House of Mind

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

  • 14th September
    2014
  • 14
The brain is the organ of destiny. It holds within its humming mechanism secrets that will determine the future of the human race.
Wilder Penfield- The Second Career, 1963
  • 12th September
    2014
  • 12
The Curious Case of the Woman with No Cerebellum
Not sure how many of you have read about this by now, but it is such an amazing finding I decided to write about it (even though I retweeted this yesterday). 
This study is a clinical case report of a living patient with cerebellar   agenesis, an extremely rare condition characterized by the absence of the cerebellum. The cause is currently unknown, there are limited reported cases of complete cerebellar  agenesis, and most of what we know about the condition comes from autopsy reports instead of living patients. Moreover, the condition is difficult to study because most individuals with complete primary cerebellar agenesis are infants or children with severe mental impairment, epilepsy, hydrocephaly and other gross lesions of the CNS. The fact that this woman is alive and has a somewhat “normal” life is ground-breaking and presents a unique opportunity to study the condition.
The patient described in the study is 24 years old. She has mild mental impairment and moderate motor deficits. For example, she is unable to walk steadily and commonly experiences dizziness/nausea. She also has speech problems and cannot run or jump. However, she has no history of neurological disorders and even gave birth without any complications. 
Importantly, as shown above, CT  and MRI scans revealed no presence of recognizable cerebellar structures. Just look at that dark sport towards the back of the brain! In addition to these findings, magnetic resonance angiography also demonstrated vascular characteristics of this patient consistent with complete cerebellar agenesis- meaning that the arteries that normally supply this area were also absent bilaterally. How crazy is that? Futhermore, diffusion tensor imaging  indicated a complete lack of the efferent and afferent limbs of the cerebellum. 
Given that the cerebellum is responsible for both motor and non-motor functions, these results are pretty amazing. How can the brain compensate for such a heavy blow to its architecture and connectivity? According to the authors of the study: 

This surprising phenomenon supports the concept of extracerebellar motor system plasticity, especially cerebellum loss, occurring early in life. We conclude that the cerebellum is necessary for normal motor, language functional and mental development even in the presence of the functional compensation phenomenon.

Source:
Yu, F., Jiang, Q., Sun, X., and Zhang, R. (2014). A new case of complete primary cerebellar a genesis: clinical and imaging findings in a living patient. Brain. doi: 10.1093/brain/awu239

The Curious Case of the Woman with No Cerebellum

Not sure how many of you have read about this by now, but it is such an amazing finding I decided to write about it (even though I retweeted this yesterday). 

This study is a clinical case report of a living patient with cerebellar   agenesis, an extremely rare condition characterized by the absence of the cerebellum. The cause is currently unknown, there are limited reported cases of complete cerebellar  agenesis, and most of what we know about the condition comes from autopsy reports instead of living patients. Moreover, the condition is difficult to study because most individuals with complete primary cerebellar agenesis are infants or children with severe mental impairment, epilepsy, hydrocephaly and other gross lesions of the CNS. The fact that this woman is alive and has a somewhat “normal” life is ground-breaking and presents a unique opportunity to study the condition.

The patient described in the study is 24 years old. She has mild mental impairment and moderate motor deficits. For example, she is unable to walk steadily and commonly experiences dizziness/nausea. She also has speech problems and cannot run or jump. However, she has no history of neurological disorders and even gave birth without any complications. 

Importantly, as shown above, CT  and MRI scans revealed no presence of recognizable cerebellar structures. Just look at that dark sport towards the back of the brain! In addition to these findings, magnetic resonance angiography also demonstrated vascular characteristics of this patient consistent with complete cerebellar agenesis- meaning that the arteries that normally supply this area were also absent bilaterally. How crazy is that? Futhermore, diffusion tensor imaging  indicated a complete lack of the efferent and afferent limbs of the cerebellum. 

Given that the cerebellum is responsible for both motor and non-motor functions, these results are pretty amazing. How can the brain compensate for such a heavy blow to its architecture and connectivity? According to the authors of the study: 

This surprising phenomenon supports the concept of extracerebellar motor system plasticity, especially cerebellum loss, occurring early in life. We conclude that the cerebellum is necessary for normal motor, language functional and mental development even in the presence of the functional compensation phenomenon.

