Can Sugar be Addicting?

by Michael Kuhar, PhD



Editor’s Note:

Dr. Kuhar is a Candler Professor at the Yerkes National Primate Research Center and Senior Faculty Fellow in the Center for Ethics at Emory University.  An expert in addiction, he is one of the most productive and highly cited scientists worldwide.  He has received a number of prestigious awards for his work, and is involved in many aspects of brain/behavioral research and education.



You might be interested in his book: The Addicted Brain. 





Recently, Constance Harrell facilitated an Emory Neuroethics Program Neuroscience and Neuroethics in the News Seminar on sugar and depression. Obesity became a topic and, not surprisingly, out of this discussion arose the question, “Can sugar be addicting?”  This is closely related to the question, “Can food be addicting?”



Somebody might say, we need sugar/food to be healthy, and we can’t do without them, so how can we say they are addicting?  Well, there is an answer to this.  Addiction, by definition, is seeking and taking a substance even though there are negative consequences.  Negative consequences are key. So if we take a substance but there are no negative consequences, addiction wouldn’t be in the discussion.  The question of danger for addiction and abuse might be, but definite addiction probably wouldn’t be (Kuhar 2012).



Consider taking opiates for pain.  Chronic pain patients repeatedly take morphine or similar medicines for a long time.  These patients are “dependent” because if they stop the drug, they go into painful withdrawal. But they are not “addicted” because they don’t compulsively seek out the drug and experience negative consequences.  This would be different from the addict who searches for heroin and in doing so breaks the law, ignores relationships, health, and work, etc.  So you can “need” something but yet not exhibit the key identifier of addiction, which is seeking and taking even though they are destructive.  We can need food, but yet not experience it as destructive, provided it is taken in moderate quantities and provides necessary nutrients. But perhaps some do experience the negative. As with drugs, there are interpersonal variations in how we experience sugar.  An extreme case would be a person with diabetes where taking sugar is more dangerous.



Also, the effects of drugs (and presumably sugary foods) will depend on the dose or amount taken.  High doses of drugs can have effects that low doses do not.  So having high doses of sugary foods can have effects in the body that low doses do not really produce. So sugar is not always sugar.  The dose or quantity that you consume, and how often you consume it, can have unique effects that you won’t necessarily experience at lower doses and frequencies. Such dose-response relationships are well known and well-studied in pharmacology and research (Kuhar 2012).



Drug abuse studies show that most people can walk away from drugs like heroin, but some don’t (maybe 1-13 % by some estimates depending on the substance) and become or are addicts. Translating that to sugar, only a small percentage of sugar “users” would be “addicted.”



What is the official position on sugar and food as addicting?  At this point in time, many feel that there are not enough peer reviewed studies that show food is addicting (DSM-5, 2013).  The studies just haven’t been done yet.  Some suspect that once the research has been conducted, sugar and food will fit the criteria for being addicting in some people.  We will see.



There is some evidence that is compatible with sugar being addicting (Schreiber et al 2013; Hone-Blanchet and Fectaeu, 2014; Ahmed et al 2013;Kenny et al 2013; Hadad and Knackstedt 2014; Tau and Potenza 2013). Some people eat sugary foods in ways and quantities that are not healthy, and therefore they have negative consequences.  Obesity is on everyone’s mind. Eating sugary foods regularly can also result in craving and a loss of control, hallmarks of addictive behavior.  Sugar can make you feel good, just like addicting drugs can. Sugar can be taken in binges, just like drugs. Stress can precipitate both drug taking and eating. Some research even suggests that sugar can be more rewarding than cocaine (Lenoir et al 2007). Brain scans of dopamine receptors in obese subjects are similar to those from drug addicts (Kenny et al 2013). And more can be said. At this point in time, many feel that sugary foods can be addicting in some, and that this eventually will be proven in rigorous ways.



What makes a sugar/food addict?  Well, again extrapolating from findings in drug abuse and addiction, there could be several factors that increase our vulnerability for addiction.  We don’t know enough to say for sure when and how a specific person will be an addict.  We can only consider large populations of addicts and look at how they are and how they behave.  The main vulnerability conferring factors include genetics, environmental factors including personal support, conditioning, and stress.  Also, there are protective factors such as a very supportive environment (Kuhar 2012).



What do we do if we are in trouble?  Get counseling.  Pay attention to risk factors and work to counteract them. In drug addiction, the more time spent in rehab gives a better outcome by staying away from drugs.  It takes work and a significant time commitment, and many people have been and will continue to be helped.



Selected Readings



Ahmed SH, Guillem K, Vandaele Y. Sugar addiction: pushing the drug-sugar analogy to the limit. Curr Opin Clin Nutr Metab Care. 2013 Jul;16(4):434-9. doi: 10.1097/MCO.0b013e328361c8b8.



DSM-5. American Psychiatric Association.  2013. P 481. “ …groups of repetitive behaviors, which some term behavioral addictions, with such subcategories  as sex addiction (and presumably food addiction)… are not included because at this time there is insufficient peer reviewed evidence…to identify these behaviors as mental disorders.”



Hadad NA, Knackstedt LA. Addicted to palatable foods: comparing the neurobiology of Bulimia Nervosa to that of drug addiction. Psychopharmacology (Berl). 2014 May;231(9):1897-912. doi:10.1007/s00213-014-3461-1.



Hone-Blanchet A, Fecteau S. Overlap of food addiction and substance use disorders definitions: analysis of animal and human studies. Neuropharmacology. 2014 Oct;85:81-90. doi:10.1016/j.neuropharm.2014.05.019. Epub 2014 May 24.



Kenny PJ, Voren G, Johnson PM. Dopamine D2 receptors and striatopallidal transmission in addiction and obesity. Curr Opin Neurobiol. 2013 Aug;23(4):535-8.



Kuhar, MJ.  The Addicted Brain.  FT press. Upper Saddle River, NJ. 2012.



Lenoir M, Serre F, Lauriane L, and Ahmed SH. Intense Sweetness Surpasses Cocaine Reward. PLoS ONE. 2007; 2(8): e698. Published online 2007 Aug 1. doi:10.1371/journal.pone.0000698.



Yau YH, Potenza MN. Stress and eating behaviors. Minerva Endocrinol. 2013 Sep;38(3):255-67.



Want to cite this post?



Kuhar, M. (2015). Can Sugar be Addicting? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2015/04/can-sugar-be-addicting.html

Burden of proof: does neuroscience have the upper hand?

As an undergraduate, I took several introductory level philosophy classes while
majoring in neuroscience. Some of it I could appreciate and most of it went
over my head, but a thought that kept nagging me was, “haven’t neuroscientists
solved all of these issues by now?” It was only after I had worked in
neuroscience laboratories for a few years that I began to realize just how
qualified all of our statements had to be due to the plethora of limitations that
go along with any result. I began to wince anytime I heard someone use the word
“proof” (only salesmen use the term “clinically proven”, but don’t get me
started on that…). It seems clear to me now that, for the most part, natural
scientists, social scientists and humanities scholars are really all working
toward the same goal just in different, albeit complimentary ways. At the first
“Neuroscience, ethics and the news” journal club of the semester, Lindsey
Grubbs, a PhD student in Emory University’s English Department, facilitated our
discussion about a topic that she has previously written about for this site.
The main focus was on what role neuroscience can and should play in answering
questions that have long been in the realm of the humanities and how these
results should be communicated to the general public.

