Spindle Neurons: The Next New Thing?

In a neuroanatomical tour de force, Nimchinsky and colleagues (1999) obtained access to samples of the anterior cingulate cortex (and other cortical regions) from 28 different primate species, from prosimians to anthropoids to great apes to humans. They processed the samples with a Nissl stain to identify neuronal cell bodies in the cerebral cortex, a structure that (generally) consists of six layers. Spindle neurons are a unique type of neuron found in layer Vb in the ACC and frontoinsular cortex of humans. This is nothing new; spindle neurons (also called Von Economo neurons) were first identified in the 19th century by W. Betz (of the eponymous Betz cell fame, I presume) and by Nobel laureate Santiago Ramón y Cajal. What was new in 1999 was the finding that only humans and great apes have spindle neurons.

Nimchinsky EA, Gilissen E, Allman JM, Perl DP, Erwin JM, Hof PR. (1999). A neuronal morphologic type unique to humans and great apes. Proc Natl Acad Sci 96:5268-73.

We report the existence and distribution of an unusual type of projection neuron, a large, spindle-shaped cell, in layer Vb of the anterior cingulate cortex of pongids and hominids. These spindle cells were not observed in any other primate species or any other mammalian taxa, and their volume was correlated with brain volume residuals, a measure of encephalization in higher primates. These observations are of particular interest when considering primate neocortical evolution, as they reveal possible adaptive changes and functional modifications over the last 15-20 million years in the anterior cingulate cortex, a region that plays a major role in the regulation of many aspects of autonomic function and of certain cognitive processes. That in humans these unique neurons have been shown previously to be severely affected in the degenerative process of Alzheimer's disease suggests that some of the differential neuronal susceptibility that occurs in the human brain in the course of age-related dementing illnesses may have appeared only recently during primate evolution.

Here's what John Allman's Lab at Cal Tech says about their work:

Our lab has investigated the anatomical structure of the Von Economo (spindle) neurons in anterior cingulate and fronto-insular cortex. Based on functional imaging studies of these brain areas and our studies of the expression of neurotransmitter receptors on these cells, we think they participate in fast, intuitive social decision-making. We have found that the Von Economo neurons emerge mainly in the first three years after birth. We also have evidence that in autistic subjects the Von Economo neurons are abnormally located, possibly as a result of a migration defect. This abnormality may be at least partially responsible for defective social intuition in autism.

Somehow, the "spindle neuron" meme hasn't caught on like the "mirror neuron" meme. Is it because spindle neurons have been only been described anatomically (not physiologically), while the reverse is true for mirror neurons? Anatomically speaking, do we know much about mirror neurons? Here's what Rizzolatti and Craighero (2004) have to say about them:

Mirror neurons are a particular class of visuomotor neurons, originally discovered in area F5 of the monkey premotor cortex, that discharge both when the monkey does a particular action and when it observes another individual (monkey or human) doing a similar action (Di Pellegrino et al. 1992, Gallese et al. 1996, Rizzolatti et al. 1996a).

from Rizzolatti G, Craighero L. (2004). The mirror-neuron system. Annu Rev Neurosci. 27:169-92.

In the elegantly titled article, The importance of being agranular, Stewart Shipp reviews evidence that approximately 10% of recorded cells in premotor area F5 in the macaque monkey can be classified as mirror neurons. He also points out an interesting conundrum regarding the anatomical organization of motor cortex: it's agranular, meaning it's lacking the granule cell layer (layer IV), the typical termination point for feedforward sensory information. Area 7b (or PF) in the rostral inferior parietal lobule provides the main parietal input to F5. Without going into too many details, it seems the anatomical circuitry of visual input to F5 is pretty complicated. Anyone who studies mirror neurons (or who does fMRI studies of "empathy and the mirror neuron system") should read these two papers:

Geyer S, Matelli M, Luppino G, Zilles K. (2000). Functional neuroanatomy of the primate isocortical motor system. Anat Embryol 202:443-74

Shipp S. (2005). The importance of being agranular: a comparative account of visual and motor cortex. Philos Trans R Soc Lond B Biol Sci. 360:797-814.

