(Image caption: Brain image showing activity in the amygdala, the area of the brain involved with emotion. The amydgala was more active during the graphic scenarios only when the harm being described was intentional. Credit: Marois Lab / Vanderbilt)

Fault trumps gruesome evidence when it comes to meting out punishment

Issues of crime and punishment, vengeance and justice date back to the dawn of human history, but it is only in the last few years that scientists have begun exploring the basic nature of the complex neural processes in the brain that underlie these fundamental behaviors.

Now a new brain imaging study – published online Aug. 3 by the journal Nature Neuroscience – has identified the brain mechanisms that underlie our judgment of how severely a person who has harmed another should be punished. Specifically, the study determined how the area of the brain that determines whether such an act was intentional or unintentional trumps the emotional urge to punish the person, however gruesome the harm may be.

“A fundamental aspect of the human experience is the desire to punish harmful acts, even when the victim is a perfect stranger. Equally important, however, is our ability to put the brakes on this impulse when we realize the harm was done unintentionally,” said Rene Marois, the Vanderbilt University professor of psychology who headed the research team. “This study helps us begin to elucidate the neural circuitry that permits this type of regulation.”

The study

In the experiment, the brains of 30 volunteers (20 male, 10 female, average age 23 years) were imaged using functional MRI (fMRI) while they read a series of brief scenarios that described how the actions of a protagonist named John brought harm to either Steve or Mary. The scenarios depicted four different levels of harm: death, maiming, physical assault and property damage. In half of them, the harm was clearly identified as intentional and in half it was clearly identified as unintentional.

Two versions of each scenario were created: one with a factual description of the harm and the other with a graphic description. For example, in a mountain climbing scenario where John cuts Steve’s rope, the factual version states, “Steve falls 100 feet to the ground below. Steve experiences significant bodily harm from the fall and he dies from his injuries shortly after impact.” And the graphic version reads, “Steve plummets to the rocks below. Nearly every bone in his body is broken upon impact. Steve’s screams are muffled by thick, foamy blood flowing from his mouth as he bleeds to death.”

After reading each scenario the participants were asked to list how much punishment John deserved on a scale from zero (no punishment) to nine (most severe punishment the subject endorsed).

Analysis of the responses

When the responses were analyzed, the researchers found that the manner in which the harmful consequences of an action are described significantly influences the level of punishment that people consider appropriate: When the harm was described in a graphic or lurid fashion then people set the punishment level higher than when it was described matter-of-factly. However, this higher punishment level only applied when the participants considered the resulting harm to be intentional. When they considered it to be unintentional, the way it was described didn’t have any effect.

“What we’ve shown is that manipulations of gruesome language leads to harsher punishment, but only in cases where the harm was intentional. Language had no effect when the harm was caused unintentionally,” summarized Michael Treadway, a post-doctoral fellow at Harvard Medical School and lead author of the study.

According to the researchers, the fact that the mere presence of graphic language could cause participants to ratchet up the severity of the punishments suggests that photographs, video and other graphic materials sampled from a crime scene is likely to have an even stronger impact on an individual’s desire to punish.

“Although the underlying scientific basis of this effect wasn’t known until now, the legal system recognized it a long time ago and made provisions to counteract it,” said Treadway. “Judges are permitted to exclude relevant evidence from a trial if they decide that its probative value is substantially outweighed by its prejudicial nature.”

Underlying neuroanatomy

The fMRI scans revealed the areas of the brain that are involved in this complex process. They found that the amygdala, an almond-shaped set of neurons that plays a key role in processing emotions, responded most strongly to the graphic language condition. Like the punishment ratings themselves, however, this effect in the amygdala was only present when harm was done intentionally. Moreover, in this situation the researchers found that the amygdala showed stronger communication with the dorsolateral prefrontal cortex (dlPFC), an area that is critical for punishment decision-making. When the harm was done unintentionally, however, a different regulatory network – one involved in decoding the mental states of other people – became more active and appeared to suppress amygdala responses to the graphic language, thereby preventing the amygdala from affecting decision-making areas in dlPFC.

“This is basically a reassuring finding,” said Marois. “It indicates that, when the harm is not intended, we don’t simply shunt aside the emotional impulse to punish. Instead, it appears that the brain down-regulates the impulse so we don’t feel it as strongly. That is preferable because the urge to punish is less likely to resurface at a future date.”