From the Daily Mail Online

At the center of
our discussion were two papers about the effects of reading that each created
quite a stir
in the popular press. First, Gregory Berns’
laboratory at Emory reported on a study that they had conducted which was aimed
at determining how a good book can leave such a lasting impression (1).  They reasoned, “It seems plausible that if
something as simple as a book can leave the impression that one’s life has been
changed, then perhaps it is powerful enough to cause changes in brain function
and structure.” Berns and colleagues asked undergraduates to read a novel over
the course of nine days and had them come into the lab for a short
resting-state functional Magnetic Resonance Imaging (fMRI) scan each morning
during that time. They utilized an internal control model where each
participant was also scanned prior to reading and after finishing the novel.




Dr. Berns and his
colleagues found significant short-term changes in activity levels in areas
that had previously been associated with “story comprehension” and “perspective
taking” – the “left angular/supramarginal gyri and right posterior temporal
gyri” – and somewhat persistent changes in somatosensory cortical connectivity.
They interpreted the latter results as a possible substrate for the phenomenon
of “embodied semantics,” where the brain’s somatosensory processing machinery
can be recruited by just the thought of performing an action or experiencing a
sensation (2).
Importantly, nowhere in the paper do the authors put a valuation on these
changes as “good” or “bad” yet headlines such as “Brain
function improves for DAYS after reading a novel” appeared. Increased
connectivity between discrete brain regions does not necessarily mean that
brain function is improved. Is this simply a result of a positive bias in favor
of reading? If the same neurological changes were found in chronic drug abusers,
I doubt they would be interpreted as improvements.

From ScienceDaily

The second study (3),
published in Science by Kidd and
Castano (2013), took a very different approach and also received a great deal
of attention (positive,
negative,
and borderline
ridiculous). Here, the researchers from The New School
set out to determine if literary fiction – defined as award-winning and/or
canonical rather than best-selling – alters measures of Theory of Mind, the ability to
infer and understand the mental states of others. To do this, they put subjects
through a battery of tests aimed at measuring affective and cognitive Theory of
Mind after reading either literary or popular fiction or nothing at all. Kidd
and Castano conclude their article by arguing that their results highlight the
importance of reading literature in contrast to the controversial US Common Core standards which de-emphasize
reading fiction in secondary education. Slate’s Mark Liberman has written at length
about the shortcomings
of this study’s design and its perhaps over-reaching interpretations. His piece
was titled “That study on literary fiction and empathy proves exactly nothing”
– I couldn’t agree more (but I could say that about any paper). Liberman’s
somewhat aggressive title may have been in response to Zach Schonfeld’s “Now
we have proof that reading literary fiction makes you a better person” (shudder).




Hyperbole aside,
there are two issues here that deserve attention. First, do we really need neuroscientific evidence in order
to promote reading, and in particular, reading great, canonical works? Even
hardcore, card-carrying reductionists would likely agree that a lack of
biological evidence for the benefit of reading does not necessarily mean it
isn’t good for you. The risk is that the public comes away from these articles
thinking that now that neuroscientists have weighed in, the debate is over.
Also of note, Kidd and Castano never use the word “brain” (or “neuron”,
“neural”, etc.) because this is a psychology study, aimed at understanding the
effects of reading on how the mind
works. Neuroscientists could certainly look for neural correlates for the
psychological changes exerted specifically by literary fiction on the brain but
even if they were not able to find anything that would not mean that the
changes aren’t real. An underlying issue here, outlined by Lindsey and
discussed by the group, is that natural science results – and in particular
those from neuroscience – are highly persuasive to the public (4, 5).
Here, the media largely reported that these studies proved the benefits of
reading, which hardly seems like a controversial topic. However, Common Core
standards are quite controversial
and the amount and type of reading (i.e. fiction vs. non-fiction) are hotly
contested topics. While neuroscientists and psychologists certainly could
weigh in here, there is a concern that their results may be more influential
than perhaps they should be.

From alanrinzler.com

Second, a problem
that arose with several of these popular press articles is the attachment of a
value judgment to the changes that scientists reported. As mentioned above, it
is likely that the reason that words like “improvement” were added to describe
these neural changes is because reading is already seen as a positive
influence. Internet pornography addicts probably would have had a similar change
– if it existed – labeled as a “pathological rewiring.” Perhaps this is a
remnant of the brain being thought of as a muscle that needs to be exercised.
In that analogy, any increase does seem like an improvement but that obviously
is not always the case (for example, uncontrolled excitatory activity can lead
to seizures).




In reality, most
of the things we do and see and feel can probably change our brains in some
way, for better or worse – but whether or not neuroscientists alone are able to
find these changes doesn’t actually prove
anything.





References

1.         Berns GS, Blaine K, Prietula MJ, &
Pye BE (2013) Short- and long-term effects of a novel on connectivity in the
brain. Brain connectivity
3(6):590-600.

2.         Aziz-Zadeh
L & Damasio A (2008) Embodied semantics for actions: findings from
functional brain imaging. Journal of
physiology, Paris 102(1-3):35-39.

3.         Kidd
DC & Castano E (2013) Reading literary fiction improves theory of mind. Science 342(6156):377-380.

4.         Caulfield
TR, C. Zarzeczny, A (2010) “Neurohype” and the Name Game: Who's to Blame? AJOB Neuroscience 1(2):13-15.

5.         Weisberg
DS, Keil FC, Goodstein J, Rawson E, & Gray JR (2008) The seductive allure
of neuroscience explanations. Journal of
cognitive neuroscience 20(3):470-477.

Want to cite this post?




Purcell, R. (2014). Burden of proof: does neuroscience have the upper hand? The Neuroethics Blog. Retrieved on , from
http://www.theneuroethicsblog.com/2014/10/burden-of-proof-does-neuroscience-have.html

Stress Rx: Chant two Ommsss, with food, twice daily

How can and should meditation be used to restore physical and mental health in a clinical setting?  That is the question that Emory University neuroscience graduate student Jordan Kohn posed to begin the latest Neuroethics Journal Club.  The discussion thereafter centered on Black et al.’s 2013 Psychoneuroendocrinology paper entitled “Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial.”¹ This paper laudably attempts to bridge the mind-body gap and suggests a biological, and perhaps more importantly, a genetic mechanism to explain how yoga can apparently help relieve stress, protect against depression, and restore immune function in caregivers.  The implications of this line of investigation could be widespread as the scientific and medical communities grapple with our fundamental understanding of the mind and body and how to integrate what used to be considered fringe or alternative approaches into the mainstream.



Caregivers for dementia patients have been widely studied because they experience high levels of chronic stress and in turn suffer high rates of depression and other mental and physical health problems.² Both acute and chronic stress can drastically alter immune system function³ and, not surprisingly, dementia patient caregivers show marked impairments in immunological measures.⁴ The connection between the immune system and mental health is increasingly studied for its apparent bi-directionality.  Sickness behavior – characterized by fatigue, poor sleep, irritability, and lack of appetite – closely resembles major depression.  In fact, pro-inflammatory cytokines, which are up-regulated during an infection, can induce depression.⁴





In this study, participants were randomly assigned to practice the Kirtan Kriya Meditation, guided by an audio CD, for only 12 minutes per day, or to listen to a CD of relaxing music for the same amount of time each day.  After 8 weeks, nearly two thirds of the meditators had improved depression scale scores of at least 50% and most of them also scored 50% better than they had at baseline on a cognitive test.  Significantly fewer music listeners improved by 50% in either of these measures. These data had actually been, in part, reported previously⁶ but in this study the authors sought to determine whether meditation modulated gene expression in an attempt to understand how yogic meditation mechanistically elicits these beneficial effects.  Black and colleagues assessed genome-wide expression levels at baseline and post-treatment for both groups and also performed more focused analyses on genes related to immune system function or under the control of the well-known transcription factors NF-κB and IRF-1.⁹  They found that there was a significant reduction in the expression of genes that respond to NF- κB and an increase in those that can be activated by IRF-1 which, together would suggest a decrease in pro-inflammatory cytokines and a better functioning immune system.