Everybody in Mirror Neurons!

Gap ad, with mirror neurons by Rizzolatti & Craighero (2004)

Everybody's talking about mirror neurons!!


Con: Mixing Memory and Neurotopia (version 2.0)

Mirror Neurons, Language, and Meaning (Oh, My!)

Everybody Post About Mirror Neurons!!!


Less Con: The Frontal Cortex

Are Mirror Neurons Too Cool?


Pro: Small Gray Matters

Mirror neurons aren’t really all that bad…


ADDENDUM: and there's more!

Neurofuture: Mirror meme

Mind Hacks: Reflected glory

And the post that really started it all,

BrainTechSci: Much Ado About Mirror Neurons

Mirror Neurons Join Marilyn Monroe Neurons and Halle Berry Neurons in the Human Hippocampus

Move over, Marilyn Monroe neurons and Halle Berry neurons... The cellular media darlings of action observation and action execution would like to join you in the human hippocampus and surrounding medial temporal lobe (MTL) areas critical for memory.

"What?" you say. "Direct evidence for the existence of mirror neurons has been obtained from single cell recordings in monkeys in specific brain regions. These include the ventral premotor cortex (area F5) and the inferior parietal lobule (Rizzolatti & Sinigaglia, 2010), not the hippocampus!"


Figure 1 (Rizzolatti & Sinigaglia, 2010): The parieto-frontal mirror network. Lateral view of the macaque brain. The coloured areas represent the areas of the parieto-frontal circuit containing mirror neurons: the ventral premotor cortex (area F5), area PFG (located between parietal areas PF and PG) and the anterior intraparietal area (AIP)... The parieto-frontal circuit receives high-order visual information from areas located inside the superior temporal sulcus (STS) and the inferior temporal lobe (IT). Neither of these temporal regions has motor properties. The parieto-frontal circuit is under control of the frontal lobe (area F6 or pre-supplementary motor area and the ventral prefrontal cortex (VPF)). The inset provides an enlarged view of area F5. IAS, inferior limb of the arcuate sulcus; LIP, lateral intraparietal area; VIP, ventral intraparietal area.

Yet we've been led to believe that a new study published in Current Biology (Mukamel et al., 2010) has recorded from mirror neurons in the human brain for the first time. Last Friday, BPS Research Digest asked:

Is this the first ever direct evidence for human mirror neurons?

...Although recordings from single cells in the brains of monkeys have identified 'mirror' neurons that respond both to the execution of a movement and the observation of another agent performing that same movement, the existence of such cells in humans has, up until now, been inferred only from indirect evidence, particularly brain imaging. Now Roy Mukamel and colleagues have provided what appears to be the first ever direct evidence, using implanted electrode recordings of single cells, for the existence of mirror neurons in humans.

The short answer to this question is "no" (unless you want to dilute the meaning of "mirror neurons" beyond recognition). To briefly summarize, the participants in the study were 21 patients with pharmacologically intractable epilepsy. Depth electrodes were implanted into their brains to monitor for seizures, in advance of a possible surgical intervention to remove the epileptic focus. The electrode locations were constrained by clinical considerations and included regions in the medial frontal cortex (supplementary motor area, anterior cingulate cortex) and the medial temporal lobe (amygdala, hippocampus, parahippocampal gyrus, entorhinal cortex). The ventral premotor cortex and inferior parietal lobe were not targeted.

The experimental protocol consisted of 3 tasks: Grasp, Facial expressions and Control.

