Neuroscience: Default Mode Network

From yee Wiki: In neuroscience, the default mode network (DMN), also default network, or default state network, is a large scale brain network of interacting brain regions known to have activity highly correlated with each other and distinct from other networks in the brain.

The default mode network is most commonly shown to be active when a person is not focused on the outside world and the brain is at wakeful rest, such as during daydreaming and mind-wandering. But it is also active when the individual is thinking about others, thinking about themselves, remembering the past, and planning for the future. The network activates "by default" when a person is not involved in a task. Though the DMN was originally noticed to be deactivated in certain goal-oriented tasks and is sometimes referred to as the task-negative network,mit can be active in other goal-oriented tasks such as social working memory or autobiographical tasks.The DMN has been shown to be negatively correlated with other networks in the brain such as attention networks.

Evidence has pointed to disruptions in the DMN of people with Alzheimer's and autism spectrum.

The default mode network is known to be involved in many seemingly different functions:

It is the neurological basis for the self:

Autobiographical information: Memories of collection of events and facts about one's self

Self-reference: Referring to traits and descriptions of one's self

Emotion of one's self: Reflecting about one's own emotional state

Thinking about others:

Theory of Mind: Thinking about the thoughts of others and what they might or might not know

Emotions of other: Understanding the emotions of other people and empathizing with their feelings

Moral reasoning: Determining just and unjust result of an action

Social evaluations: Good-bad attitude judgments about social concepts

Social evaluations: Good-bad attitude judgments about social concepts

Social categories: Reflecting on important social characteristics and status of a group

Remembering the past and thinking about the future:

Remembering the past: Recalling events that happened in the past

Imagining the future: Envisioning events that might happen in the future

Episodic memory: Detailed memory related to specific events in time

Story comprehension: Understanding and remembering a narrative

The default mode network is active during passive rest and mind-wandering. Mind-wandering usually involves thinking about others, thinking about one's self, remembering the past, and envisioning the future.

Electrocorticography studies (which involve placing electrodes on the surface of a subject's scalp) have shown the default mode network becomes activated within a fraction of a second after participants finish a task.

Studies have shown that when people watch a movie, listen to a story, or read a story, their DMNs are highly correlated with each other. DMNs are not correlated if the stories are scrambled or are in a language the person does not understand, suggesting that the network is highly involved in the comprehension and the subsequent memory formation of that story. The DMN is shown to even be correlated if the same story is presented to different people in different languages, further suggesting the DMN is truly involved in the comprehension aspect of the story and not the auditory or language aspect.

The default mode network has shown to deactivate during external goal-oriented tasks such as visual attention or cognitive working memory tasks, thus leading some researchers to label the network as the task-negative network. However, when the tasks are external goal-oriented tasks that are known to be a role of the DMN, such as social working memory or an autobiographical task, the DMN is positively activated with the task and correlates with other networks such as the network involved in executive function.

A hitherto unsuspected possibility is that the default network is activated by the immobilization inherent in the testing procedure (the patient is strapped supine on a stretcher and inserted by a narrow tunnel into a massive metallic structure). This procedure creates a sense of entrapment and, not surprisingly, the most commonly reported side-effect is claustrophobia. This alternative view is suggested by a recent article that links theory of mind to immobilization.

Ooooooooo Brain Scans

A look at The Simpsons' Comic Book Guy's brain.

Brain Circuits and Addiction

What is the nature of addiction?

Amy Winehouse was a terrific talent and one of the favorite recording artists of all time. She also struggled with substance abuse. To what extent remains largely unknown but her death has fueled debate as to the precise nature of drug addiction and how it should be addressed by society as a whole.

In other words, why do some people behave in the often self-destructive manner in which they do? And why are people addicted to drugs in the first place?  How, if at all, might they be helped?

Now, you might think that this is a spectacularly hard task to delve into the neuroscience of addiction try to shed some light. Surely, drugs of abuse (such as amphetamines, cocaine, opiates, alcohol and nicotine) have a broad range of actions that are wholly dissimilar from each other? Well, that is partly true, but when it comes to their addictive properties, they have more in common than you might think.

What constitutes addiction?

Addiction, as most will know, develops as a result of chronic exposure to a particular substance. People who are addicted to a drug show similar patterns of behaviour. These include:

1. A compulsion to seek the drug

2. An inability to control the amount of drug consumption

3. A negative emotional state when subjected to periods of withdrawal

Neuroscientists have sought to understand the neural mechanisms underlying these behaviours for generations and emerging from these studies is the concept of the ‘reward circuit’ that seems to be involved in the development and maintenance of drug addiction.  In fact, research on the medial forebrain pleasure circuit may be entering a golden age of discovery.