This paper, along with a growing literature on the clinical benefits of meditation, raises the question of how ecologically valid such studies are and how one would, on a practical level, implement such interventions.  For one thing there is the issue of standardization.  Several high-profile meta-analyses have been performed to try to answer the question of whether meditative interventions actually improve clinical measures but only a fraction of relevant studies can be included in any one analysis due, at least in part, to the heterogeneity of interventions and study designs.^7,8 This has led to poor power which has made it difficult to determine what effect these interventions actually have.⁹ A second question is in what contexts should meditation be most appropriately prescribed? Our journal club facilitator, Jordan Kohn, noted that meditation has been shown to be useful for people incarcerated in prison and perhaps uniquely beneficial for training the military to cultivate their ‘Warrior Minds’ (though there may be additional ethical concerns for some). However, there may not be a one-size-fits all approach to meditation. While there might be benefit for stress reduction in Alzheimer’s caregivers, or cultivating compassion in those who are incarcerated, or creating sharper minds for our military personnel, Jordan mentioned that there may be some individuals who would not find benefit and might actually be harmed, by certain kinds of meditation. For example, individuals who suffered PTSD might only relive their trauma more vividly during their meditation sessions.



An important issue that this paper speaks to indirectly is the apparent necessity to have biological data to support psychological findings.  This is undoubtedly an important pursuit as it may lead to new therapeutic targets, but it also seems to be missing the point.  Does a psychological or mind-based intervention absolutely need to affect biological measures (in the body) in order to be valid?  In this case, the reported effect is most likely indirect where meditation helps to relieve perceptions of stress which may allow hormone levels to normalize and the immune system to get back to business as usual.  Since the authors do not report effects on any of the biological “levels” between the mind and gene transcripts in immune tissue, their genetics results serve mainly to support the aforementioned psychological data but do not really extend the findings.  However, in the public one can easily find alternative medicine skeptics as well as enthusiasts who are already mesmerized by the exoticism of meditative traditions and alternative medicine. Having a biological marker as compelling as genetic data might convince skeptics that meditation has true validity and is worthy of future funding and integration into clinical care.



Another question along these lines is whether biological measures – which can be altered by meditation – can shift a sense of disease responsibility?  It is well known that not every individual who is exposed to trauma or put under stress will develop a stress-related pathology.  Some people seem to be resilient.  If the remedy for those who are not resilient is a drug that alters neurochemistry, then one would think that the susceptibility must have been due to a pre-existing chemical imbalance – a biological deficit so to speak.  But if the prescribed therapy is to train yourself in mindfulness, then does that mean the disease is the result of a character or personality flaw?  That is, if a patient can just use his/her mind to reduce stress through meditation should the patient just summon the moral fortitude to not be so affected by stress to begin with?  One wonders if prescribing something like a pill versus meditation, indicates that the patient needs “real” medicine for their illness because it is something out of the patient’s control.  These and other issues are likely to be continually discussed as alternative approaches including meditation are increasingly studied and expanded into clinical settings.





References



1.  Black, D. S. et al. Yogic meditation reverses NF-kappa B and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology 38, 348-355, doi:DOI 10.1016/j.psyneuen.2012.06.011 (2013).

2.  Pinquart, M. & Sorensen, S. Differences between caregivers and noncaregivers in psychological health and physical health: A meta-analysis. Psychol Aging 18, 250-267, doi:Doi 10.1037/0882-7974.18.2.250 (2003).

3.  Dhabhar, F. S. & McEwen, B. S. Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: A potential role for leukocyte trafficking. Brain Behav Immun 11, 286-306, doi:DOI 10.1006/brbi.1997.0508 (1997).

4.  Lovell, B. & Wetherell, M. A. The cost of caregiving: Endocrine and immune implications in elderly and non elderly caregivers. Neurosci Biobehav Rev 35, 1342-1352, doi:DOI 10.1016/j.neubiorev.2011.02.007 (2011).

5.  Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W. & Kelley, K. W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nature reviews. Neuroscience 9, 46-56, doi:10.1038/nrn2297 (2008).

6.  Lavretsky, H. et al. A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity. International journal of geriatric psychiatry 28, 57-65, doi:10.1002/gps.3790 (2013).

7.  Goyal, M. et al. Meditation programs for psychological stress and well-being: a systematic review and meta-analysis. JAMA internal medicine 174, 357-368, doi:10.1001/jamainternmed.2013.13018 (2014).

8.  Grossman, P., Niemann, L., Schmidt, S. & Walach, H. Mindfulness-based stress reduction and health benefits. A meta-analysis. Journal of psychosomatic research 57, 35-43, doi:10.1016/S0022-3999(03)00573-7 (2004).

9.  Bartlett, T. "Wait, So Does Meditation Actually Work or Not?" in Percolator  (Chronicle.com, 2014).

10.  NF-κB and IRF-1 are transcription factors which, when activated by an extracellular signal, can induce the expression of a variety proteins in order to mount a cellular response. NF-κB is typically associated with an increase in pro-inflammatory cytokines whereas IRF-1 induces interferon beta, an antiviral cytokine.







Want to cite this post?



Purcell, R. (2014). Stress Rx: Chant two Ommsss, with food, twice daily. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/04/stress-rx-chant-two-ommsss-with-food.html

Can free will be modulated through electrical stimulation?

The will to persevere when many of life’s challenges are thrown at us is an ability that comes more naturally for some than for others. Additionally, even the most determined among us have days and times when moving forward through a challenging task just proves too difficult. The subjective nature of this experience can make it difficult to study, but recently researchers from Stanford University published a case study where electrical brain stimulation (EBS) to the anterior midcingulate cortex (aMCC) left two patients with the feeling that a challenge was approaching, but also that they could overcome it [1]. For the most recent journal club of the semester, Neuroscience graduate student and AJOB Neuroscience editorial intern Ryan Purcell led a discussion on the experimental procedure to stimulate what is referred to as the “the will to persevere” and the effect this technology may have if it were to become more mainstream in society.

"The location of the electrodes in P1 and P2 overlaid onto the standard emotional salience network derived from a group of normal human subjects." Parvizi et al.

It has long been known that the anterior cingulate cortex (ACC) and its midcingulate region (aMCC) are involved in emotions that rely on cognitive control, and recent research has shown that this brain network is possibly involved in complex emotions such as motivation and endurance [2,3]. In the case study discussed during journal club though, researchers went beyond an animal study and recorded a first-hand account of two patients becoming determined and motivated to overcome what they perceived as an oncoming challenge during EBS to the aMCC. The aMCC, located deep within the brain, is not typically implanted with electrodes for clinical reasons, but researchers were attempting to discover the origin of seizure activity in two patients with epilepsy by implanting intracranial electrodes in four different deep brain regions. Electrical currents at each of these regions were delivered and then based on patient feedback and physiological reports, researchers could localize the epileptic activity. It was determined that the patients were suffering from medial temporal epilepsy, but when electrical stimulation occurred at the aMCC, while no signs of seizures were observed, both patients did report similar and unique emotional states, along with specific physical symptoms. Patients physically experienced what was described as “shakiness,” hot flashes, and an increase in heart rate, but interestingly also psychologically felt a sense of foreboding regarding a challenge and the confidence that the challenge could be overcome. As seen in this supplemental video, patient 1 describes the experience as driving “towards a storm that’s on the other side, maybe a couple of miles away, and you've got to get across that hill.” Although this seems like a situation that would cause worry and anxiety, the same patient reported that the feeling was not really negative, but instead “it was more of a positive thing like…push harder, push harder, push harder to try and get through this.” These patient accounts suggest that researchers had tapped into the part of the brain responsible for motivation, endurance, and the will to persevere, and in doing so were able to elicit these feelings on command - far removed from any situation similar to stressful driving.



