House of Mind

"Biology gives you a brain. Life turns it into a mind" - Jeffrey Eugenides

  • 1st June
    2012
  • 01
My first publication (click to see full article)

The day has finally come- I’m finally published and second author on a publication! Most of this work was done as part of my rotation project during my first year in graduate school. These findings (particularly the social behavior data) were my intellectual and technical contribution to the project and they laid the foundation for the NSF GRFP that I wrote in 2010 and was awarded in 2011. I’m extremely happy and proud to be able to share my personal line of research with all of you and I’d love to hear your questions/comments. Thanks for following and go click on the link above to read the full article!

Effects of Early-Life Abuse Differ across Development: Infant Social Behavior Deficits Are Followed by Adolescent Depressive-Like Behaviors Mediated by the Amygdala.

Raineki C, Cortés MR, Belnoue L, Sullivan RM.

Emotional Brain Institute, Nathan Kline Institute, Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, Orangeburg, New York 10962.

Abuse during early life, especially from the caregiver, increases vulnerability to develop later-life psychopathologies such as depression. Although signs of depression are typically not expressed until later life, signs of dysfunctional social behavior have been found earlier. How infant abuse alters the trajectory of brain development to produce pathways to pathology is not completely understood. Here we address this question using two different but complementary rat models of early-life abuse from postnatal day 8 (P8) to P12: a naturalistic paradigm, where the mother is provided with insufficient bedding for nest building; and a more controlled paradigm, where infants undergo olfactory classical conditioning. Amygdala neural assessment (c-Fos), as well as social behavior and forced swim tests were performed at preweaning (P20) and adolescence (P45). Our results show that both models of early-life abuse induce deficits in social behavior, even during the preweaning period; however, depressive-like behaviors were observed only during adolescence. Adolescent depressive-like behavior corresponds with an increase in amygdala neural activity in response to forced swim test. A causal relationship between the amygdala and depressive-like behavior was suggested through amygdala temporary deactivation (muscimol infusions), which rescued the depressive-like behavior in the forced swim test. Our results indicate that social behavior deficits in infancy could serve as an early marker for later psychopathology. Moreover, the implication of the amygdala in the ontogeny of depressive-like behaviors in infant abused animals is an important step toward understanding the underlying mechanisms of later-life mental disease associated with early-life abuse.

  • 27th September
    2011
  • 27

This is your brain on stress and city living

Although city life offers many advantages and even some health benefits, meta-analyses indicate that city living is a substantial risk factor for mood and anxiety disorders. Basically, people who live in cities have a higher incidence for these disorders. Also, genetically predisposed individuals are at an even greater risk if they are brought up in cities. In schizophrenia, for example, the incidence is nearly doubled in subjects that were born, raised and currently lived in the city. And let’s not forget that, usually, with city life comes a more stressful social environment, a factor known to exacerbate many psychiatric disorders, particularly the ones mentioned above. 

So how is it that being from/living in a certain place can affect how your brain works? 

In order to understand this question, Lederborgen et al (2011) used functional magnetic resonance imaging (fMRI) to study the neural responses of subjects taking a social stressor task that consisted of solving math problems under time pressure while also receiving negative feedback from the experimenter. The subjects differed in terms of their living conditions, as they were from urban (+100,000 people), town (+10,000) or rural areas.

The task was an effective stressor as it successfully induced stress, indexed by increases in heart rate, blood pressure, and salivary cortisol (stress hormone) levels. In addition, there was significant activity in brain areas implicated in the stress response, emotion, and social behavior. Of these, 2 major areas exhibited the most robust changes: 

  • Amygdala: Current city living was associated with increased amygdala activity. Activation positively correlated with the size of the city that the individual currently lived in, with city dwellers having the highest levels of amygdala activation.
  • Anterior cingulate cortex: Activation correlated with the upbringing (or how long) a person had lived in a city. Individuals that were entirely brought up in cities showed the greatest perigenual anterior cingulate cortex (pACC) activation. This region is important due to its role in the regulation of amygdala activity during negative affect and stress. 

Moreover, the authors show evidence suggesting that there is reduced functional connectivity between the amygdala and specifically, the perigenual anterior cingulate cortex of those participants that were born and raised in cities. Considering that weakened coupling of these areas has also been linked to genetic risk for psychiatric disorders, these findings have important clinical relevance. Now let’s stretch our thinking- with urbanization increasingly becoming the way of life and the very real risk of overcrowding, what does this mean for brain development?

The authors state that the results were not explained by demographic/clinical factors or a number of other variables. They have also been able to replicate their findings in a larger and better distributed sample. However, they recognize that limitations of their work include that their study was purely correlational and they discuss the need for a larger scale study that has ways of identifying and measuring more variables that may be related to city living. 

For those of you that live (or were brought up) in cities, cheer up. There are a variety of reasons for choosing to live (and enjoy) the city life. In a way, the city has its way of forcing you into developing coping strategies- which is a good thing, right? Now here’s something to think about: psychologists have even found that one of the factors accounting for the preference of city living is the degree of control that people have (and feel they have) over their lives. 