Now, a lot of neuroscience (indeed any science) is about gradually building up a picture from fragments of information. In most cases, that information may not even come from human subjects but from animal models. That means that current ideas regarding drug addiction are far from unequivocal, but from looking at the correlations between how the rodent brain and human brain are altered during the development of drug addiction, we can make careful assumptions about what might be the general rule.
You see, the brain behaves a little bit like a factory, with different departments responsible for producing a certain sort of feeling or behaviour. This means that there are anatomically distinct areas that are concerned with happiness, memory, movement and so on. This is (as ever) an oversimplification, as it is usually the concerted action of several brain regions that lead to emergence of a particular thought or action. However, it is useful to think of the brain in this way, particularly when analysing how brain circuits are altered in drug users.

The reward circuit

The reward circuit consists of several brain regions that are heavily interconnected; each with distinct – but related – functionality. These include the nucleus accumbens (a brain region that is extremely well documented for its involvement in drug addiction), the ventral tegmental area, the amygdala, the prefrontal cortex, the hippocampus and the insula, among others.

Dysfunction in each of these areas has been implicated in the onset and maintenance of drug-addiction, each area being responsible for a slightly different facet of the drug-addicted mental state.

The nucleus accumbens: pleasure

Now, the nucleus accumbens is known as the reward center of the brain. Largely because in various different experimental paradigms, subjects that report that they are experiencing reward show increased activity in this area. This can be whilst taking drugs of abuse or simply eating, engaging in sexual activity or indeed anything associated with pleasurable reward.

All drugs of abuse raise the level of a chemical known as dopamine in the nucleus accumbens and it is this elevation in dopamine (initiated in different ways by different drugs) that is responsible for the feeling of euphoria associated with drug intake.

However, persistent activation of the nucleus accumbens leads to the development of drug addiction, primarily due to persistent changes in the level of dopamine, which leads to an alteration in how people respond to otherwise rewarding stimuli. Put simply, after disruption of the dopamine levels in the nucleus accumbens, people get less satisfied with things that aren’t their drugs of choice. Furthermore, people derive progressively more pleasure from the drug in question, exacerbating the effect.

The amygdala: fear

On the flip side of the coin, the amygdala is a region of the brain situated right next to the nucleus accumbens but is often associated with feelings of fear and anxiety.
As opposed to the positive reinforcement created by the nucleus accumbens, it is during withdrawal that the amygdala seems to have its largest role. Basically, as access to the drug is taken away, stress-related hormones are increased in the amygdala which can lead (at least partially) to the negative feeling associated with withdrawal.

The hippocampus: memory

The hippocampus is an area of the brain that is associated with learning and memory as well as the ability to perform tasks requiring spatial navigation, such as finding your way around a building. It is also important for ‘contextual-conditioning’, meaning that it enables the mind to establish links between an environmental cue (a nightclub, for example) and a memory (such as taking a drug.)

Activation of the hippocampus is implicated in initiating cue-induced drug-seeking behaviour. Indeed, it has been shown that cue-induced craving of drugs (eg. the feeling of needing a drink in a pub or a cigarette with a cup of coffee) is associated with an increase in activity in the hippocampus (as well as the amygdala) in humans, indicating that normal memory function may be being encroached upon by drugs of abuse.

The prefrontal cortex: decision

The prefrontal cortex consists of several subdivisions including the orbitofrontal cortex and dorsolateral prefrontal cortex. These areas have a variety of different functions but are often described as being imperative in carrying out decision-making processes in response to internal/external-cues, a process known as executive function.

It is believed that the activity of the prefrontal cortex is disrupted in subjects who are addicted to drugs. This may go some way to explaining why drug users often make poor decisions regarding drug intake (ie. pursuing a drug whilst fully aware of the negative impact drug intake will have on them and the people around them.)

What goes on in the brain of a drug addict

So…
As complicated as that may have sounded, it represents a gross oversimplification of what actually goes on in the mind of a drug addict. I simply wanted to introduce you to some of the concepts that are emerging as a result of neuroscientific research and give you a flavor of what is to come in future posts. As I move through my journey into drug addiction, I will make constant references to the reward circuit and its components and so an introduction was necessary to familiarise you with the brain’s machinery. -- Dr. Paul

Dr. Paul is a graduate from the University of Bristol and the author of Dr Paul’s Brain Talk, a neuroscience-related magazine. Dr. Paul believes that over the coming decades, neuroscience research will begin to have a greater impact on our lives and he aims to bring the findings of this fascinating field to the general public, in words they can understand.