Researchers also realized that by stimulating the aMCC, the behavioral and emotional changes caused by EBS could potentially be due to functional changes that take place within a vast neuronal network connected to the aMCC. Using fMRI and functional connectivity analysis, researchers observed that EBS in the aMCC region of interest led to the activation of a network previously characterized as the emotional salience or cingulo-opercular network [4]. This suggests that the motivation, endurance, or the lack of these two emotions are most likely not alone regulated by a single brain region, the aMCC, but instead a complex, distributed network.



This paper presents the exciting and interesting idea that we could regulate motivation with stimulation to the brain, but really this is just a small case study with two patients. These findings may have been an unexpected result from trying to find the source of epilepsy, and may only occur in this experimental setting, perhaps even only in patients who have a history of epilepsy. The paper reads as if the researcher asking the questions of the patients was the same researcher conducting the stimulation trials, and as a result many of the questions are very biased and leading. After patient 1 has vividly compared his experience to driving in a storm, the researcher attempts to ask patient 2 about driving as well. To which patient 2 responds with laughter “I don’t get to drive.”



This is an interesting observation, but would need to be replicated on a larger scale with blind research practices put into place. However, since the aMCC is located deep within the brain and typically electrodes are not inserted for clinical reasons, it may prove difficult to conduct invasive procedures without a clinical agenda. In this case study, these patients were already unique in that they may have been very determined individuals even without external stimulation since they were undergoing invasive brain surgery for epilepsy most likely as a last resort. Having the power to increase motivation and/or determination could be used in a clinical setting for depression or chronic pain, and while it is only speculation regarding the personality traits of these two patients, a study that is open to participants without any diagnosed neurological disorders could provide more baseline activity for modulating the aMCC and its neuronal network. For this large study to take place though and to find interested participants, most likely the technology would need to advance with a noninvasive procedure.



While this type of technology would have obvious clinical benefits for treating depression and perhaps one day the ability to self-regulate our motivations at home, having the power to externally regulate free will begs certain questions. Should anyone be denied the chance to become a more productive, motivated version of themselves? Or, if this type of technology were considered acceptable, should anyone be forced to become a more determined, motivated citizen who does not experience weakness of will? If advances in neuroscience continue to address the questions of whether free will even exists at all, and then if we ever have the power to impose a standard of willpower that everyone should meet, this would have important implications for our legal and justice system. Two common theories for justifying punishment include the utilitarianism and the retributivism theory [5]. Simply put, utilitarianism is based on the idea that punishment is justified because it produces a situation in which the balance of good and evil (or happiness and unhappiness) is maximized [6]. Punishment helps to reduce crimes, which promotes a society where good prevails over evil. For example, punishment in the form of imprisonment can lead to the reduction of crime because the idea of prison can deter criminals and criminals are removed from society. The retributivism theory relies more on the idea of a social consensus on what is deemed a moral wrongdoing and criminals who commit crimes deserve to be punished [7]. If we had the power to control weakness of will and modulate willpower, this could be very powerful when applied to crimes that are associated with a weakness of will, perhaps those that involve illicit drugs, alcohol, or even the more heinous pedophilia, as specifically discussed in this previous blog post. However, then the justification of additional punishment according to the utilitarian viewpoint would be less valid, since the stimulation alone would potentially reduce crime. In this situation, a criminal would be giving up some level of free will in the name of societal benefits, so one could argue that electrical stimulation could be considered similar to jail time, a punishment that removes freedom and the ability to make many choices from perpetrators’ lifestyles. In this sense, additional punishment according to the retributivism theory would also be less valid since the electrical stimulation would be punishment enough. Finally, there is an additional possibility that is being explored by neuroscientists like David Eagleman who believe that our retributivist justice system (resulting in an overcrowded prison system) should be revised to one focused on rehabilitation, or rather neuro-rehabilitation [8, 9, 10]. Even in the name of rehabilitation though, does such a crime exist that justifies the punishment of nonconsensual direct manipulation of neuronal networks? Having the strength and the will to persevere is most likely a characteristic that we all want all the time, but is choosing not to persevere still a choice that we are always entitled to make, regardless of the context of the choice?





References:



1) Parvizi, J. et al. (2013). The Will to Persevere Induced by Electrical Stimulation of the Human Cingulate Gyrus. Neuron 80, 1359.

2) Rudebeck, P.E. et al. (2006). Separate neural pathways process different decision costs. Nat. Neurosci. 9, 1161.

3) Shackman, A.J. et al. (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nat. Rev. Neurosci. 12, 154.

4) Seeley, W.W. et al. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 27, 2349.

5) Greene, J.; Cohen, J. (2004). For the law, neuroscience changes nothing and everything. Phil. Trans. R. Soc. Lond. B 359, 1775.

6) Bernstein, R.F. (1979). Legal Utilitarianism. Ethics 89, 127.

7) Scheid, D.E. (1983). Kant's Retributivism. Ethics 93, 262.

8) Eagleman, D.The Brain on Trial. (2011). The Atlantic. Retrieved on April 7, 2014 from http://www.theatlantic.com/magazine/archive/2011/07/the-brain-on-trial/308520/.

9) A novel addiction therapy: The real-time fMRI. Initiative on Neuroscience and Law. Retrieved on April 7, 2014 from http://www.neulaw.org/research/real-time-fmri. 

10) Rommelfanger, K. (2011). Neuro-rehabilitation: A vision for a new justice system. The Neuroethics Blog. Retrieved on April 7, 2014, fromhttp://www.theneuroethicsblog.com/2011/10/neuro-rehabilitation-vision-for-new.html



Want to cite this post?



Strong, K. (2014). Can free will be modulated through electrical stimulation? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/04/can-free-will-be-modulated-through_8.html

Lamarckian sh*t? Why epigenetics is not eugenics

An argument could be made that communicating scientific advances to the public has never been more important. As the NIH budget stagnated, and then was cut by Sequestration, many of us have realized what a poor job we have been doing convincing the public of the importance of basic science research. Neuroscience itself has been under more scrutiny recently. As Adam Gopnik of The New Yorker wrote in a review of three new books bashing brain research, “Neuroscience can often answer the obvious questions but rarely the interesting ones.” If that is the way that the public sees it, then clearly we are losing something in translation. Recently there has been a push to reverse this trend and reaffirm biomedical research as a source of inspiration and hope for the public. The actor and author Alan Alda, who has long held a passion for science, has made it a personal mission to improve communication about science because “How are scientists going to get money from policy makers, if our leaders and legislators can’t understand what they do?”¹

Late last year, Brian Dias, a postdoctoral fellow in Kerry Ressler’s laboratory at Emory, found out just how difficult communicating his work to the public can be. Dias and Ressler had been working on testing whether olfactory fear conditioning would transmit a sensitivity to the conditioned odor across generations. That is, using a mouse model they were exploring whether an experience in your lifetime could affect your children or grandchildren’s response to their environment. They studied the olfactory system because it is extraordinarily well-mapped (thanks in large part to work that Dr. Ressler did in Nobel Laureate Linda Buck’s lab as a graduate student) and shows gross structural changes in mice when they learn to associate an odor with an unpleasant experience¹. Recently, there has been a great deal of interest in understanding how an organism’s environment can affect the way in which genes are expressed via a phenomenon call epigenetics.



Epigenetics refers to chemical modifications to the genome that do not affect the DNA sequence itself. Normally, the DNA molecule of each chromosome is tightly packed in a highly complex yet orderly fashion so that it can fit inside the nucleus of the cell. Several types of chemical modifications can be made to DNA that affect how tightly it packs and in turn, the ability of enzymes to transcribe the sequence and initiate the production of the proteins that it codes for. Epigenetic marks do not affect the letters in the code, just how often it is read. Genes can effectively be silenced or activated by these mechanisms, which are still not completely understood.