During Grasp, subjects were presented with video clips of a hand grasping a mug and with the words ‘Finger’ or ‘Hand’. They were instructed to grasp a mug with precision grip or whole hand prehension when the words ‘Finger’ or ‘Hand’, respectively, were presented and to simply observe when the video clips were played. During Facial expressions, subjects were presented with a picture of a smiling or a frowning face and with the word ‘Smile’ or ‘Frown’. They were instructed to perform the corresponding action when the words were presented and to simply observe when the pictures were presented... In the Control task, subjects were presented with the words used as cues in the Grasp and Facial expression parts of the experiment and were instructed to covertly read the words and refrain from making hand movements or facial gestures.

Results are depicted in Table 1 below (click on image for a larger view).

In each brain region, only a minority of cells responded with an increased (or decreased) firing rate during both observation and execution of the same action. Percentages of these Observation/Execution neurons ranged from a low of 2% in dorsal anterior cingulate cortex to 11% in hippocampus, 12% in parahippocampal gyrus, and 14% in supplementary motor area. The MTL regions also contain neurons that respond during the spontaneous recall of episodic memories (Gelbard-Sagiv et al., 2008). So how can you tell if a neuronal response in the current experiment is related to memory recall or to action observation/execution? You can't, but that doesn't matter!

The action observation/execution matching neurons in the medial temporal lobe may match the sight of actions of others with the memory of those same actions performed by the observer. Thus during action-execution, a memory of the executed action is formed, and during action-observation this memory trace is reactivated. This interpretation is in line with the hypothesis of multiple mirroring mechanisms in the primate brain, a hypothesis that can easily account for the presence of mirroring cells in many cortical areas.

"Now wait a minute," said Professor Patricia Churchland [as paraphrased by Prof. Greg Hickok in Talking Brains]. "If mirror neurons are all over the brain then don't they lose their explanatory power?"

Good point.

Another issue is whether a given single- or multi-unit recording responded by increasing or decreasing its firing rate relative to the passive condition. It could be either, or both:

Among the 68 action observation/execution matching cells [out of 1177 total cells recorded], 33 increased their firing rate during both observation and execution of a particular action. In contrast, 21 other neurons decreased their firing rate during both conditions. These types of responses have been previously reported in monkeys and birds. Furthermore, 14 neurons increased their firing rate during one condition and decreased it during the other.

Really? Neurons can show inhibitory responses to observation and execution, or mismatched responses, and still be considered "mirror neurons"?

Also notable is that the paper did not refer to previous results from the same lab on Marilyn Monroe neurons (Quian Quiroga et al., 2009) and Halle Berry neurons (Quian Quiroga et al., 2005).¹ The new "mirroring cells" are apparently intermixed with individual neurons that show hyperspecific responses to pictures of celebrities (taken from various angles, in and out of character) and even to their printed names and voices. In each brain region, about 10% of the cells were responsive to stimulation of any sort. Of these minority neurons, 0% in parahippocampal cortex, 14% in amygdala, 35% in entorhinal cortex, and 38% in hippocampus showed "triple invariance" to presentation as pictures, sound, and text (Quian Quiroga et al., 2009).

The hyperspecific neuronal responses included a Jennifer Aniston+Brad Pitt cell (not Aniston alone), a Pamela Anderson cell that responded to a caricature of her and to her printed name, and a Kobe Bryant cell. A specific double dissociation was reported between a Halle Berry neuron and a Mother Teresa neuron (i.e, one cell showed a response to Halle Berry but not Mother Teresa, and the other cell showed a response to Mother Teresa but not Halle Berry).

Below is one of my favorites, the rare Robert Plant neuron that responds to images, sounds, and text depicting the former Led Zeppelin singer. I wonder what would happen if he had a closed shirt and shorn hair in some of the pictures?


Figure S17 (Quian Quiroga et al., 2009). A single unit in the entorhinal cortex selectively activated by pictures, sound and text presentations of Robert Plant, singer of the band ‘Led Zeppelin’, which was known to the patient.