Whole-Brain Circuit Map

Mapping the mammalian brain circuits

Thirty-seven researchers from Cold Spring Harbor Laboratory (CSHL) and 20 other major research institutions in the U.S. and Europe have issued a major challenge to the neuroscience community. At long last, the time has come, they argue in a just-published paper, to assemble a comprehensive map of the major neural circuits in the mammalian brain.

In an age in which the genomes of a number of organisms, including that of humans, have been fully sequenced and can be accessed instantly by anyone with a computer, anywhere in the world, it is astonishing to consider that "we have, as yet, not been able to compile a whole-brain map of the circuitry that underlies the functioning of our own brains," notes Professor Partha P. Mitra, Ph.D., senior author of the paper and leader of the ongoing Brain Architecture Project at CSHL, funded by the WM Keck Foundation. To help address this knowledge gap, Mitra organized a series of meetings at the CSHL Banbury Center in 2007 and 2008, from which this proposal grew.

The neuroscience community's "sparse knowledge" of mammalian neuroanatomical circuitry is "perhaps the largest lacuna in our knowledge about nervous system structure," Mitra and his colleagues observe in their paper, which appears in the recent issue of PLoS Computational Biology

Map the brain circuits of the mouse.

The case for committing resources to assembly of a whole-brain circuit map is especially strong, they say, because it almost certainly will provide insights about what goes wrong in brain dysfunctions spanning a range of neurodevelopmental illnesses including autism, schizophrenia, and perhaps mood disorders such as depression, bipolar illness, and obsessive-compulsive disorder (OCD). Further, the authors argue that technological advances along with decreasing computational and data-storage costs have made such an effort feasible now, when it could only be dreamt of even in the recent past.

A community-wide project to prepare a 'first draft'.
Mitra and his co-authors therefore advocate for "a concerted effort" to complete a first-draft circuit map of the entire mouse brain within two to three years, as a first step to mapping vertebrate brain architecture across species. The proposed project would ideally be pursued simultaneously by neuroresearchers at multiple institutions as per standardized protocols. "In this respect," says Jason Bohland, Ph.D., a postdoctoral neuroscience researcher at CSHL and the paper's main author, "it would be analogous to the multi-institution effort to sequence the human genome, with the important distinction that our brain-circuit map could be completed much more rapidly and would cost a small fraction of the genome project as little as a few million dollars ranging up to perhaps $20 million, depending on the redundancy in coverage that we commit to." 

To date, research on the brains of mammals typically, rodents and non-human primates has described, using a multitude of different techniques, only a small fraction of the total set of neuronal pathways, in an unsystematic manner. Even though spectacular advances have been made in neuroscientists' ability to examine and measure the output of individual neurons in the brains of living animals, such studies have shed little light on how the brain as a whole is wired together. In much the same way that the study of the genome has shifted to emphasize networks of interacting genes, neuroresearchers are beginning to understand the importance of circuit-level properties in the normal and dysfunctional brain.

This, says Mitra, is notable in part because "the defining architectural feature of the nervous system is precisely that it forms a circuit." One critical question, therefore, is at what level of resolution to attempt a whole-brain circuit diagram. Mitra and co-authors are proposing to map the circuit in the mouse brain at what they call a "mesoscopic scale." Somewhere between the micro- and macroscopic, this intermediate level corresponds with the basic architectural organization of the mouse brain, in terms of its observed cellular, chemical, and genetic makeup. Most importantly, the authors expect this to be the level at which the pattern of connections in individual animals will have a significant degree of commonality, ultimately providing a meaningful and tractable description of the brain's structure.

Tracing the inputs and outputs of each area. Brain organization at the macroscopic level the level of entire structural-functional systems and major nerve-fiber bundles is somewhat understood, but provides an insufficient level of description of the overall wiring diagram. Some researchers have argued that it would be best to map mouse brain structure at the micro-level of individual synapses the myriad gaps across which individual neurons communicate, with the help of neurotransmitters and modulators such as glutamate, GABA, acetylcholine, dopamine and serotonin. But this isn't technologically feasible to do on a brain-wide scale for a mouse, let alone larger vertebrate brains. Data storage at such a scale, which would involve storing nanometer-resolution images made with electron microscopes, could cost as much as one billion dollars, Mitra says.