Researchers have found that the early life environment can have long term effects on individuals and even their offspring² – so called inter-generational epigenetics³. Lately, interest has even shifted to assessing trans-generational epigenetic effects. In 2010, an Australian group reported that in rodents, paternal high-fat diet can lead to dysfunction in pancreatic insulin-producing β-cells in female offspring⁴. More recently, a study of pre-diabetic mice found that epigenetic marks in the pancreas and, importantly, in sperm persisted for multiple generations as did a pre-disposition to impaired glucose metabolism⁵. Trans-generational epigenetic inheritance has been reported to affect lifespan in the nematode C. elegans⁶, and now some studies suggest that the effects of stress or abuse can be passed to the next generation in mice⁷ and humans⁸.



In this special Neuroethics Journal Club focused on “Neuroscience in the News”, the group was fortunate to get to hear the story of publishing this exciting paper⁹ first hand from Dr. Dias. One of the most interesting aspects of the discussion was the timing of the initial presentation of the results and publication of the paper. Dias gave a presentation at Neuroscience 2013 on November 12^th that created a great deal of buzz, so much so that Virginia Hughes of National Geographic’s “Only Human” blog reported on the presentation and also on the Twitter activity itself. Reponses ranged from “Astonishing if true” to “Crazy Lamarkian [sic] shit”.



The Nature Neuroscience editors themselves may have been thinking something along the same lines as the latter commenter as they made a portrait of Jean-Baptiste Lamarck – the champion of the contentious evolutionary theory that acquired adaptations during life shape subsequent generations – the cover image for the issue with Dias and Ressler’s article. The trouble with associating Lamarck and trans-generational epigenetics is that it could lead to the same type of reasoning that gave rise to eugenics in the early to mid-20^th century. Disadvantaged individuals who have lived with hunger and been exposed to violence or other trauma could be seen as permanently damaged and may be dissuaded from having children to avoid perpetuating some sort of “bad epigenetics”. The fact is, genes simply code for proteins and the jump from the molecular level to behavior is complex to say the least. Dias and Ressler were careful to describe the behavioral phenomenon in the offspring of the fear-conditioned mice as an increased sensitivity, not specifically a fear of the odor. At this point, they were not able to determine a molecular mechanism or specific cause of the behavioral change.



The paper appeared online December 1^st, almost three weeks after Dias’ SfN talk and the ensuing controversy and armchair critiquing. However, during most of that time the authors were essentially handcuffed by the journal’s press embargo policy until the paper was published online on December 1^st. Granted, it is rare that a presentation at a conference would generate this much excitement before the paper was published, but it seems that even with early online publication of articles, peer-reviewed journals have trouble keeping up with 21^st century, 140-character communication. The rapid, yet accurate dissemination of results will likely be an issue that journals continue to struggle with, while occasionally leaving authors in limbo.



In addition to the discussion surrounding publication of a controversial paper, the journal club also delved into some of the ethical issues that may arise from studies such as this one. For example, should the children of veterans who have suffered from PTSD be treated as an “at-risk” group, and what would that entail? Or, should members of the military be screened for a family history of trauma based on the idea that those individuals whose parents experienced traumatic events may be more vulnerable to adverse outcomes during or after their tour of duty? It seemed that there was agreement that when a plausible mechanism for how a fear memory – and particularly one associated with a certain smell – could impact the epigenetic marks in sperm cells in order to be passed on to subsequent generations, and then tested, the field would be better able to understand intervention opportunities. Trauma and stress are major public health issues just based on what we know about how they can shape an individual’s behavioral and physiological responses to later challenges in life^10,11. If in fact trauma and adversity can also shape our children’s sensory experience of the world through heritable, epigenetic changes, then it will be even more important to understand how the effects can be mitigated.



Additionally, accurate and clear communication of results to the public remains as important as ever. While the avenues for communication have changed drastically in recent years, and in many ways have made communicating easier, publishers and authors will likely continue to grapple with the new speed and power of social media. What role, if any, should these platforms play in the communication of science? If one of the goals is to engage the public’s interest then it seems that social media presents a great opportunity to do that but there are obvious concerns. While it may not be possible to fit detailed methods and results into 140 characters, new initiatives such as PubMed Commons may help reduce the formality and finality associated with published papers and increase discussion among scientists. Still, it will be interesting to see how social media is adopted by scientists and whether it helps at all in bridging our current communication gap with the public.





References



1. Jones, S. V., Choi, D. C., Davis, M. & Ressler, K. J. Learning-dependent structural plasticity in the adult olfactory pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 28, 13106-13111, doi:10.1523/JNEUROSCI.4465-08.2008 (2008).

2. Jirtle, R. L. & Skinner, M. K. Environmental epigenomics and disease susceptibility. Nature reviews. Genetics 8, 253-262, doi:10.1038/nrg2045 (2007).

3. Heard, E., Martienssen, R.A. Transgenerational Epigenetic Inheritance: Myths and Mechanisms. Cell 157, 95-109 (2014).

4. Ng, S. F. et al. Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467, 963-966, doi:10.1038/nature09491 (2010).

5. Wei, Y. et al. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proceedings of the National Academy of Sciences of the United States of America 111, 1873-1878, doi:10.1073/pnas.1321195111 (2014).

6. Greer, E. L. et al. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479, 365-371, doi:10.1038/nature10572 (2011).

7. Dietz, D. M. et al. Paternal transmission of stress-induced pathologies. Biological psychiatry 70, 408-414, doi:10.1016/j.biopsych.2011.05.005 (2011).

8. Jovanovic, T. et al. Physiological markers of anxiety are increased in children of abused mothers. Journal of child psychology and psychiatry, and allied disciplines 52, 844-852, doi:10.1111/j.1469-7610.2011.02410.x (2011).

9. Dias, B. G. & Ressler, K. J. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature neuroscience 17, 89-96, doi:10.1038/nn.3594 (2014).

10. Gluckman, P. D., Hanson, M. A., Cooper, C. & Thornburg, K. L. Effect of in utero and early-life conditions on adult health and disease. The New England journal of medicine 359, 61-73, doi:10.1056/NEJMra0708473 (2008).

11. Murgatroyd, C. et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature neuroscience 12, 1559-1566, doi:10.1038/nn.2436 (2009).





Want to cite this post?



Purcell, R. (2014). Lamarckian sh*t? Why epigenetics is not eugenics. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/03/lamarckian-sht-why-epigenetics-is-not.html

Neuroethics Journal Club: How early can signs of autism be detected in infants?

Autism Spectrum Disorder (ASD) is a complex disorder typically characterized by social impairment and communication deficits, and most recently the CDC has estimated that 1 in 88 American children are affected by a form of ASD.¹ A reliable diagnosis for autism can be offered at 24 months, but most children are diagnosed later after attending school. For the first Neuroethics journal club of the spring semester, ILA graduate student and Neuroethics Scholar Jennifer Sarrett led a discussion on a new technology that could offer preclinical risk assessment in children as young as 2 months.