But what about hybrid Halle Berry mirror neurons? How does one integrate the results from all these studies? Who's to say that you couldn't find a Jennifer Aniston action observation/action imitation neuron if you looked hard enough? Would it still be considered a "mirroring neuron" if Lisa Kudrow did not elicit the same response? What if all the cast members of Friends could evoke the observation/imitation response, but not the cast members of Seinfeld?

In conclusion, Mukamel et al., (2010) have this to say about their "mirror neuron" results:

The functional significance of the mirror mechanism most likely varies according to the location of mirror neurons in different brain areas. For example, the mirror mechanism in the insula might underlie the capacity to understand a specific emotion (disgust) in others, whereas the mirror mechanism in the parietofrontal circuit may help understanding the goal of observed motor acts and the intentions behind them. Here we show cellular mirroring mechanisms in areas relevant to movement initiation and sequencing (SMA) and to memory (medial temporal lobe). Whereas these hypotheses have yet to be tested more carefully, these results demonstrate the presence of mirror mechanisms in humans at the single neuron level and in areas functionally different from the ones previously described in the literature.

So are mirror neurons everywhere? Have they lost their explanatory power?


Footnote

¹ One of the Fried lab papers was cited in passing but only to say how the new "mirror neuron" results were not due to representational invariance of grasping or smiling, because cell firing rates did not change in the passive control condition. However, the lack of a significant response in the control condition was required before including a cell(s) in the action execution bin. I can imagine that quite a few neurons responded in a condition where subjects were told, "covertly read the words and refrain from making hand movements or facial gestures" -- especially in the SMA and pre-SMA, which are involved not only in motor planning but in motor inhibition as well.

References

Gelbard-Sagiv H, Mukamel R, Harel M, Malach R, Fried I. (2008). Internally generated reactivation of single neurons in human hippocampus during free recall. Science 322:96-101.

Mukamel, R., Ekstrom, A., Kaplan, J., Iacoboni, M., & Fried, I. (2010). Single-Neuron Responses in Humans during Execution and Observation of Actions. Current Biology DOI: 10.1016/j.cub.2010.02.045

Quian Quiroga, R., Kraskov, A., Koch, C., & Fried, I. (2009). Explicit Encoding of Multimodal Percepts by Single Neurons in the Human Brain. Current Biology, 19 (15), 1308-1313 DOI: 10.1016/j.cub.2009.06.060

Quiroga, R., Reddy, L., Kreiman, G., Koch, C., & Fried, I. (2005). Invariant visual representation by single neurons in the human brain. Nature, 435 (7045), 1102-1107 DOI: 10.1038/nature03687

Rizzolatti G, Sinigaglia C. (2010). The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations. Nat Rev Neurosci. 11:264-74.

Music and Empathy

I've been reading the book Rat Girl, a memoir by musician Kristin Hersh, who started the band Throwing Muses in 1980, at the age of 14 (along with Tanya Donelly, Leslie Langston, and David Narcizo). The book recounts an eventful year in her life (1985-86) when, among other things, she is diagnosed with bipolar disorder and her band is signed to record label 4AD.

Below she describes the intense empathic connection between the band and their music and their audience, which struck me as a profound (and idealistic) way to live:

Our band was started on these two bullshit principles -- well, they're more like bullshit wishes, but here they are:

    1. That people should be able to touch one another and feel each other's pain. Physically, like you should be able to touch someone's cheek and feel their toothache; and emotionally, if you move someone, touch them deeply, you have to take responsibility for that depth of feeling and care about them.
    So it isn't just pain we should feel in each other -- happiness should seep out of pores, and clouds of jealousy and all the different kinds of love and disappointment should float around us. We could walk in and out of people's clouds and know what they're feeling. That'd be the kindest way to live on planet earth.

    2. That maybe our essential selves are drunk -- not wasted, just kinda buzzed enough to let go. If we were always a little tipsy, we'd be light, nonjudgmental, truthful. Our hang-up'd be shaken off, there'd be no second-skin barriers to honesty. Oh, and also no hangovers.