Do we really only use 10% of our brain?

As the new film Lucy, starring Scarlett Johansson and Morgan Freeman is set to be released in the cinemas this week, I feel I should attempt to dispel the unfounded premise of the film – that we only use 10% of our brains. Let me state that there is no scientific evidence that supports this statement, it is simply a myth.

The concept behind the film is that through the administration of a new cognitive enhancing drug, our female lead character, Lucy, becomes able to harness powerful mental capabilities and enhanced physical abilities. These include telekinesis, mental time travel and being able to absorb information instantaneously. Viewed as such, the human brain should be essentially capable of these feats, we just fail to push our capacity. So if we can unlock the “unused” 90% of the brain we too could be geniuses with super powers?

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Not too early for maths

Bad maths grades, poor participation in class, no interest in arithmetic. Preterm children often suffer from dyscalculia – at least according to some scientific studies. A misunderstanding, claims developmental psychologist Dr Julia Jäkel, who has been studying the performance of preterm children.

Thanks to modern medicine, the percentage of preterm survivors is constantly increasing. On the cognitive level, these children frequently have long-term problems such as poor arithmetic skills and difficulty concentrating. For a long time, research focused on high-risk children, born before 32 weeks gestational age or with less than 1,500 gram. Current studies from the most recent years, however, show that this approach is too short-sighted.

Dr Julia Jäkel from the Department of Developmental Psychology has analysed cognitive abilities of children born between 23 and 41 weeks gestation. In doing so, she covered the entire spectrum, ranging from extremely preterm to healthy term born infants. For this purpose, she used data of the Bavarian Longitudinal Study, which has been following a birth cohort from the late 80s until today. “Having access to such a comprehensive long-term study is a dream come true for every developmental psychologist,” says the Bochum researcher. Over the course of the study, all children underwent a whole battery of tests that assessed their cognitive and educational abilities, and their parents were interviewed in depth.

The RUB researcher has so far mainly focused on data collected at preschool and early school age. For different test tasks, she assessed their cognitive workload, a criterion for the complexity of a given task. The data showed that preterm children had greater difficulties with tasks that demanded higher working memory resources. Moreover, results revealed that not only high-risk children had significant difficulties. On average, the more preterm a child had been born, the poorer were his or her abilities to solve complex tasks.

But what exactly is the nature of these difficulties? It has been frequently suggested that preterm children suffer from dyscalculia. A phenomenon that Julia Jäkel examined more closely. “Mathematical deficiencies, maths learning disorder, dyscalculia, innumeracy – these terms’ definitions vary slightly,” she explains, but there are no standardised, internationally consistent diagnostic criteria. In order to assess specific maths deficiencies, children in Germany are assessed with a number of tests. If their results fall below a certain cut off value in maths while their cognitive skills (IQ) are in the normal range, they are diagnosed with “maths learning disorder” or “dyscalculia”.

“The problem with preterm children, however, is that they often have general cognitive deficits,” Julia Jäkel points out. “According to current criteria, these children can’t be diagnosed.” Together with Dieter Wolke from the University of Warwick, UK, she compared different diagnostic criteria for dyscalculia in her analysis. The aim of the study was to identify specific maths deficiencies in preterm children that were independent of general cognitive impairments. With surprising results: “There is no specific maths deficit in preterm children if their general IQ is factored in,” says the researcher.

This means that preterm children do not suffer from dyscalculia more often than term children. However, they often have maths difficulties and these may not be recognized. This is because the current criteria make it impossible to diagnose dyscalculia if a child also has general cognitive deficits. Thus, these children do not receive specific help in maths although they may be in urgent need. “We need reliable and consistent diagnostic criteria,” demands Julia Jäkel. “And we’ve got to find ways to actually deliver support in schools.”

Together with her British team, the psychologist compared the results of the Bavarian Longitudinal Study with “EPICure” data, a similar study that commenced in the UK in the 1990s, following a cohort of extremely preterm children. The researchers focus on mathematical and educational performance. British preterm children had similar cognitive and basic numerical skills as German preterm children. In terms of maths achievement, however, they showed significantly better results. “We explain this with the fact that, unlike in Germany, in the UK it has not been possible for children to delay school entry,” explains Julia Jäkel. “In addition, special schools are attended by only a small percentage of extremely disabled children. All other children are integrated into normal classes in regular schools and receive targeted support there.”

