(Mis)understanding mirror neurons

This may be a bit technical for many MindBlog readers, but Hickok and Hauser offer a simple, succinct, and incisive critique of the current dogma about mirror neurons that is sufficiently important that I would like to pass it on.  They suggest, as an alternative to the common assumption that mirror neurons are involved in action understanding, that their activity instead might reflect sensory-motor learning. They illustrate this distinction with a simple graphic (in which ventral stream refers to pathways moving more through the temporal lobe of the brain - the 'what' pathway, with dorsal stream routing more through the parietal lobe - the 'where' pathway. Both pathways converge in pre-motor cortical areas such as F5):

Summary
It is hard to imagine a class of neurons that has generated more excitement than mirror neurons, cells discovered by Rizzolatti and colleagues [1] in macaque area F5 that fire both during action execution and action observation. We suggest, however, that the interpretation of mirror neurons as supporting action understanding was a wrong turn at the start, and that a more appropriate interpretation was lying in wait with respect to sensorimotor learning. We make a number of arguments, as follows. Given their previous work, it would have been natural for Rizzolatti's group to interpret mirror neurons as involved in action selection rather than action understanding. They did not make this assumption because, at the time, the data suggested that monkey behavior did not support such an interpretation. Recent evidence shows that monkeys do, in fact, exhibit behaviors that support this alternative interpretation. Thus, the original basis for claiming that mirror neurons mediate action understanding is no longer compelling. There are independent arguments against the action understanding claim and in support of a sensorimotor learning origin for mirror neurons. Therefore, the action understanding theory of mirror neuron function requires serious reconsideration, if not abandonment.
Main Text
Mirror neurons were discovered in the context of research aimed at understanding how the visual properties of objects are integrated with motor codes for action. Cells in area F5 were found to respond to visually presented objects as well as during grasping actions towards those objects. The interpretation of this circuit was that it coded a “vocabulary of motor acts and that this vocabulary can be accessed by … visual stimuli” (p. 491) [2] and that it was critical for “learning associations, including arbitrary associations between stimuli and [motor] schemas” (p. 317) [3]. This is a “‘pragmatic’ mode of processing, the function of which is to extract parameters that are relevant to action, and to generate the corresponding motor commands” (p. 320), as opposed to “‘semantic’ analysis [which is] performed in the temporal lobe” (p.314) [3]. Thus, the meaning of objects is not coded in F5, although clearly, “the semantic system can influence the pragmatic system” (p. 320) [3] (for example, we want to reach for food not snakes).

Mirror neurons were discovered within this same circuit and found to have similar sensorimotor properties [1,4]. It was even suggested that “the actions performed by other monkeys must be a very important factor in determining action selection” (p. 179) [4] and that “the [motor] vocabulary of F5 can be addressed in two ways: by objects and by events [actions]” (p. 317) [3]. Thus, the theoretical and empirical pieces were in place to interpret mirror neurons as sensorimotor association cells relevant to action selection, just like object-oriented cells (Figure 1). But this interpretation was not considered — why?

Figure 1 (click to enlarge)
Schematic models of dorsal and ventral stream function.
(A) The current dominant model [1], which holds that object- and action-oriented processes for sensorimotor integration and ‘understanding’ are organized differentially, with action understanding part of the dorsal sensorimotor stream and object ‘understanding’ part of the ventral stream. (B) A more conventional model in which object- and action-oriented processes for sensory-motor integration and understanding are organized similarly. Both models assume that semantic information from the ventral stream can modulate sensorimotor processes in the dorsal stream.

