information about Wiley’s open access initiatives is available online.