The developmental psychologist has already demonstrated that assistance at primary-school age can really make a difference. Parents who support their preterm children with sensitive scaffolding can compensate the negative cognitive effects of preterm birth. It is helpful, for example, if parents give their children appropriate feedback to homework tasks and suggest potential solutions, rather than solving the tasks for the child. However, Julia Jäkel believes that a lot of research is yet to be done as far as intervention is concerned: “A large percentage of parents is very dedicated and has resources to help their children,” she says. “But research has not yet produced anything that would ensure successful results in the long-term.” Together with colleagues from the university hospital in Essen, the RUB researcher plans to investigate the benefits of computer-aided working memory training for preterm children’s school success, which has already been successfully applied on an international level.

It would also be helpful if findings from related disciplines, such as developmental psychology, educational research, and neonatal medicine were better integrated. This is, for example, because neonatal medical treatment can significantly affect later cognitive performance. Together with her interdisciplinary team, Julia Jäkel used a comprehensive model to analyse to what extent different neonatal medical indicators affect cognitive development at age 20 months, attention abilities at age six, and maths abilities at age eight years. In her analyses, she factored in child sex and socio-economic status.

Results showed that neonatal medical variables, e.g., the duration of mechanical ventilation, predicted cognitive abilities at age 20 months. Both factors together predicted attention regulation at age six years. And all those precursors, in turn, affected long-term general maths abilities.

Subsequently, Julia Jäkel analysed the data once again from a different perspective, in order to predict specific maths skills that were independent of the child’s IQ. In that model, only two variables had direct impact: the duration of mechanical ventilation and hospitalisation after birth. In the 1980s, when children participating in the Bavarian Longitudinal Study were born, German doctors often used invasive ventilation methods. Today, less invasive methods are available, but to what extent they may affect long-term cognitive performance has not yet been investigated.

“Both too high and too low oxygen concentrations are harmful to brain development,” explains Julia Jäkel. “The neonatologist in charge is faced with the great challenge of determining the right dose for each infant, depending on individually changing situations.” This is why it is so important to integrate psychological models with neonatal intensive care research. The joint objective is to offer preterm children the chance of a successful school career, high quality of life and social participation.

(Figure 1: Axons grow and turn in response to guidance cues (arrows), which regulate endocytosis and exocytosis at the tips of growing axons. Credit: © 2014 T. Tojima et al.)

Steering the filaments of the developing brain

During brain development, nerve fibers grow and extend to form brain circuits. This growth is guided by molecular cues (Fig. 1), but exactly how these cues guide axon extension has been unclear. Takuro Tojima and colleagues from the RIKEN Brain Science Institute have now uncovered the signaling pathways responsible for turning growing nerve fibers, or axons, toward or away from guidance cues.

The researchers previously showed that axon-repelling cues act by inducing the removal of cell membrane—a process called endocytosis—from the side of the axon closest to the repulsive cue. The enzyme PIPKIγ90 is known to be involved in endocytosis in axons during certain types of synaptic activity, so the researchers investigated whether PIPKIγ90 also played a role in endocytosis during axon turning. By examining the developing brains of chicken embryos expressing an inactive form of PIPKIγ90, the researchers found that cues normally inducing endocytosis were no longer effective in repelling axon growth.

Cues that normally attract axons do so by driving membrane addition—exocytosis—on the side of the axon closest to the cue and also by suppressing endocytosis. Tojima’s team found that axons continued to be attracted to such cues even in the absence of PIPKIγ90, suggesting that PIPKIγ90 signaling is not involved in axon attraction.

The activity of PIPKIγ90 is known to be regulated by an enzyme called CDK5, a subunit of which binds to the protein kinase CaMKII. The researchers found that by inhibiting CDK5 or CaMKII, and thereby blocking the regulation of PIPKIγ90 that is needed to suppress endocytosis, endocytosis could occur in response to attractive cues.

They also found, however, that blocking CDK5 or CaMKII did not have any effect on endocytosis if the neurons expressed a mutant version of PIPKIγ90 that was unaffected by CDK5 and CaMKII signaling. As inhibitors of CDK5 or CaMKII did not alter endocytosis in response to repulsive cues, the team’s findings indicate that different signaling pathways are responsible for turning axons toward or away from guidance cues.