Even though children and adults with autism exhibit a wide variety of individual and unique symptoms, a common attribute of those diagnosed with autism is a deficit in the ability to make eye contact. In a paper published in Nature late last year, researchers from the Marcus Autism Center and Emory University School of Medicine used special eye-tracking equipment to measure eye fixation in children only 2 months of age and were able to observe the earliest signs of developing autism ever recorded.² Infants that were enrolled in the study were measured at 10 different time points between the ages of 2 months and 24 months, and then an autism diagnosis was made at 36 months. Infants were classified as either high-risk for ASD if a full sibling had already been diagnosed with ASD or low-risk if no first, second, or third degree relatives were affected by the disorder. Eye-tracking was analyzed at each of the time points for 36 boy infants, 11 of which were later diagnosed with ASD (10 from the high-risk group and 1 from the low-risk group) and 25 of which were classified as typically developing. At each of these time intervals, infants watched videos of a caregiver behaving in a natural, standard manner, and the amount of time each infant fixated visually on the eyes, mouth, body, and objects in the room was measured. It was hypothesized that in the children later diagnosed with autism, a deficit in the attention given to the caretaker’s eyes would be observed beginning from the earliest time point measured.

In 2002, the first study of this kind to use eye-tracking equipment to research autism was conducted.³ Male adolescents with autism and males that had not been diagnosed with autism were recruited to watch 5 clips from the 1967 movie “Who’s Afraid of Virginia Woolf,” chosen due to the socially intense interaction of the four main characters.⁴ The movie includes many highly complex social situations that would warrant a viewer’s fixation on a character’s facial expression and bodily actions. While those in the study watched the clips, eye-tracking equipment was utilized to track visual fixation of the two groups. Individuals from the autism group were more fixated on the mouth region, the body region, and object region than their peers that had not been diagnosed with autism. The largest difference in visual fixation was that of the eyes though; those from the autism group fixated 2 times less on the eyes and this was the best predictor of which study group an individual was associated with.

Yellow = Control viewer, Orange = Viewer with autism³

Just like in the seminal 2002 experiment, when tracking the eye movement of infants watching a naturalistic caregiver, researchers observed a stark difference in the visual fixation patterns of the infants later diagnosed with autism and the typically developing control group.  In typically developing male infants, eye fixation was highest from 2 to 24 months compared to mouth, body, or object fixation. Mouth fixation increased from 2 to 12 months and was highest at approximately 18 months, while body and object fixation declined from the 2 to 24 month period. In the infants later diagnosed with ASD, eye fixation declined at the 2 month mark until the end of the testing period, eventually reaching a level that was half of the typically developing group. Similar to the control group, body fixation declined, but at half the rate of typically developing infants and at 24 months was 25% higher. Object fixation also declined initially from 2 to 18 months, but then increased and at 24 months was twice as high as the control group. Similarly to the typically developing male infants, infants later diagnosed with autism also showed a mouth fixation increase from 2 to 18 months. Although researchers observed a different pattern for visual fixation in each of the four regions, especially fixation to the caregiver’s eyes, over the 2 year period when comparing the control group and those later diagnosed with autism, notably at the 2-month mark, infants with autism show visual fixation to eyes in the normative range. All infants regardless of which group they belonged to in the study began with a visual fixation time to the eyes between approximately 40 and 50%, but only those with autism showed a sharp decline after 2 months. This finding disproves a long held hypothesis by those well familiar with autism – that this particular symptom of autism begins immediately following birth. This study instead suggests that there is a small window, from birth to 2 months, where visual fixation to the eyes in not impaired, and could be very exciting in terms of treatment for autism since as the authors of the paper state “predispositions that are initially intact suggest a neural foundation that may be built upon, offering far more positive possibilities than if that foundation were absent from the outset.”²



A new technology that has the potential to be used as a screening tool for autism would be incredibly helpful for the field, since it has been shown that early diagnosis and early therapies can improve a child’s delayed development.⁵ However, therapies for autism including speech and language therapy, usually occur between 12 and 18 months, at the earliest. If risk assessment is made between the ages of 2 and 6 months and the only obvious symptom is declining eye contact that has been made with specialized, sophisticated technology that currently is not even used in a clinician’s office, what therapies would be utilized and what development skills would therapy target? The earlier autism is detected, the better for the child, but is it also possible that there would be an age where the diagnosis would be unnecessary, or even detrimental? As this new technology is more widely used and if the results are confirmed in a larger population, researchers are more likely to develop intensive therapies for infants in an effort to rehabilitate children who show signs of autism at a very young age.



ASD can be expressed in children and adults in a variety of forms with varying levels of severity. While parents of a severely autistic child who is unable to communicate would most likely appreciate intensive therapies given at a young age in an effort to lessen the effects of autism, many advocates of neurodiversity would rather find ways to accommodate and help those afflicted with autism and not find new methods for extreme rehabilitation. Proponents of neurodiversity often believe that many neurological disorders, such as ASD, are a natural result of the genome and neurodiversity is crucial to society.^6,7 Attempts to eliminate all autistic expression from children using early-intervention autism assessment or therapy would go against the tenets of neurodiversity and be seen as completely unnecessary.



The idea of neurodiversity and how neurodiversity applies to autism is a complex idea, in part because autism is such a diverse disorder. No two children with autism behave the same or are affected at the exact same level of severity. As researchers and clinicians move forward with very early therapeutic interventions and even earlier risk assessments, children will have to be considered individually. Screening for autism at an infant age may be useful or even necessary for children with a high-risk for autism, and based on the results, it may not be advisable to wait until a child reaches 12 to 18 months to start therapy. While researchers observed that a steeper decline in visual eye fixation was related to a more severe social disability, results also suggest that initial visual fixation to the eyes following birth into the first couple of months of life is not reliant on whether or not a child has autism. This offers the hope that there are more therapies for autism to be explored – those that build on a neural foundation and normative social behavior observed in infancy, and not necessarily a remedial program that works to adjust social behavior and visual fixation deficits.





References:



1) Autism Spectrum Disorders (ASDs). Centers for Disease Control and Prevention ASD homepage. Retrieved on January 28, 2014, from http://www.cdc.gov/ncbddd/autism/facts.html



2) Jones, W., Klin, A. (2013). Attention to eyes is present but in decline in 2-6-month-old infants later diagnosed with autism. Nature 504, 427.



3) Falck-Ytter, T., Bölte, S., Gredebäck, G. (2013). Eye tracking in early research. J Neurodev Disord 5, 28.



4) Klin, A., Jones, W., Schultz, R., Volkmar, F., Cohen, D. (2002). Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism. Arch Gen Psychiatry 59, 809.



5) What is Autism? Autism Speaks. Retrieved on January 28, 2014, from http://www.autismspeaks.org/what-autism



6) Sarrett, J. (2013). Why is Neurodiversity Useful? The Neuroethics Blog. Retrieved on January 28, 2014, from http://www.theneuroethicsblog.com/2013/12/why-is-neurodiversity-useful.html



7) My Life With Asperger's. Psychology Today. Retrieved on January 28, 2014 from http://www.psychologytoday.com/blog/my-life-aspergers/201310/what-is-neurodiversity.







Want to Cite This Post?



Strong, K. (2014). Neuroethics Journal Club: How early can signs of autism be detected in infants? The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2014/02/neuroethics-journal-club-how-early-can.html

Neuroethics Journal Club Report: "Creating a false memory in the hippocampus" Ramirez et al. Science 2013

Our memory can be unreliable, that comes as no surprise. But beyond forgetting where the car is parked or misremembering a date, a perhaps more interesting phenomenon is that of false memories of events that have never happened, or at least not to us directly. In most cases, the fallibility of memory is benign or occasionally embarrassing, but in the courtroom it can have serious consequences. In the final Neuroethics Journal Club of the semester, Emory University graduate student and AJOB Neuroscience editorial intern, Katie Strong, led a thought-provoking discussion of Ramirez’s 2013 Science paper¹ entitled “Creating a false memory in the hippocampus” with a focus on the potential neuroethical implications of this research on the justice system.