Sources: 

Kennedy, DP & Adolphs R. 2011. Stress and the city. Comment on: Nature. 474: 452-3. doi: 10.1038/474452a

Lederborgen et al. 2011. City living and urban upbringing affect neural social stress processing in humans. Nature. 474: 498-500. oi: 10.1038/nature10190

  • 31st May
    2011
  • 31
Amygdala volume correlates with the size and complexity of social networks in humans Evolutionarily, one of the most important social challenges is to be able to distinguish between friend and foe, which can aid in survival. The social brain hypothesis, which suggests that living in larger and complex social groups selected for larger brain regions capable of performing relevant computations. One of these brain regions is the amygdala, a critical structure for learning, memory and emotion that has been implicated in mood disorders, social behavior, and interpersonal relationships (i.e. mother-infant interactions). Because of its central functional role and anatomical position, the authors proposed that amygdala volume should be associated with size of social network (size is typically considered an indicator of processing capacity. Moreover, neuroimaging studies done in nonhuman primates have supported this association between an enlarged amygdala and larger social groups.Thus, there is a notion that a larger amygdala volume enables increased processing of social demands that form part of life in a social group or hierarchy. In a 2011 study, Bickart et al. examined whether amygdala volume varies as a function of individual variation in the size and complexity of social groups within humans. The group examined the social networks, the number of people that the individual maintains or “regular contacts” (also an indication of overall network size), in approximately 58 healthy adults (healthy= absence of DSM-IV diagnoses). The group also employed another social scale to measure the number of different groups that the contacts belonged to, reflecting network complexity. Furthermore, the performed quantitative morphometric analyses of MRI data. According to Bickart, linear regression analyses revealed that subjects with larger and more complex social networks had larger amygdala volume (even when controlling for variables such as age) with no lateralization of effect. The group found no significant differences in other non-social brain structures like the hippocampus and other subcortical structures.  Sources: Bickart, et al. (2011). Amygdala volume and social network size in humans. Nature Neuroscience. 14:163-164. doi:10.1038/nn.2724 Image: http://www.nature.com.ezproxy.med.nyu.edu/neuro/journal/v14/n2/fig_tab/nn.2724_F1.html

Amygdala volume correlates with the size and complexity of social networks in humans

Evolutionarily, one of the most important social challenges is to be able to distinguish between friend and foe, which can aid in survival. The social brain hypothesis, which suggests that living in larger and complex social groups selected for larger brain regions capable of performing relevant computations. One of these brain regions is the amygdala, a critical structure for learning, memory and emotion that has been implicated in mood disorders, social behavior, and interpersonal relationships (i.e. mother-infant interactions). Because of its central functional role and anatomical position, the authors proposed that amygdala volume should be associated with size of social network (size is typically considered an indicator of processing capacity. Moreover, neuroimaging studies done in nonhuman primates have supported this association between an enlarged amygdala and larger social groups.Thus, there is a notion that a larger amygdala volume enables increased processing of social demands that form part of life in a social group or hierarchy.

In a 2011 study, Bickart et al. examined whether amygdala volume varies as a function of individual variation in the size and complexity of social groups within humans. The group examined the social networks, the number of people that the individual maintains or “regular contacts” (also an indication of overall network size), in approximately 58 healthy adults (healthy= absence of DSM-IV diagnoses). The group also employed another social scale to measure the number of different groups that the contacts belonged to, reflecting network complexity. Furthermore, the performed quantitative morphometric analyses of MRI data. According to Bickart, linear regression analyses revealed that subjects with larger and more complex social networks had larger amygdala volume (even when controlling for variables such as age) with no lateralization of effect. The group found no significant differences in other non-social brain structures like the hippocampus and other subcortical structures. 

Sources:

Bickart, et al. (2011). Amygdala volume and social network size in humans. Nature Neuroscience. 14:163-164. doi:10.1038/nn.2724

Image: http://www.nature.com.ezproxy.med.nyu.edu/neuro/journal/v14/n2/fig_tab/nn.2724_F1.html

  • 15th November
    2010
  • 15

PKMZ and CREB’s Role in in Memory Formation and Retention (Wiedenmayer)

PKMZ activity promotes early life traumatic memory formation and retention.

CREB (cAMP response element binding) is a protein that is also a transcription factor and is used as a neuronal marker to identify candidate brain areas involved in fear memory formation. It’s active form, phosphorylated CREB (pCREB) regulates protein synthesis necessary for synaptic strengthening during learning. 

PKMZ is a persistently active, memory-related protein kinase (transfers phosphate group) involved in late phase long-term potentiation (or synaptic strengthening). It has been demonstrated to be required for contextual fear memories in the amygdala but not in the hippocampus. 

Immediate increase in CREB activity in both the hippocampus and the amygdala, along with PKMZ activity in the amygdala after reconsolidation of fear memories play critical roles in fear learning and long-term memory maintenance. 

Recently, I’ve become more interested in PKMZ because of its multiple roles, including addiction and cue-related memories… Stopped by this poster at SfN and learned that it ties into my current research as well.

  • 15th November
    2010
  • 15

So today I learned…

1. Identification of an astrocyte-secreted protein that is sufficient to induce fully functional synapse formation (Allen): Glypican4 is sufficient and necessary for enhancing post-synaptic activity between retinal ganglion cells: it increases surface levels of the GluR1 subunit of AMPA receptors (AMPA receptors being metabotropic glutamate receptors). 

2. Retrieval of context-drug memories increases the number of recently activated synapses in the basolateral amygdala (Rademacher): Learning to associate context with drugs “re-wires” the basolateral amygdala (BLA) to form context-drug associations by increasing the number of excitatory and inhibitory synapses. Arc is a useful protein that provides a map of recently activated synapses following retrieval of implicit long term memory.