Additionally, Tojima and his colleagues showed that they could induce the attraction of axons toward drugs that inhibit endocytosis, suggesting that being able to control the direction of axon growth has potential therapeutic applications. “We hope our findings will aid in the development of future therapeutic strategies for rewiring neuronal networks after spinal cord injury and neurodegenerative diseases,” explains Tojima.

(Image caption: Positron-Emission-Tomography (PET) of a depressive patient without medication (left) with elevated monoamine-oxidase-A-levels (green, yellow, red) and after a six-week-treatment with the monoamine-oxidase-A-inhibitor moclobemid (right). Credit: © Sacher et al., 2011, J Psy Neurosci.)

Monoamine oxidase A: biomarker for postpartum depression

Many women suffer from baby blues after giving birth. Some even develop full-blown postpartum depression in the weeks that follow. Monoamine oxidase A, an enzyme responsible for the breakdown of neurotransmitters like dopamine and serotonin, plays an important role in this condition. In comparison to healthy women, women who experience postpartum depression present strongly elevated levels of the enzyme in their brains. This was discovered by a Canadian-German research team including Julia Sacher from the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig. Their findings could help in the prevention of postpartum depression and in the development of new drugs for its treatment.

For most women, the birth of their baby is one of the most strenuous but also happiest days in their lives. However, joy and happiness are often followed by fatigue and exhaustion. The vast majority of women experience a temporary drop in mood for a few days after birth. These symptoms of “baby blues” are not an illness; however, in some cases they can represent early signs of an imminent episode of depression: in 13 percent of mothers, the emotional turmoil experienced after childbirth leads to the development of a full-blown postpartum depression. Postpartum depression is harmful not only to the mother, but also to the baby. It is difficult to treat this condition effectively, as its precise neurobiological causes have remained unidentified to date.

The new study shows that postpartum depression is accompanied by strongly elevated monoamine oxidase A in the brain, particularly in the prefrontal cortex and in the anterior cingulate cortex. In women with postpartum depression, the values recorded were 21 percent higher than those of women who were not plagued by negative feelings after giving birth. Women who did not develop full-blown depression but found themselves crying more often than usual due to depressed mood also presented moderately elevated values.

“Therefore, we should promote strategies that help to reduce monoamine oxidase A levels in the brain, and avoid everything that makes these values rise,” explains Sacher. Such factors include heavy smoking, alcohol consumption and chronic stress, for example when the mother feels neglected and abandoned by her partner and family. “My ultimate goal is to provide women and their families with very concrete lifestyle recommendations that will enable them to prevent postpartum depression,” explains the psychiatrist.

A new generation of long-established drugs could also play an important role in the treatment of postpartum depression in future. Up to now, depressed mothers are mainly given drugs that increase the concentration of serotonin in the brain. However, because monoamine oxidase A breaks down not only serotonin but also other monoamines like dopamine and noradrenaline, a treatment that directly targets monoamine oxidase A could have a higher success rate, particularly in very serious cases: this alternative is provided by selective and reversible monoamine-oxidase- A inhibitors. “The first monoamine oxidase inhibitors often had severe side effects, for example hypertensive crises, which necessitated adherence to a strict diet,” explains Sacher. “However, the new selective and reversible drugs are better tolerated,” she adds. In the next stage of this research involving clinical trials, the scientists intend to test the effectiveness of these reversible monoamine oxidase A inhibitors in the treatment of postpartum depression.

Because the measurement of this enzyme in the brain requires complex technology, it is not suitable for routine testing. Thus, the researchers are also looking for a peripheral marker of this enzyme that can be detected in saliva or blood.

Four years ago, Julia Sacher and her colleagues at the Centre for Addiction and Mental Health CAMH in Toronto already succeeded in showing that, in the first week postpartum, the concentration of the enzyme monoamine oxidase A in the brain is on average 40 percent higher than in women who had not recently given birth. “The monoamine oxidase A values behave in the opposite way to oestrogen levels. When oestrogen levels drop acutely after childbirth, the concentration of monoamine oxidase A rises. This drastic change also influences serotonin levels, known as the happiness hormone,” explains Dr. Sacher. In most women, the values quickly return to normal. In others, they remain raised – and thereby promote the development of depression.