It was the mirroring property of mirror neurons that steered investigators away from a straightforward sensorimotor interpretation. The logic was, if mirror actions (for example, imitation) are not in the species' repertoire, then mirror neurons can have no motor selection function. Rizzolatti and Craighero used this argument, pitting “two main hypotheses” of mirror neuron function, imitation and action understanding; because macaques do not imitate, they argued, mirror neurons must support action understanding (p. 172) [1]. However, these authors, and the field generally, have failed to notice that other forms of mirror actions are in the macaque motor repertoire. For example, field studies show that rhesus monkeys perceive human gestures as goal-directed, including those that mimic the rhesus monkeys' species-specific signal for coalition recruitment [5]. Macaques also engage in contagious yawning, where perception of another's yawn triggers a yawn in the observer [6]. Further, experimental work has found that another's grasping actions toward one of two food receptacles serves as a cue to goal-directed grasping toward that same receptacle [7] — an experimental situation reminiscent of the mirror neuron studies. Even domesticated dogs mirror goal-directed actions of a model dog [8]; one would expect to find mirror neurons in dogs given this behavioral evidence. And lastly, rhesus monkeys comprehend actions that they are physically incapable of producing. In particular, though rhesus monkeys do not throw, they can recognize a throwing action in humans, realizing that throwing a rock is dangerous whereas throwing food is not [5].

Observed actions can serve as important inputs to action selection, including, but not necessarily limited to, mirror actions. Therefore, the motivating argument for the action understanding theory over a sensorimotor theory (for example [9]) does not hold.

Can we distinguish the sensorimotor and action understanding theories of mirror neurons? Yes: empirical findings favor the sensorimotor account by showing that action understanding and motor system function dissociate [10], that motor actions alone are insufficient to explain action understanding [5], that animals comprehend many actions that they cannot execute [10], and that sensorimotor learning can transform the mirror system [9].

In summary, a sensorimotor theory can explain the response properties of mirror neurons, does so more straightforwardly, and does not suffer the empirical roadblocks of the action understanding theory [5,10]. It is time to reconsider mirror neuron function and the neural basis of action understanding.

References
1 Rizzolatti, G., and Craighero, L. (2004). The mirror-neuron system. Annu. Rev. Neurosci. 27, 169–192.
2 Rizzolatti, G., Camarda, R., Fogassi, L., Gentilucci, M., Luppino, G., and Matelli, M. (1988). Functional organization of inferior area 6 in the macaque monkey. II. Area F5 and the control of distal movements. Exp. Brain Res. 71, 491–507.
3 Jeannerod, M., Arbib, M.A., Rizzolatti, G., and Sakata, H. (1995). Grasping objects: the cortical mechanisms of visuomotor transformation. Trends Neurosci. 18, 314–320.
4 di Pellegrino, G., Fadiga, L., Fogassi, L., Gallese, V., and Rizzolatti, G. (1992). Understanding motor events: a neurophysiological study. Exp. Brain Res. 91, 176–180.
5 Hauser, M., and Wood, J. (2010). Evolving the capacity to understand actions, intentions, and goals. Annu. Rev. Psychol 61, 303–324, C301.
6 Paukner, A., and Anderson, J.R. (2006). Video-induced yawning in stumptail macaques (Macaca arctoides). Biol. Lett. 2, 36–38.
7 Wood, J.N., Glynn, D.D., Phillips, B.C., and Hauser, M.D. (2007). The perception of rational, goal-directed action in nonhuman primates. Science 317, 1402–1405.
8 Range, F., Viranyi, Z., and Huber, L. (2007). Selective imitation in domestic dogs. Curr. Biol. 17, 868–872.
9 Heyes, C. (2010). Where do mirror neurons come from?. Neurosci. Biobehav. Rev. 34, 575–583.
10 Hickok, G. (2009). Eight problems for the mirror neuron theory of action understanding in monkeys and humans. J. Cogn. Neurosci. 21, 1229–1243.

Resilience in the face of adversity - brain correlates

Interesting work from Dolan's group on how we modulate expected aversive outcomes:

The value assigned to aversive events is susceptible to contextual influences. Here, we asked whether a change in the valuation of negative events is reflected in an altered neuronal representation of their expected aversive outcome. We show that experiencing an aversive event in the past, and choosing to experience it in the future, reduces its aversive value. This psychological change is mirrored in an altered neural representation of aversive value in the caudate nucleus and anterior cingulate cortex. Our findings indicate that subcortical regions known to track expected value such as the caudate nucleus, together with anterior cingulate cortical regions implicated in emotional modulation, mediate a revaluation in expectancies of aversive states. The results provide a striking example of a contextual sensitivity in how the brain ascribes value to events, in a manner that may foster resilience in the face of adversity.