    We figure if those two things are true, then it'd be OK for a band to sound like we do: sorta painful and a little out of control. We'd play what the audience felt and feel it at the same time and they'd feel it reflected back to them in sound and we'd all care about each other's stories and clouds of feeling and ... good luck with that I think miserably through my stage fright, trudging past the knitters, hippies, junkies, drunks, painters and psychos.

-from Rat Girl, p. 42-43.

It's hard to maintain that level of emotional empathy without collapsing from the weight of pain and joy and exhaustion. One would need superpowers to hold up under such unguarded transparency and depth of feeling.

I'm wiped
I'm so tired

Carry me for a little while

Carry me for a little while

Carry me for a little while

Carry me for a little while

-Kristin Hersh, "Your Dirty Answer"

from: Superpower Wiki

Music and Mirror Neurons

The mirror neurons, it would seem, dissolve the barrier between self and others. I call them "empathy neurons" or "Dalai Llama neurons".

-- MIRROR NEURONS AND THE BRAIN IN THE VAT
by V.S. Ramachandran

Even the most ardent reductionists might be at a loss when contemplating how to reduce profound human experiences to a map of hemodynamic or electrical changes in the brain. But don't despair! Of course we should all know by now that music's ability to transmit emotion and elicit empathy is mediated by mirror neurons (Molnar-Szakacs & Overy, 2006):

It has recently been proposed that music is best understood as a form of communication in which acoustic patterns and their auditory representations elicit a variety of conscious experiences (Bharucha et al., 2006). Here we review some recent evidence on the neural basis of musical processing in relation to two other modes of communication, language and action, both of which have been described as supported by the human mirror neuron system. We hypothesize that the powerful affective responses that can be provoked by apparently abstract musical sounds are supported by this human mirror neuron system, which may subserve similar computations during the processing of music, action and linguistic information.

So the magical mirror neuron system is responsible for understanding very diverse types of stimuli (music, action, and language) and for evoking concomitant emotional responses to them. Such accounts always extrapolate from single unit recordings of mirror neurons in ventral premotor area F5 and inferior parietal lobule of monkeys to fMRI results in humans. In monkeys, a mirror neuron increases its firing rate when the animal performs an action, and when the animal watches someone else perform the action (Rizzolatti & Sinigaglia, 2010). As far as I know, no one has recorded mirror neuron activity directly from inferior prefrontal or parietal regions in humans.¹

This is not to say that mirror neurons do not exist in humans, just that the scope of the human "mirror neuron system" has expanded beyond recognition into an unfalsifiable theory: ²

"Now wait a minute," said Professor Patricia Churchland [as paraphrased by Prof. Greg Hickok in Talking Brains]. "If mirror neurons are all over the brain then don't they lose their explanatory power? Aren't we now just back to our old friend, the How Does the Brain Work Problem?"

A recent post at Brain Myths even suggests that mirror neurons might be The Most Hyped Concept in Neuroscience. Despite the hyperbole from Ramachandran, the reality is more mundane. For instance, we can understand actions we cannot perform:

The ubiquitous idea that mirror neurons “cause” us to feel other people’s emotions can be traced back to the original context in which they were discovered – the motor cells in the monkey brain that responded to the sight of another person performing an action. This led to the suggestion that mirror neurons play a causal role in allowing us to understand the goals behind other people’s actions. By representing other people’s actions in the movement-pathways of our own brain, so the reasoning goes, these cells provide us with an instant simulation of their intentions – a highly effective foundation for empathy.

...The biggest and most obvious problem for anyone advocating the idea that mirror neurons play a central role in our ability to understand other people’s actions, is that we are quite clearly capable of understanding actions that we are unable to perform.³

In the case of music, Molnar-Szakacs and Overy (2006) suggest its traditional relationship to motion (drumming, singing, etc.) engages the mirror neuron system.  Indeed, a recent study has claimed that music and movement share a dynamic structure that supports universal expressions of emotion. Nonetheless, we can appreciate an energetic drum solo without being able to play the drums.