Source:

Yu, F., Jiang, Q., Sun, X., and Zhang, R. (2014). A new case of complete primary cerebellar a genesis: clinical and imaging findings in a living patient. Braindoi: 10.1093/brain/awu239

  • 11th September
    2014
  • 11

Neural Basis of Prejudice and Stereotyping

As social beings, humans have the capacity to make quick evaluations that allow for discernment of in-groups (us) and out-groups (them). However, these fast computations also set the stage for social categorizations, including prejudice and stereotyping.

According to David Amodio, author of the review I am summarizing: 

Social prejudices are scaffolded by basic-level neurocognitive structures, but their expression is guided by personal goals and normative expectations, played out in dyadic and intergroup settings; this is truly the human brain in vivo.

But what is the role of the brain in prejudice and stereotypes? First, let’s start by defining and distinguishing between the two: 

Prejudice refers to preconceptions — often negative — about groups or individuals based on their social, racial or ethnic affiliations whereas stereotypes are generalized characteristics ascribed to a social group, such as personal traits or circumstantial attributes. However, these two are rarely solo operators and are often work in combination to influence social behavior. 

Research on the neural basis of prejudice has placed emphasis on brain areas implicated in emotion and motivation. These include the amygdala, insula, striatum and regions of the prefrontal cortex (see top figure). Speficifically, the amygdala is involved in the rapid processing of social category cues, including racial groups, in terms of potential threat or reward. The striatum mediates approach-related instrumental responses while the insula, an area implicated in disgust, supports visceral and subjective emotional responses towards social ingroups or outgroups. Affect-driven judgements of social outgroup members rely on the orbital frontal cortex (OFC) and may be characterized by reduced activity in the ventral medial prefrontal cortex (mPFC), a region involved in empathy and mentalizing. Together, these structures are thought to form a core network that underlies the experience and expression of prejudice. 

In contrast to prejudice, which reflects an evaluative or emotional component of social bias, stereotypes represent the cognitive component. As such, stereotyping is a little more complex because it involves the encoding and storage of stereotype concepts, the selection and activation of these concepts into working memory and their application in judgements and behaviors. When it comes to social judgments, I find it useful to think of prejudice as a low road, and stereotypes as a high road (which recruits higher order cortical areas). For example, stereotyping involves cortical structures supporting more general forms of semantic memory, object memory, retrieval and conceptual activation, such as the temporal lobes and inferior frontal gyrus (IFG), as well as regions that are involved in impression formation, like the mPFC (see bottom figure).

Importantly, although prejudice and stereotyping share an overlapping neural circuitry, they are considered as different and dissociable networks. Also, it is important to remember that areas such as the mPFC, include many subdivisions that may contribute to different aspects of the network. This is important because these within structure subdivisions are usually not readily identifiable in neuroimaging studies. Anyway, if you want to learn more about the specifics of these network and obtain real world examples of these networks at work, read the full review article (see below). 

Source:

Amodio, D.  (2014). The neuroscience of prejudice and stereotyping. Nature Reviews Neurociencedoi: 10.1038/nrn3800

  • 5th September
    2014
  • 05
How to Become a Neuroscientist

Recently, I have been flooded with questions regarding grad school, the PhD track and other matters so I decided to update this post from 3 years ago. I have expanded on some sections that I know more about now. 

houseofmind:

I have gotten so many questions about people who are interested in neuroscience as a career that I have created this post so I can reference back to it in the future.

Note: This is a guide directed towards people that want RESEARCH careers. My graduate program’s approach towards neuroscience  integrated knowledge from many areas like electrophysiology, cellular and molecular biology, and computational neurobiology relying on mathematics/physics. Also, a number of you seem to be under the impression that I am studying neuropsych, which I am not. Neuropsych is traditionally a more clinically-oriented branch within neuroscience. 

First of all, if you want to become a neuroscientist, you will most likely have to complete formal graduate training in a related branch or field. You have to be ready for this, because it is something that will take a long time. Not to worry though, time flies and if you like what you’re doing you won’t mind…

In college, the most common options are majoring in either biology or psychology. Some schools have a neuroscience or biopsychology major that may be in the biological sciences department or the psych department or even a combination of both. For example, you could major in biology and minor in psych or vice versa… Because neuroscience is an interdisciplinary field, I would recommend taking courses outside your major (especially if you’re in a psych dept). Helpful and attractive courses include: physics, calculus, organic chemistry, biochem, genetics, cell and molecular biology, bioethics, and neuropsych/psych courses. Importantly, some people come from other backgrounds like electrical/computer engineering that are also helpful in areas like electrophysiology, computational neurobiology and neuronal modeling. Thus, a major in biology or psychology is not a MUST but it definitely gives you an advantage. 