Reciprocity engages our brain's reward system.

Interesting stuff from Phan et al:

Brain reward circuitry, including ventral striatum and orbitofrontal cortex, has been independently implicated in preferences for fair and cooperative outcomes as well as learning of reputations. Using functional MRI (fMRI) and a “trust game” task involving iterative exchanges with fictive partners who acquire different reputations for reciprocity, we measured brain responses in 36 healthy adults when positive actions (entrust investment to partners) yield positive returns (reciprocity) and how these brain responses are modulated by partner reputation for repayment. Here we show that positive reciprocity robustly engages the ventral striatum and orbitofrontal cortex. Moreover, this signal of reciprocity in the ventral striatum appears selectively in response to partners who have consistently returned the investment (e.g., a reputation for reciprocity) and is absent for partners who lack a reputation for reciprocity. These findings elucidate a fundamental brain mechanism, via reward-related neural substrates, by which human cooperative relationships are initiated and sustained.

Twitter-mood

Here is a cute study that attempts to gauge  our mood (more accurately, the 7% of American who use Twitter) throughout the day.  Play through the video that shows regional and time of day differences.  From the quickie NYTimes mention of the work: "you’re probably happiest in the morning and least satisfied about noon. Analyzing words in those posts, researchers found that Thursday is the saddest day; Sunday, the happiest. People on the West Coast who post are happier than their counterparts on the East Coast. The moods were mapped, showing happy times (greener areas) and unhappy (red areas)."

Altruism as good business - shoppers who care

Gneezy et al. add an interesting twist to studies of how we buy things. Companies loose money in attempts to enhance sales with pay-what-you-want pricing, and adding a charitable contribution to standard pricing has little effect. However, in a variation of pay-what-you-want with half going to charity, a more reasonable profit was returned. (It is not clear whether the charitable giving by the company generated additional generosity by the consumer or created additional social pressure.)

A field experiment (N = 113,047 participants) manipulated two factors in the sale of souvenir photos. First, some customers saw a traditional fixed price, whereas others could pay what they wanted (including $0). Second, approximately half of the customers saw a variation in which half of the revenue went to charity. At a standard fixed price, the charitable component only slightly increased demand, as similar studies have also found. However, when participants could pay what they wanted, the same charitable component created a treatment that was substantially more profitable. Switching from corporate social responsibility to what we term shared social responsibility works in part because customized contributions allow customers to directly express social welfare concerns through the purchasing of material goods.

Monetary favors bias judgement in unrelated domains

Work from Read Montague's group at Baylor College of Medicine in Houston, Texas, that explains how corporate sponsorship (of athletic or artistic events) can bias our judgements in a very general way:

Favors from a sender to a receiver are known to bias decisions made by the recipient, especially when the decision relates to the sender, a feature of social exchange known as reciprocity. Using an art-viewing paradigm possessing no objectively correct answer for preferring one piece of art over another, we show that sponsorship of the experiment by a company endows the logo of the company with the capacity to bias revealed preference for art displayed next to the logo. Merely offering to sponsor the experiment similarly endowed the gesturing logo of the company with the capacity to bias revealed preferences. These effects do not depend upon the size of the displayed art or the proximity of the sponsoring logo to the piece of art. We used functional magnetic resonance imaging to show that such monetary favors do not modulate a special collection of brain responses but instead modulate responses in neural networks normally activated by a wide range of preference judgments. The results raise the important possibility that monetary favors bias judgments in domains seemingly unrelated to the favor but nevertheless act in an implicit way through neural networks that underlie normal, ongoing preference judgments.