(Image credit: The insular cortex of an autism mouse model is already so strongly activated by a single sensory modality (here a sound), that it is unable to perform its role in integrating information from multiple sources. Credit: © MPI of Neurobiology / Gogolla)

Insular cortex alterations in mouse models of autism

The insular cortex is an integral “hub”, combining sensory, emotional and cognitive content. Not surprisingly, alterations in insular structure and function have been reported in many psychiatric disorders, such as anxiety disorders, depression, addiction and autism spectrum disorders (ASD). Scientists from Harvard University and the Max-Planck Institute of Neurobiology in Martinsried now describe consistent alterations in integrative processing of the insular cortex across autism mouse models of diverse etiologies. In particular, the delicate balance between excitation and inhibition in the autistic brains was disturbed, but could be pharmacologically re-adjusted. The results could help the development of novel diagnostic and therapeutic strategies.

Autism is a neurodevelopmental disorder characterized by impaired social interaction, verbal and non-verbal communication, and by restricted and repetitive behaviors. Diagnosis is solely based on behavioral analysis as biological markers and neurological underpinnings remain unknown. This makes the development of novel therapeutic strategies extremely difficult. 

As the cellular basis of autism spectrum disorders cannot be addressed in human patients, scientists have developed a number of mouse models for the disease. Similar to humans, mice are social animals and communicate through species-specific vocalizations. The mouse models harbor all diagnostic hallmark criteria of autism, such as repetitive, stereotypic behaviors and deficits in social interactions and communication.

Nadine Gogolla and her colleagues in the laboratory of Takao Hensch at Harvard University have now searched for common neural circuit alterations in mouse models of autism. They concentrated on the insular cortex, a brain structure that contributes to social, emotional and cognitive functions. ‘We wanted to know whether we can detect differences in the way the insular cortex processes information in healthy or autism-like mice’, says Nadine Gogolla, who was recently appointed Leader of a Research Group at the Max Planck Institute of Neurobiology.

As the researchers now report, the insular cortex of healthy mice integrates stimuli from different sensory modalities and reacts more strongly when two different stimuli are presented concomitantly (e.g. a sound and a touch). ‘We recognize a rose more easily when we smell and see it rather than when we just see or smell it’ says Nadine Gogolla. This capacity of combining sensory stimuli was consistently affected in all autism models the researchers looked at. Interestingly, often one sense alone elicited such a strong response that adding a second modality did not add further information. This is very reminiscent of the sensory hyper-responsiveness experienced by many autistic patients. The scientist further discovered that the insular cortex of adult autism-model mice resembled the activation patterns observed in very young control mice. ‘It seemed as if the insular cortex of the autism-models did not mature properly after birth’, says Gogolla.

For proper brain function, excitation and inhibition have to be in equilibrium. In the now identified part of the insular cortex, the scientists found that this equilibrium was disturbed. In one of the mouse models, inhibitory contacts between nerve cells were strongly reduced.

To test the influence of this reduction on sensory processing, the researchers gave mice the drug Diazepam, which is also known under the trade name Valium, to boost inhibitory transmission in the brain. Indeed, this treatment transiently rescued the capacity of the insular cortex to combine stimuli of different sensory modalities. The balance between excitation and inhibition in the brain is established after birth. The scientists thus treated young animals over several days with Diazepam. This treatment was efficient in reestablishing the insular cortex capacity for sensory integration permanently, even in adult mice that did not received any further treatment. Interestingly, also the stereotypic grooming of the animals was significantly reduced.

All autism models investigated showed alterations in inhibitory molecules. However, the alterations were very diverse. While in some models certain molecules were reduced, the opposite was true in another model. These results suggest that the disequilibrium between excitation and inhibition may be an important factor in the neuropathology of autism. However, future therapies will need to be carefully tailored to each particular subgroup of autism. For instance, an artificial boost of inhibition through a drug like Diazepam in healthy mice can throw the delicate equilibrium off and create changes in the insular cortex similar to those seen in the autism models. Whether a therapeutic strategy aimed on keeping the brain’s equilibrium between excitation and inhibition could be useful and if so, how to test the individuals’ status of the excitation/inhibition balance and how to implement individually tailored treatments, would need to be established through further studies and pre-clinical tests.