While in college, it is also important to gain research experience (try volunteering in labs just to learn or for course credit) while maintaining a decent GPA. And by decent I mean higher than 3.5 on a 4.0 scale. Of course, not all is lost if your GPA is below a 3.5. It will just be a little harder as you might not be regarded as competitive as other students. You can make up for this with research experience. Mind you, if you have a 4.0 but all your classes are in the soft sciences and you didn’t take challenging courses, you’re in trouble as well… Third year of college (assuming you will graduate in 4 years) is crucial. This is the time to beef up your CV/resume, take the GRE, talk to people who will be your references, and complete your application to graduate schools. Graduate schools have a wide variety of programs (i.e. neurobiology, neuroscience, neuropsych) with different kinds of focus. Look at the curriculum for each program and find one that is well-suited for your interests and career aspirations. Remember to apply early and to ask for fee waivers, if available (I applied to 8 schools and got fee waivers for all but one of them!). Your personal statement is essential. And by that I mean it absolutely has to be great. Different schools have different criteria for this essay and you should remember to pay attention to these criteria and follow instructions. You should also have several people proofread it before you send it. Do not skip this part, as any proofreaders will likely catch mistakes that are invisible to you- no joke.

After you submit your application, send an e-mail to make sure everything is complete. If you get an interview, ask who your interviewers will be and familiarize yourself with their research and areas of expertise. Be nice, enthusiastic and ask smart questions. Also, during your interview, highlight why you want to be part of the training environment at that particular university or location and why you’d be a good match for the program and the department. If you are interested in conducting your doctoral work with a faculty member that you’re interviewing with, ask about funding and the possibility of rotating in the lab. For example, I interviewed with a faculty member that interested me, but I found out during interviews that he could not take me because of funding- even if the rotation went well. Also, this should go without saying but remember to be cordial to students that you meet and other interviews. Finally, remember to send thank you e-mail to the faculty that met with you and anybody else you deem appropriate to thank. 

Graduate school: Do your best to learn and understand the material presented in your intro classes, as it will be the foundation that most of the other classes will be built upon but don’t worry about learning EVERYTHING. You will find that you will learn what you need most as you go along- acquiring knowledge is a process. You don’t need stellar grades in graduate school, but you do need to pass, which for most universities is a solid B. While you are during your first year, you will most probably rotate through different labs in which you will be able to get to know the lab, learn the techniques and figure out if it’s a good fit for you. After you finish classes, you will be working towards your thesis proposal. This is the meat of grad school. Work, work, work. Most likely, you will need to propose your thesis, select a review committee (composed of experts in fields relating to your research), work in lab and collect data to support your thesis, and defend it. Be savvy about your committee choices because once you propose, many programs will not let you switch members unless something our of the ordinary happens. This being said, pick faculty members that you have a good relationship with (or are interested in developing a good relationship with), but that are thoughtful and critical of your work.  Hold committee meetings regularly (once or twice a year). Get that thesis out, present at scientific conferences, and publish well.  Bonus if you learn how to write grants. Your committee will tell you when you are ready to graduate, although this is often a conversation involving your committee, yourself, and the PI. After you defend your thesis, your committee decides your fate. 

Post-graduate school: Postdoctoral fellowships are a common way of learning additional techniques or addressing a different but related question. Or you could also go into something you don’t know much about. I keep hearing that a postdoc is supposed to add versatility, diversity and publications to your CV. This is also the time period in which you learn how to run a lab, work on your own independent projects, write grants, and decide where you want your career to go (i.e. industry, academia, clinical). Think about it as an extension of your training in which you get more freedom and flexibility. Start looking for postdoctoral positions early (up to a year in advance). Talk to your PI, other PIs, and your network (you should have one by the end of your PhD) about possible opportunities. You can also look for T32 programs, which include a limited period of funding and other perks. 

Alternatively, some people enroll in medical school to pursue an MD degree in addition to the Ph.D. one while others go back to school for other degrees (ex. PsyD, law, etc…). Others find industry jobs or go into public policy. 

Hope this helps. Good luck to-be PhDs!

  • 4th September
    2014
  • 04
So I'm a second year masters student in physiology and my research is in neuroendocrinology. I keep getting told not to go for my phd and just get out with a masters and go into industry. The job outlook for those with a phd I heard was very bleak and they tend to value a diverse masters degree than a narrowed phd degree and they don't want to pay a higher salary to someone with a doctorate. I am at a loss at what to do...what do you think?