Our bias towards negative interpretation of ambiguous faces

Neta and Whalen make some interesting observations (on the usual cadre of undergraduate psychology students usually involved in such studies), showing that we have a 'better be safe than sorry' strategy in responding to ambiguous expressions of surprise that could signal either a negative or positive situation.  We pick the negative interpretation, and our background bias towards being positive or negative biases this effect.:

Low-spatial-frequency (LSF) visual information is processed in an elemental fashion before a finer analysis of high-spatial-frequency information. Further, the amygdala is particularly responsive to LSF information contained within negative (e.g., fearful) facial expressions. In a separate line of research, it has been shown that surprised facial expressions are ambiguous in that they can be interpreted as either negatively or positively valenced. More negative interpretations of surprise are associated with increased ventral amygdala activity. In this report, we show that LSF presentations of surprised expressions bias the interpretation of surprised expressions in a negative direction, a finding suggesting that negative interpretations are first and fast during the resolution of ambiguous valence.

Nuturing robots

A recent article by Benedict Carey suggests we may be heading towards a future in which instructional and emotional needs of those not able to obtain appropriate human contact are met through presentation of changing robotic emotional expressions that activate the same brain areas as normal human gestures. A report by Chaminade et al., however, on a multi-national collaboration involving the humanoid robot WE4-RII - which expresses emotions by using facial expressions and the movement of the upper-half of the body including neck, shoulders, trunk, waist, as well as arms and hands - suggests that we have some way to go:

...activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance.

The Carey article reviews a number of different robotic instructional studies that show, in spite of the attenuated effectiveness of robotic versus human emotions, that robots can engage people and teach them simple skills, including household tasks, vocabulary or, in the case of autistic children, playing, elementary imitation and taking turns.

Perceptual training enhances working memory in older adults.

Berry et al. demonstrate that training the visual discrimination of older adults enhances working memory, a cross-domain brain enhancement. (The visual discrimination task involved detecting whether a sine pattern grating was expanding or contracting. Training was adaptive such that the speed of expansion/contraction and the duration of the inter-stimulus interval scaled with improvements in response accuracy, so as to continuously challenge the trainees. The working memory test used a delayed recognition paradigm.):

Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement.

Sex promotes generation of new brain cells.

Stress usually adversely affects hippocampal structure and function in adult rats, inhibits cell division, and produces anxiety-like behavior. Leuner et al. show, however, that the stress associated with repeated (chronic) copulation has the opposite effect. The generation of new cells by cell division is stimulated and anxiety-like behaviors diminish. (Is this why I feel so mellow after...?) Here is the abstract:

Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and function have been linked to stress-induced elevations in glucocorticoids. Normalizing corticosterone levels prevents some of the deleterious consequences of stress, including increased anxiety and suppressed structural plasticity in the hippocampus. Here we examined whether a rewarding stressor, namely sexual experience, also adversely affects hippocampal structure and function in adult rats. Adult male rats were exposed to a sexually-receptive female once (acute) or once daily for 14 consecutive days (chronic) and levels of circulating glucocorticoids were measured. Separate cohorts of sexually experienced rats were injected with the thymidine analog bromodeoxyuridine in order to measure cell proliferation and neurogenesis in the hippocampus. In addition, brains were processed using Golgi impregnation to assess the effects of sexual experience on dendritic spines and dendritic complexity in the hippocampus. Finally, to evaluate whether sexual experience alters hippocampal function, rats were tested on two tests of anxiety-like behavior: novelty suppressed feeding and the elevated plus maze. We found that acute sexual experience increased circulating corticosterone levels and the number of new neurons in the hippocampus. Chronic sexual experience no longer produced an increase in corticosterone levels but continued to promote adult neurogenesis and stimulate the growth of dendritic spines and dendritic architecture. Chronic sexual experience also reduced anxiety-like behavior. These findings suggest that a rewarding experience not only buffers against the deleterious actions of early elevated glucocorticoids but actually promotes neuronal growth and reduces anxiety.

MRI evidence on how hypnosis works.