But this general line of reasoning raises the following questions: (1) Are musicians more empathetic? and (2) Do they engage the mirror neuron system to a greater extent than those without musical training?

We'll examine these questions in a subsequent post...


Footnotes

¹ "Mirror neuron-like" activity has been recorded from the human hippocampus (Mukamel et al., 2010), but that's another story...  Archives of mirror neuron criticism can be found at Talking Brains and The Neurocritic.

² Or in the words of Dr. Greg Hickok:

I think the mirror neuron folks have a serious problem on their hands: there is apparently no empirical result that can falsify the theory. If a mirror neuron shows up in an unexpected place, it is a new part of the mirror system. If a mirror neuron's activity dissociates from action understanding, it was not coding understanding at that moment. If damage to the motor system doesn't disrupt understanding, it is because that part of the motor system isn't mirroring.

³ Some have even claimed that mirror neurons can account for "certain listeners' misattribution of anger in the music of avant garde jazz saxophonists" (Gridley & Hoff, 2006). Is this because these listeners cannot play avant garde jazz saxophone?


References

Molnar-Szakacs, I., & Overy, K. (2006). Music and mirror neurons: from motion to 'e'motion. Social Cognitive and Affective Neuroscience, 1 (3), 235-241. DOI: 10.1093/scan/nsl029

Rizzolatti G, Sinigaglia C. (2010). The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations. Nat Rev Neurosci. 11:264-74.

I don't judge people
I just watch them 'til it's time to look away
I want to look away now
Somebody's coming
I don't want to live backwards
I don't want even to look backwards
It's not my fault...

-Kristin Hersh, "Your Dirty Answer"

Mirror Neurons Control Hard-ons?

from MR BEAN IN TOILET

Everyone knows that mirror neurons control the universe. Now, a study by Mourus and colleagues supposedly tells us that mirror neurons control the most important thing in the universe!

Mirror neurons control erection response to porn

14:15 16 June 2008
NewScientist.com news service
Alison Motluk

. . .

Harold Mouras, at University of Picardie Jules Verne in Amiens, France, and his colleagues wanted to understand the cerebral underpinnings of visually-induced erections.

They suspected there might be a role for mirror neurons, a special class of brain cell that fires both when people perform an action and when they observe it being performed.

The researchers invited eight young men into the lab and asked them to view three types of video clips. Along with late-night fishing documentaries and snippets of Mr Bean, the volunteers got to see erotic videos of [XXX]...¹

This isn't the first study to invoke the specter of mirror neurons as a critical aspect of responsiveness to viewing porn. Ponsetti et al. (2006) showed pictures of male and female sexually aroused genitals to gay and straight male and female participants [see An "Endophenotype" For Sexual Orientation? for a full description of that study]. The authors summarized their results as follows:

Consistent with our prediction, the ventral striatum and the centromedian thalamus, showed a stronger neuronal response to preferred relative to non-preferred stimuli. Likewise, the ventral premotor cortex which is a key structure for imitative (mirror neurons) and tool-related (canonical neurons) actions showed a bilateral sexual preference-specific activation, suggesting that viewing sexually aroused genitals of the preferred sex triggers action representations of sexual behavior.

At the time, I said:

Here's a thought. According to Wikipedia,

a mirror neuron is a neuron which fires both when an animal performs an action and when the animal observes the same action performed by another (especially conspecific) animal. Thus, the neuron "mirrors" the behavior of another animal, as though the observer were himself performing the action.

The Neurocritic is as skeptical as anyone about the mirror neuron craze, but if the PMv activity in this experiment is really imitative in nature, or even "empathetic" (instead of motor imagery or motor preparation), then wouldn't same-sex genitals elicit greater activity than opposite-sex genitals, regardless of sexual orientation?