The discussion paper comes from 1987 Nobel laureate Susumu Tonegawa’s lab and is in some ways a sequel to their 2012 paper published in Nature². In both studies this group utilized an elegantly-designed mouse model with the aim of targeting the cells in the hippocampus constituting the memory engram. The search for the engram, or memory trace in the brain, is not a recent pursuit. Karl Lashley’s seminal mid-20^th century work suggested that memories are dispersed throughout the cortex. Lashley’s lesion studies surprisingly indicated that the amount of cortex damaged mattered far more than the location of the lesions³.



More recently the search has moved toward molecular changes in individual cells and at particular synapses⁴.  It is now thought that Lashley’s findings may have been the result of the complexity of the tasks that his animals performed, which involved multiple brain regions, since emerging evidence suggests that in some circumstances the same particular cells are activated during recall of certain memories⁵. Conversely, fear conditioning is a relatively simple paradigm that has been widely used because animals rapidly learn to pair an innocuous cue such as a light, tone, or an environment with an aversive stimulus such as a foot shock. Moreover, the neural circuitry controlling these behaviors has been extensively studied⁶.



In this paper, Ramirez and colleagues used a very similar approach to that in their 2012 paper in which they employed optogenetics (a technique to genetically target a group of cells that can later be activated by pulses to light) to label and reactivate hippocampal engram neurons². Mice were unilaterally injected into the dentate gyrus of the hippocampus with a virus to drive the expression of a fluorescently-tagged, light-activated protein (channelrhodopsin-2) under the control of a drug-responsive promoter. These mice had been genetically engineered to activate this expression system when the immediate early gene c-fos, a marker of neuronal activity, is induced. The result was that expression of the light-activated channelrhodopsin-2 only occurs when (1) the animals are taken off of the expression-suppressing drug doxycycline and, (2) when neurons are sufficiently activated to induce expression of c-fos. This allowed the experimenters to essentially label the memory engram of a neutral context (context A) by removing doxycycline from the animals’ diet. Then, when doxycycline was replaced and neuronal labeling was halted, they were able to selectively re-activate the neutral context engram-bearing cells with rapid pulses of light.



In order to induce a false memory, the animals were removed from context A and placed in context B where the engram cells that encoded for context A were selectively stimulated with light while a foot shock was delivered. Later, when the animals were placed back in context A they demonstrated a typical fear response for rodents - freezing, even though they had actually experienced the foot shock in context B. The experimental group of mice exhibited a higher level of freezing than those animals that lacked the engram-labeling genetic engineering and were thus nonresponsive to the subsequent artificial light stimulation. As others⁷ have pointed out, this is not the first time that fear conditioning has been achieved with artificial stimulation in place of the conditioned stimulus, but it is the first time that this is been done by directly activating individual neurons in the brain.



These experiments may seem to be far-removed from typical human experience, but they may provide the basis to understand how false memories can be formed. As the authors point out, recall is known to make memories more labile and external information can occasionally be incorporated into existing memories over time. Moreover, they argue that these results may in fact be relevant to humans. In their words,

“we speculate that the formation of at least some false memories in humans may occur in natural settings through the internally driven retrieval of a previously formed memory and its association with concurrent external stimuli of high valence.”

For example, experimental psychologists have often been able to induce false memories in study participants through the use of leading questions and suggestion at a success rate of nearly 1 in 3⁸. Often these paradigms use realistic and traumatic circumstances such as being lost as a small child in a mall. Perhaps the simultaneous recollection of a fear of being lost as a small child and memories of going to the mall at that age is enough to implant a false memory in some individuals.



Beyond the laboratory, false identification is an obvious and persistent problem for the justice system. The Journal Club discussion centered on a recent New Jersey case, State v. Henderson, which led to major reforms being enacted to change how eyewitness testimony is evaluated based on social science and psychology research⁹. This particular case involved the reliability of an eyewitness who encountered the suspect at gunpoint in a dark hallway when he had been drinking alcohol and smoking crack cocaine, and who continued to use crack daily until the police first contacted him more than a week later. Moreover, the witness reportedly struggled with a photo identification procedure and was pressured by the police to make a decision.



This case provides a hopeful example for how scientific research can spur progress improving accuracy and judicial outcomes, but what relevance does the Ramirez article really hold for understanding false memory? In these studies, the experimental group of animals – that which later displayed a false memory – had the memory of a neutral context linked to a foot shock by reactivating specific neurons using artificial means (optogenetics). This ability to activate a memory only by stimulating those (relatively few) neurons that were active during its encoding is strong, direct evidence for the existence and identification of the engram that can then be linked to a situation of high valence, such as a foot shock, to create a false fear memory. In reality, however, this is not how false memories are encoded in humans. It is an important step forward that elegantly demonstrates that the neurons involved in encoding a contextual fear memory are also sufficient for recall, but this technology is certainly not close to being used in humans. However, researchers have already found other ways to experimentally manipulate false memories in humans.

Transcranial magnetic stimulation (Source: TIME Magazine)

No one will be having viral injections and fiber optic cables implanted into their hippocampi anytime soon, but transcranial magnetic stimulation (TMS) is a safe, non-invasive technology that has already been used to affect false memory acquisition in humans¹⁰. Gallete and colleagues reasoned that since patients with left anterior temporal lobe (LATL) dementia often become very literal and less vulnerable to false memories, perhaps temporary inactivation of this brain area with TMS would reduce the rate of false memory acquisition and indeed it did. These results suggest that localized TMS to the LATL during learning could aid in factual recall so should it be more widely available to students?



Understanding how memories are encoded, consolidated, retrieved – and how this process can go awry – has long been a fundamental aim of neuroscience. New technologies such as optogenetics and TMS are allowing investigators to ask questions that were never possible until now. However, there is still much to learn in terms of how false memories are formed and how they can be minimized. While this aim will require continued work from social scientists, psychologists, and neuroscientists, neuroethical discussions will also be important in framing how false memories are understood and addressed from the laboratory to the courtroom.





References



1. Ramirez, S. et al. Science 2013.

2. Liu, X. and Ramirez, S. et al. Nature 2012.

3. Lashley, K.S. Physiological mechanisms in animal behavior 1950.

4. Govindarajan, A. et al. Nature Reviews Neuroscience 2006.

5. Josselyn, S.A. Journal of Psychiatry & Neuroscience 2010.

6. Kim, J.J. and Jung, S.W. Neuroscience and Biobehavioral Reviews 2006.

7. Saksida, L.M. Trends in Cognitive Science 2013.

8. Loftus, E.F. American Psychologist 2003.

9. Harvard Law Review 125:1514, 2012.

10. Gallate, J. et al. Neuroscience Letters 2009.





Want to cite this post?



Purcell, R. (2014). Neuroethics Journal Club Report: "Creating a false memory in the hippocampus" Ramirez et al. Science 2013. The Neuroethics Blog. Retrieved on

, from http://www.theneuroethicsblog.com/2014/01/neuroethics-journal-club-report.html

Neuroethics Journal Club: Neural Correlates of Negative Stereotype

Our everyday perceptions of others
can potentially be biased by cultural stereotypes. However, research has
suggested that an initial, and often negative, stereotype can be downregulated
via a highly connected neural network. While this regulatory process has been studied
under neutral conditions, for the third journal club of the semester
Neuroscience graduate student Kim Lang led a discussion about regulation of
this neural network when White individuals are not under neutral conditions,
but actually primed for negative African American stereotyping.