I just came across a paper by Cojan et al. on brain activity under hypnosis. While undergoing functional MRI, participants were instructed to prepare to move their hand. After a few seconds they were told whether or not to actually perform the movement. Some of the time, they were hypnotized and believed that their hand was paralyzed. Interestingly, when the volunteers were under hypnosis, the preparatory activity in motor cortex was normal; but there was increased activity in other regions related to attention, mental imagery and self-awareness. Moreover, the connectivity between these regions and motor cortex was enhanced, indicating that hypnosis doesn’t work by directly controlling motor activity, but rather through the effects of internal representations and self-monitoring processes on such activity. Here is the authors' summary of the work:

Brain mechanisms of hypnosis are poorly known. Cognitive accounts proposed that executive attentional systems may cause selective inhibition or disconnection of some mental operations. To assess motor and inhibitory brain circuits during hypnotic paralysis, we designed a go-nogo task while volunteers underwent functional magnetic resonance imaging (fMRI) in three conditions: normal state, hypnotic left-hand paralysis, and feigned paralysis. Preparatory activation arose in right motor cortex despite left hypnotic paralysis, indicating preserved motor intentions, but with concomitant increases in precuneus regions that normally mediate imagery and self-awareness. Precuneus also showed enhanced functional connectivity with right motor cortex. Right frontal areas subserving inhibition were activated by nogo trials in normal state and by feigned paralysis, but irrespective of motor blockade or execution during hypnosis. These results suggest that hypnosis may enhance self-monitoring processes to allow internal representations generated by the suggestion to guide behavior but does not act through direct motor inhibition.

Directly controlling 'fear' cells in the brain.

LeDoux and collaborators have done the clever experiment (in rats) of introducing an optically activated molecular label into cells in the amygdala thought to be causal in fear conditioning. Activation of these cells by light just after presentation of a auditory sensory cue (but with no aversive stimulus) caused the rats to exhibit behavioral fear responses when the cue was subsequently presented.

Humans and animals can learn that specific sensory cues in the environment predict aversive events through a form of associative learning termed fear conditioning. This learning occurs when the sensory cues are paired with an aversive event occuring in close temporal proximity. Activation of lateral amygdala (LA) pyramidal neurons by aversive stimuli is thought to drive the formation of these associative fear memories; yet, there have been no direct tests of this hypothesis. Here we demonstrate that viral-targeted, tissue-specific expression of the light-activated channelrhodopsin (ChR2) in LA pyramidal cells permitted optical control of LA neuronal activity. Using this approach we then paired an auditory sensory cue with optical stimulation of LA pyramidal neurons instead of an aversive stimulus. Subsequently presentation of the tone alone produced behavioral fear responses. These results demonstrate in vivo optogenetic control of LA neurons and provide compelling support for the idea that fear learning is instructed by aversive stimulus-induced activation of LA pyramidal cells.

Fool the brain to enhance performance with a carbohydrate rinse

Kolata reports on exercise physiologists stumbling on an unexpected feature: simply rinsing the mouth with a carbohydrate solution stimulates receptors that report to the brain, causing it to instruct increased intensity and duration of effort in anticipation of an imminent food reward.

Our dread of idleness

Being a hyper-purposeful person myself, I've always been attracted to the opposite pole represented by The Idler,  both the original book and the subsequent magazine whose intention is "to return dignity to the art of loafing, to make idling into something to aspire towards rather than reject."  Thus I thought this piece by Hsee et al. worth passing on. They set up experiments in which people who voluntarily choose busyness report being happier than those who voluntarily choose idleness. Further, people who are forced into busyness report being happier than those who are forced into idleness. People choose to be idle if they do not have reason to be busy, but that even a specious justification can prompt them to seek busyness.  Here is their abstract:

There are many apparent reasons why people engage in activity, such as to earn money, to become famous, or to advance science. In this report, however, we suggest a potentially deeper reason: People dread idleness, yet they need a reason to be busy. Accordingly, we show in two experiments that without a justification, people choose to be idle; that even a specious justification can motivate people to be busy; and that people who are busy are happier than people who are idle. Curiously, this last effect is true even if people are forced to be busy. Our research suggests that many purported goals that people pursue may be merely justifications to keep themselves busy.