Anyway. Now on to the present study. Here, Mourus et al. went further by using penile plethysmography:

To investigate the hypothesis that the activation of the mirror-neuron system could be part of the neural mechanisms regulating visually-induced sexual arousal, including the erectile response, we examined whether the response of the mirror-neuron system to sexually stimulating video clips is correlated with the erectile response of healthy volunteers.

The participants were ten healthy heterosexual males somewhere between the ages of 18 and 60. The authors hypothesized that

a neural pathway linking the mirror-neuron system to neural structures controlling erection could be represented by the efference of the frontal operculum – a region containing mirror neurons - to the insula.²

The ventral premotor cortex in Brodmann area 6 is posterior to the frontal operculum (Tomassini et al., 2007). Do we really know that the frontal operculum contains mirror neurons? The most [only] definitive evidence for mirror neuron-type activity is from single-unit recording, not from fMRI. Do monkeys even have a frontal operculum? Yes, but it seems to be mostly gustatory.

Mirror Neuron Erection Study a "BOLD" One

...at least, according to Ramachandran:

Vilayanur Ramachandran, at the University of California at San Diego, who also studies mirror neurons, calls it a "bold" study, and congratulates the group on defying the taboo on studying human sexual physiology.

While he thinks it is perfectly plausible that mirror neurons play a role in how porn turns us on, he says more needs to be done to understand what that role is. For a start, he says, a large number of the brain's structures seem to be involved, not just the pars opercularis, and the interaction between these regions in response to porn is unclear.

"It doesn't give you an experimental lever into the problem," he adds.

And while Ramachandran agrees that the timing of mirror neuron activation and erection is probably critical, fMRI isn't accurate enough to show clearly what is going on with these brain regions over such short time frames.

Ramachandran isn't usually one to show restraint in interpreting data, but here he's right that the BOLD signal was correlated positively with the plethysmographic signal in multitude of brain regions. The authors focus on Frontal operculum, Precentral gyrus, Middle frontal gyrus, Postcentral gyrus, Inferior parietal lobule, Postcentral sulcus, Supramarginal gyrus, Anterior insula, and Posterior insula in the main body of the text, but one can...

(see exhaustive list of regions in Tables 1 and 2 of the online electronic supplementary material)

...once they're online (they're not yet).

ADDENDUM: My criticism of this statement, "Pars opercularis (Brodmann area [BA] 44) is a likely homologue of a subdivision of area F5 of monkeys" appears to be justified. In a recent review of 24 fMRI studies, Morin and Grèzes (2008) discovered that

Observing biological actions with a physical target, compared to a visual control showing no action at all, consistently activated the ventral premotor cortex (BA 6), and did so significantly more than observing target-less actions (with the same control). In contrast, the activity in BA 44 ("Broca’s area") was not modulated by the presence or absence of targets. We propose that the ventral precentral gyrus, and not BA 44, shares the visual properties of "mirror" neurons found in area F5 of the macaque brain.

Footnotes

¹ Edited to avoid search engine hits to this blog from terms like "s*roking n**ed women, enjoying f***atio and engaging in interco**se."

² The insula -- it's not just for the concept of fairness any more!

References

MOURAS H, STOLERU S, MOULIER V, PELEGRINI-ISSAC M, ROUXEL R, GRANDJEAN B, GLUTRON D, BITTOUN J. (2008). Activation of mirror-neuron system by erotic video clips predicts degree of induced erection: an fMRI study. NeuroImage DOI: 10.1016/j.neuroimage.2008.05.051.

Although visually-induced erection is a common occurrence in human male behaviour, the cerebral underpinnings of this response are not well-known. We hypothesized that the magnitude of induced erection would be linearly correlated with the activation of the mirror-neuron system in response to sexually explicit films. When presented with sexual video clips, eight out of ten healthy subjects had an erectile response demonstrated through volumetric penile plethysmography. The level of activation of the left frontal operculum and of the inferior parietal lobules, areas which contain mirror neurons, predicted the magnitude of the erectile response. These results suggest that the response of the mirror-neuron system may not only code for the motor correlates of observed actions, but also for autonomic correlates of these actions.