In contrast, the proposed project is "both technologically and economically practical, involving techniques that are well proven," as per Mitra. All measurements will be made in standard lab mice of precisely the same developmental age 56 days, as in the Allen Brain Atlas project; each mouse will be injected in one brain area with one or more tracers, which are actively transported within individual nerve cells. These tracers appears to be "conventional" molecules that have been used by neuroanatomists over the last several decades, or engineered viruses that infect cells at the injection site, marking their extent through the expression of a fluorescent protein. The utility of these techniques is in tracing projection neurons either from axon terminals to potentially distant cell bodies or vice-versa.

Together, the tracers will provide a view of the pattern of inputs and outputs for a given site in the brain. These patterns will be mapped from images of thinly sectioned brain slices obtained using light microscopy, taking advantage of recently available technologies to rapidly and automatically scan and digitize a set of slides.

Extracting and combining the results across individual mice will be a computational challenge that requires automating a number of of the steps that neuroanatomists now perform by hand. Bohland is aware of these challenges. "Solving these problems in general is difficult because the circumstances of individual experiments can be wildly different," he acknowledges, "But in the systematic, standardized protocols we call for, finding solutions becomes considerably easier." .

The full dataset will comprise hundreds of terabytes a very modest data-storage burden, as per Mitra. "That will give us about twofold coverage of the entire brain circuit in a first draft, and could be accomplished in two or three years, with cooperation from the neuroscience community. At more robust funding levels, we could attempt 10-fold coverage over, perhaps, a five-year period." In the spirit of genome projects, all data from the proposed program would be made rapidly available over the web to the entire research community.

While the immediate focus now is to bring a mouse connectivity project to fruition, the authors also make the case for cataloging and digitizing results from existing studies in other species, and for filling key gaps with targeted studies. Moreover, there is an important need, they argue, for further development and validation of experimental techniques that can be used directly in the human brain.

Comparing circuits in healthy brain vs. the brain in autism or schizophrenia. Perhaps the most exciting aspect of such a brain mapping project is its likelihood to deepen our understanding of what goes awry at the circuit level in neuropsychiatric illnesses. At present, researchers are lacking data of this type with which to work on theories of disease causation and mechanism. "In recent years," Mitra observes, "a number of researchers have made mouse models of various complex disorders, such as schizophrenia or autism. But so far no one has been able to pinpoint what goes wrong in brain circuitry when you have one of these devastating illnesses.
"It has been hypothesized, at least for neurodevelopmental disorders, that the circuit is altered during the developmental process, in some manner fundamentally changing the circuit. Once we have succeeded in fully mapping the brain in the healthy mouse, we will be able to measure, objectively, how the whole-brain circuit differs in mice that model various aspects of behaviors or known genetic alterations linked to human illnesses like autism or schizophrenia. "I think this would be a crucial missing piece in any effort to understand comparatively, not at the level of observed behavior, or at the level of the genome, but at the level of the brain circuit, how healthy individuals differ from those with illness," Mitra says. "With a circuit map we will be able to hypothesize disease-circuit phenotypes for neurodevelopmental illnesses, which, in turn, should lead to new understanding of disease causation and mechanism, and to the development of new therapeutic approaches.

"Our first challenge, however, is to engage our neuroscience colleagues and enlist them in the project to get a first draft of the healthy mouse brain. That's the necessary first step before we can begin looking at brain circuits in disease and making comparisons."

Brain Networks

The human brain contains 100 billion (10^11) neurons, which combine to form almost 1 quadrillion (10^15) electro-chemical connections. Neurons are also affected by chemical signals that come via the blood, interstitial tissues, and glial cells. If we had to understand all the activity in the brain in order to understand the brain itself, we would be lost.

Fortunately, the brain organises itself in specific ways which simplify the task of discovering how the brain works.

2007 M. Raichle PNAS

The image above reveals particular nodes which participate in important brain networks. It is important that these nodes are able to communicate with other nodes participating in specific networks. Loss of nodes -- or the communication links between them -- can have devastating effects on normal brain function.

2011 van den Heuvel and Sporns Jnl Neurosci The image above reveals the complexity of an average "connectome" which intervenes between the brain nodes participating in the 12 most important brain networks -- as measured by numbers of connections and activity levels. These networks begin to develop sometime between the 20th and 36th weeks of pregnancy. Teasing out these connections, and following their activity in real time, is quite difficult work. But it is nothing when compared to the effort involved if one tried to follow the activity of 100 billion neurons simultaneously.

It is not only the ability of the brain nodes to function that counts, it is also vital that the nodes be able to communicate with each other. Depending upon which nodes or interconnections are disrupted, different types of alteration in normal brain function will take place.