Their (slightly edited) speculations are interesting to read:

We speculate that the concurrent desires for busyness and for justification are rooted in evolution. In their strife for survival, human ancestors had to conserve energy to compete for scarce resources; expending energy without purpose could have jeopardized survival. With modern means of production, however, most people today no longer expend much energy on basic survival needs, so they have excessive energy, which they like to release through action. Yet the long-formed tendency to conserve energy lingers, making people wary of expending effort without purpose.

Our research also complements recent research of Airely et al.  that suggests that people work in order to search for meaning (i.e., achievement and recognition), our study suggests that people search for meaning in order to work. In Greek mythology, Sisyphus’ punishment, imposed by Zeus, was to eternally roll a rock toward the top of a hill, never to arrive there. The research of Ariely et al. predicts that Sisyphus would have been happier if Zeus had allowed the rock to reach the top of the hill and had then recognized Sisyphus’ achievement. Our research suggests that Sisyphus was better off with his punishment than he would have been with a punishment of an eternity of doing nothing, and that he might have chosen rolling a rock over idleness if he had been given a slight reason for doing it.

Idleness is potentially malignant. If idle people remain idle, they are miserable. If idle people become busy, they will be happier, but the outcome may or may not be desirable, depending on the value of the chosen activity. Busyness can be either constructive or destructive. Ideally, idle people should devote their energy to constructive courses, but it is often difficult to predict which actions are constructive (e.g., are business investments or scientific discoveries always constructive?), and not every idle individual is capable of constructive contributions. Idle people often engage in destructive busyness (from inner-city crimes to cross-border wars); as Hippocrates observed in Decorum, “Idleness and lack of occupation tend―nay are dragged―towards evil.”

We advocate a third kind of busyness: futile busyness, namely, busyness serving no purpose other than to prevent idleness. Such activity is more realistic than constructive busyness and less evil than destructive busyness. However, as we demonstrated in the no-justification (same-candy or same-design) condition of our research, most people will not voluntarily choose futile busyness.

This is where paternalism can play a role. For example, homeowners may increase the happiness of their idle housekeepers by letting in some mice and prompting the housekeepers to clean up. Governments may increase the happiness of idle citizens by having them build bridges that are actually useless. Indeed, some such interventions already exist: Airports have tried to increase the happiness (or reduce the unhappiness) of passengers waiting at the baggage carousel by increasing the distance between the gate and the baggage claim area, forcing them to walk far rather than wait idly. Similar intentions may be applied at the societal level. Although these strategies may not be ethical, we believe that futile busyness trumps both idleness and destructive busyness.

Mindblog on the road

I'm in Ft. Lauderdale today through next Tuesday, attending the 85th birthday party/piano concert David Goldberger, the fellow I did a four-hands concert with last March. This may have an effect on the frequency of next week's posts.

Acetaminophen (tylenol) reduces physical and social pain.

DeWall et al. show that an anti-pain medication that acts on the brain's pain pathways, reduces both physical and social pain:

Pain, whether caused by physical injury or social rejection, is an inevitable part of life. These two types of pain—physical and social—may rely on some of the same behavioral and neural mechanisms that register pain-related affect. To the extent that these pain processes overlap, acetaminophen, a physical pain suppressant that acts through central (rather than peripheral) neural mechanisms, may also reduce behavioral and neural responses to social rejection. In two experiments, participants took acetaminophen or placebo daily for 3 weeks. Doses of acetaminophen reduced reports of social pain on a daily basis. We used functional magnetic resonance imaging to measure participants’ brain activity, and found that acetaminophen reduced neural responses to social rejection in brain regions previously associated with distress caused by social pain and the affective component of physical pain (dorsal anterior cingulate cortex, anterior insula). Thus, acetaminophen reduces behavioral and neural responses associated with the pain of social rejection, demonstrating substantial overlap between social and physical pain.

A growing isolated brain can organize itself.