A recent paper published by Forbes et al. used functional magnetic
resonance imaging (fMRI) to study the amygdala, the prefrontal cortex (PFC),
and the orbitofrontal cortex (OFC), three highly interconnected brain regions
important for stereotyping and bias. Studies have shown that the amygdala,
involved in arousal, is activated immediately when encountering a so-called
out-group member. This first response can be downregulated though if an
individual is given time for non-biased deliberation, and this is reflected by
activation in the PFC. The OFC is the regulator of these two neural regions,
especially if initial negative stereotyping is in conflict with an egalitarian
view. Prior research has shown this amygdala inhibition by the lateral PFC
region with an experiment where White participants were shown Black faces in
either rapid succession (30 ms) or at a slower rate (525 ms). When participants
did not have time to reflect on the faces during the fast exposure speeds,
enhanced amygdala activation was observed reflecting the early arousing
response. During the slow exposure time condition though, amygdala activity was
not enhanced.  Instead, increased activity
was observed in the dorsolateral prefrontal cortex (DLPFC), which correlates
with decreased amygdala activation (Cunningham et al.). This study suggests that if given enough time, a biased
view reflected in the activation of the amygdala, can be reconsidered.

Adapted from The Jury Expert

The authors of the paper for
journal club discussion (Forbes et al.)
took this previous experiment further and studied the activation of the
amygdala when White participants were exposed to Black faces at either 30 ms or
525 ms in the presence of violent and misogynistic rap (VMR) to create a
situation that is primed for negative African American stereotyping. While
evidence shows that individuals are able to downregulate the initial arousal
and response to stereotypes, researchers hypothesized that if stereotypical or
suggestive music were playing, then individuals would be less likely to downregulate
the response even if given ample time to consider the situation. In other words,
during the slow showing of Black faces in the presence of VMR, White
participants would show a prolonged amygdala response instead of a downregulation.  “Straight Outta Compton”
by NWA was rated high by participants and chosen as the song to represent Black
American stereotyping in the study. To prime for negative stereotyping, but not
African American stereotyping, participants were also asked to rate a death
metal (DM) song, since this genre of music is typically associated with White
American culture. “Only
One” by Slipknot was chosen based on a similarity in tempo and violent
references to “Straight Outta Compton.” Participants were then shown
expressionless Black and White male faces at either the fast (30 ms) or the
slow (525 ms) rate while listening to VMR, DM, or no music (NM) while the fMRI
scans were completed. After the scanning, participants were asked general
questions regarding their feelings toward the song, whether they owned any of
the songs (no participants did), and how they rated themselves on the Modern
Racism Scale³ and the Motivation to Respond Without Prejudice
Scale⁴.




Based on the responses to the two
rating systems, participants reported being non-prejudiced and motivated to
regulate their biases, and the fMRI scans of the amygdala during the slow scan
with NM reflected this. Consistent with previous work (Cunningham et al.), when participants were exposed
to the faces at the fast rate, amygdala activation was observed and during the
slow speed, OFC and DLPFC activation was recorded. When participants were
exposed to Black and White faces at the fast speed in the presence of DM, no
activation at the amygdala, OFC, or the DLPFC was observed. Similar to NM, at
the slow speed during DM, activation of the OFC and DLPFC regions was still
greater when seeing the Black faces compared to White faces, suggesting that
participants were still engaging in a deeper processing of the Black faces. The
focus of the hypothesis was the activation of brain regions in participants
when VMR was playing. As predicted, when Black faces were displayed during the
fast exposure, greater amygdala activation was observed compared to White faces.
During the slow speed, participants still showed higher amygdala activity when
seeing Black faces compared to White faces, but also increased OFC and DLPFC
activation.




When comparing results across the
two types of music and the context with no music, greater amygdala activation
was seen during the fast and slow exposures for VMR than for NM and DM. As
expected, greater DLPFC activity was seen for the fast and slow exposures for
NM and DM compared to VMR. Interestingly, when exposed to the fast speed,
greater OFC activation was seen for VMR compared to NM and DM. However, during
the slow speed exposure, the opposite was observed, and greater OFC activity
was seen for NM and DM compared to VMR. These findings suggest that not only is
there a continuum of neural processing during slow and fast social cognitive
assessments, but the lack of downregulation in the amygdala during the fast and
slow speed exposure for VMR is evidence that although White individuals can control
an initial, arousing reaction to a Black individual in a neutral context, this
is more difficult when the situation lends itself to negative stereotyping. The
authors offer two possible interpretations for this lack of downregulation in
the VMR scenario. Either exposure to the VMR causes a prolonged amygdala
response that is cognitively taxing on other neural regions, making it
difficult to control a response or the VMR justifies the initial response and
reinforces that stereotype.

From Forbes et al.

Whether a situation that is primed
for negative stereotyping makes deliberation more cognitively taxing or
justifies an initial stereotype, brain activation isn’t predictive for
behavioral responses since similar activation patterns in individuals do not
always give rise to similar behaviors. Although this study was more
representative of everyday circumstances than the previous study with neutral
conditions, it would be interesting to measure the neural activity of
individuals when encountering situations that prime for negative
stereotypes.  Even if there is typically
a lack of amygdala downregulation, does this mean that individuals still
behaviorally restrain themselves?




A second experiment that was
discussed during journal club as a potential follow-up to this paper would be
to repeat the fast and slow exposures of Black faces during the three different
musical contexts, but with Black participants instead of White participants.
“Straight Outta Compton” is not subtle, but instead overtly violent and
misogynistic, and it could be that people
of all races would have an arousing response in the amygdala that would be
difficult to regulate strictly due to the nature of the lyrics – not because
the song stereotypes African American culture. Of course it is a matter of
opinion whether “Only One” really mimics “Straight Outta Compton,” or whether
“Straight Outta Compton” is truly violent and misogynistic, so the experiments
could be repeated with more and different songs to help confirm the hypothesis
that “when something as subtle as a rap song is played in the background,”
White individuals negatively stereotype Black Americans (Forbes et al.).




More research will most likely be
done in the future, but these results do have larger implications to consider for
society today. Knowing that even in tolerant individuals with an egalitarian
viewpoint the amygdala is activated and can be difficult to downregulate, does
this mean that neural activation would justify racial violence, especially in a
court case? Should defense attorneys ever be able to claim that this activity
in a context that primes for negative stereotyping is a valid defense for a
violent or egregious crime against an out-group member? As neuroscience
research becomes more sophisticated, more debates will follow about where we
draw the line for allowing scientific research as evidence in the courtroom and
when we must hold the individual solely responsible. In the meantime, hopefully
when encountering an out-group member, we will consider that negative
stereotypical contexts may prime us for negative stereotyping due to a complex
neural interaction that is somewhat out of our control. If we are conscious
that we have difficulties mediating initial responses, perhaps more conscious tolerance
and reflection could follow a circumstance where an initial judgment seems
justified based on contextual cues.






References

1. 
   Forbes, C.E., Cox, C.L., Schmader, T., Ryan, L.
   (2011). Negative stereotype activation alters interaction between neural
   correlates of arousal, inhibition and cognitive control. Social Cognitive and Affective Neuroscience, 7, 771.
   




2. 
   Cunningham,
   W.A., Johnson, M.K., Raye, C.L., Gatenby, J.C., Gore, J.C., Banaji, M.R.
   (2004). Separable neural components in the processing of Black and White faces. Psychological Science, 15, 806–13.
   




3. 
   McConahay,
   J.B. (1986). Modern racism, ambivalence, and the modern racism scale. In:
   Dovidio, J.F., Gaertner, S.L., editors. Prejudice, Discrimination, and Racism (pp. 91–125). Orlando,
   FL: Academic Press.
   




4. 
   Plant,
   E.A., Devine, P.G. (1998). Internal and external motivation to respond without
   prejudice. Journal of Personality and Social Psychology, 75, 811–32. 

Want to cite this post?



Strong, K. (2013). Neuroethics Journal Club: Neural Correlates of Negative Stereotype. The Neuroethics Blog. Retrieved on
, from http://www.theneuroethicsblog.com/2013/12/neuroethics-journal-club-neural.html