Asked by: artisticneuron

The job outlook in academia is indeed tough (too many PhDs for a limited number of tenure-track positions), but not impossible. Industry is very competitive as well and the job is not guaranteed, so there’s that to think about… I guess your choice depends on what you want and what your priorities are. Do you know what type of career do you want?

If you do choose to go into industry, you will likely be worth more if you have a PhD. I actually have classmates (aka other PhD students) that were working in industry before and decided to go back to school for a PhD so that they could make more money and be appointed to leadership positions within the company. I know someone with a PhD that recently got hired in industry and he is now running the electrophysiology core and making twice as much as postdocs make. They didn’t seem to mind that they had to spend more on him… Maybe it’s on a case by case basis?

  • 27th August
    2014
  • 27
Histamine 
….And the transmitter series is back in business. If you’ve been following from the start, you know what I’m talking about ;) If you’re new, welcome!
Here is a list of neurotransmitters that have been covered so far: 
Dopamine
Serotonin
Norepinephrine
Glutamate
GABA
Acetylcholine
Histamine acts as a modulatory neurotransmitter. As such, it acts through G-protein coupled receptors to fine-tune excitatory and inhibitory neurotransmitters.  Histamine is involved in a number of biological processes, including immune and inflammatory responses, maintenance of wakefulness, feeding and energy balance and regulating physiological function in the gut. 
Histamine is produced in the brain by mast cells and neurons for regulated release. In the adult mammalian brain, histamine is produced exclusively in the tuberomammillary nucleus (TMN) of the hypothalamus, which sends fibre projections to all  major parts of the brain. Histamine released from TMN neurons activate 3 G-protein coupled receptors. These are:
H1Rs and H2Rs- located in neuronal and glial cells, expressed postsynaptically and have important roles in the cerebral cortex, striatum, hypothalamus, and hippocampusH3Rs- exclusively expressed in neurons; can act as both auto receptors in histaminergic neurons and heteroreceptors in nonhistaminergic neurons which regulate release of other neurotransmitters


Studies in humans and animal models of psychiatric disorders suggest a role for histamine dysfunction in the following diseases:
Narcolepsy and sleep disordersCognitive dysfunction and Alzheimer’s diseaseMotor disorders such as Parkinson’s disease and Gilles de la Tourette syndromeSchizophreniaAddictive behaviorsMultiple sclerosis 
Sources: 
Panula and Nuutinen (2013). The histaminergic network in the brain: basic organization and role in disease. Nature Reviews Neuroscience 14: 472-487. 

Histamine 

….And the transmitter series is back in business. If you’ve been following from the start, you know what I’m talking about ;) If you’re new, welcome!

Here is a list of neurotransmitters that have been covered so far: 

Dopamine

Serotonin

Norepinephrine

Glutamate

GABA

Acetylcholine

Histamine acts as a modulatory neurotransmitter. As such, it acts through G-protein coupled receptors to fine-tune excitatory and inhibitory neurotransmitters.  Histamine is involved in a number of biological processes, including immune and inflammatory responses, maintenance of wakefulness, feeding and energy balance and regulating physiological function in the gut. 

Histamine is produced in the brain by mast cells and neurons for regulated release. In the adult mammalian brain, histamine is produced exclusively in the tuberomammillary nucleus (TMN) of the hypothalamus, which sends fibre projections to all  major parts of the brain. Histamine released from TMN neurons activate 3 G-protein coupled receptors. These are:

H1Rs and H2Rs- located in neuronal and glial cells, expressed postsynaptically and have important roles in the cerebral cortex, striatum, hypothalamus, and hippocampus
H3Rs- exclusively expressed in neurons; can act as both auto receptors in histaminergic neurons and heteroreceptors in nonhistaminergic neurons which regulate release of other neurotransmitters

Studies in humans and animal models of psychiatric disorders suggest a role for histamine dysfunction in the following diseases:

Narcolepsy and sleep disorders
Cognitive dysfunction and Alzheimer’s disease
Motor disorders such as Parkinson’s disease and Gilles de la Tourette syndrome
Schizophrenia
Addictive behaviors
Multiple sclerosis 

Sources: 

Panula and Nuutinen (2013). The histaminergic network in the brain: basic organization and role in disease. Nature Reviews Neuroscience 14: 472-487.