How much of the development of our brain's cortex depends on it being able to talk with other parts of the brain and body? Apparently, not as much as had been thought. Zhou et al. have used a mouse mutant in which the neocortex had been disconnected from the rest of the brain in order to analyze the development of the surface map (which might be compared to a geopolitical map supported by an infrastructure of shipping, communication, and regulatory networks). In normal mice, a few weeks of postnatal development complete the brain's organization; the mutant mice survive during this phase but die at about 3 weeks of age. During these weeks, the mutant mice, despite having disconnected brains, display a variety of behaviors: eating, drinking, walking, and swimming. Thus, "protomap" formation, namely cortical lamination and formation of areas, proceed normally in absence of extrinsic connections, but survival of projection neurons and acquisition of mature morphological and some electrophysiological features depend on the establishment of normal cortical–subcortical relationships.

Dopamine, Time, and Our Impulsivity

Yet another fascinating piece of work from the group around Ray Dolan at the London Wellcome Trust Center for Neuroimaging. They show that enhancing dopamine activity can increase our propensity to choose smaller–sooner over larger–later rewards:

Disordered dopamine neurotransmission is implicated in mediating impulsiveness across a range of behaviors and disorders including addiction, compulsive gambling, attention-deficit/hyperactivity disorder, and dopamine dysregulation syndrome. Whereas existing theories of dopamine function highlight mechanisms based on aberrant reward learning or behavioral disinhibition, they do not offer an adequate account of the pathological hypersensitivity to temporal delay that forms a crucial behavioral phenotype seen in these disorders. Here we provide evidence that a role for dopamine in controlling the relationship between the timing of future rewards and their subjective value can bridge this explanatory gap. Using an intertemporal choice task, we demonstrate that pharmacologically enhancing dopamine activity increases impulsivity by enhancing the diminutive influence of increasing delay on reward value (temporal discounting) and its corresponding neural representation in the striatum. This leads to a state of excessive discounting of temporally distant, relative to sooner, rewards. Thus our findings reveal a novel mechanism by which dopamine influences human decision-making that can account for behavioral aberrations associated with a hyperfunctioning dopamine system.

Motivating only half our bodies.

Schmidt et al. do a simple experiment to show that motivation need not be a person-level concept, our left and right hemispheres can be separately motivated:

Motivation is generally understood to denote the strength of a person’s desire to attain a goal. Here we challenge this view of motivation as a person-level concept, in a study that targeted subliminal incentives to only one half of the human brain. Participants in the study squeezed a handgrip to win the greatest fraction possible of each subliminal incentive, which materialized as a coin image flashed in one visual hemifield. Motivation effects (i.e., more force exerted when the incentive was higher) were observed only for the hand controlled by the stimulated brain hemisphere. These results show that in the absence of conscious control, one brain hemisphere, and hence one side of the body, can be motivated independently of the other.

The mind is the body - tumor suppression by enriched environment

An amazing article by Cao et al. brings home the intimate attachment between mental well-being and health - in mice (and by implication, for us too).   An enriched environment promotes formation of a nerve growth factor which in turn inhibits tumor growth through a series of biochemical steps, shown in the summary graphic before the abstract. A commentary by Jonah Lehrer notes that we need "a new metaphor for the interactions of the brain and body. They aren't simply connected via some pipes and tubes. They are emulsified together, so hopelessly intertwined that everything that happens in one affects the other. Holism is the rule."

Cancer is influenced by its microenvironment, yet broader, environmental effects also play a role but remain poorly defined. We report here that mice living in an enriched housing environment show reduced tumor growth and increased remission. We found this effect in melanoma and colon cancer models, and that it was not caused by physical activity alone. Serum from animals held in an enriched environment (EE) inhibited cancer proliferation in vitro and was markedly lower in leptin. Hypothalamic brain-derived neurotrophic factor (BDNF) was selectively upregulated by EE, and its genetic overexpression reduced tumor burden, whereas BDNF knockdown blocked the effect of EE. Mechanistically, we show that hypothalamic BDNF downregulated leptin production in adipocytes via sympathoneural β-adrenergic signaling. These results suggest that genetic or environmental activation of this BDNF/leptin axis may have therapeutic significance for cancer.