Morin O, Grèzes J. (2008). What is "mirror" in the premotor cortex? A review. Neurophysiol Clin. 38:189-195.

Ponseti J, Bosinski HA, Wolff S, Peller M, Jansen O, Mehdorn HM, Buchel C, Siebner HR. (2006). A functional endophenotype for sexual orientation in humans. Neuroimage 33:825-833.

Tomassini V, Jbabdi S, Klein JC, Behrens TE, Pozzilli C, Matthews PM, Rushworth MF, Johansen-Berg H. (2007). Diffusion-weighted imaging tractography-based parcellation of the human lateral premotor cortex identifies dorsal and ventral subregions with anatomical and functional specializations. J Neurosci. 27:10259-69.

Mirror Neurons and Magical EFT Therapy Bears

Magic Buttons Bear

Emotional Freedom Techniques (EFT) is a form of alternative therapy that

purports to manipulate the body's energy field by tapping on acupuncture points while a specific traumatic memory is focused on, in order to alleviate a psychological problem. Critics have described the theory behind EFT as pseudoscientific and have suggested that any utility stems from its more traditional cognitive components, such as the placebo effect, distraction from negative thoughts, rather than from manipulation of meridians.

EFT, a form of Thought Field Therapy (TFT), has been thoroughly debunked as pseudoscience by the Skeptical Inquirer:

Can We Really Tap Our Problems Away?

. . .EFT is very similar to TFT, except that it employs one simplified and ubiquitous tapping procedure instead of applying different algorithms to treat different problems. On his Web site, [Gary] Craig¹ asserts that Callahan’s reliance on differing algorithms is unnecessary because he has witnessed TFT therapists tap in the wrong order or apply the wrong algorithm to the particular problem and still obtain improvements. Craig’s anecdotal evidence appears to contradict Callahan’s anecdotal evidence. Furthermore, Craig extends his tapping therapy far beyond the realm of mental health, reporting testimonials from individuals who claim to have successfully used EFT to treat everything from autism to warts and various other medical problems with positive results...

A scientifically minded investigator would have then taken Craig’s observations a step further and tested a completely "placebo” algorithm which did not tap on any supposed energy meridians to see if it produced similar results. However, Craig reports that he has never carried out this simple experiment nor does he know of anyone who has. Furthermore, Craig speculates that a placebo algorithm may be impossible because tapping anywhere on the body will affect the body’s energy meridians. This position conveniently renders Craig’s theory unfalsifiable and therefore outside the realm of science.

EFT therapists can act as surrogates, tapping on themselves to cure the problems of others. But even more fun than that, why use yourself as a surrogate when you can tap on a cute magical teddy bear? Really and truly? According to Craig:

It is easily explainable in spiritual terms (we are all connected) and through the findings of quantum physics.

But it would behoove him to read a physics textbook, as well as the Skeptic's Dictionary: "This is the golden rule for New Age quacks: when in doubt, quote Einstein and mention quantum physics... What Gary forgets to tell us is that the so-called subtle energy of acupuncture has nothing in common with the energy in E=mc². When you unblock that kind of energy you get nuclear weapons or power, not miraculous health cures."

EFT therapists have also resorted to those trendy media favorites -- mirror neurons! -- to explain their quackery:

HOW CAN THE BEARS WORK?

Perhaps one explanation is Mirror Neurons.

It's been shown in scientific experiments that when one animal is doing something such as eating a banana, another animal who is merely watching will have the same neurons lighting up in their brains as the animal who is doing the activity.

Likewise, in tests done with acupuncture, when needles are being inserted into points on one person, the same points are lighting up on a person who is only observing. In the case of the Magical Bears, we might conclude that when you are tapping on the bear, as you tap, your points would be lighting up as well.

hat tip: AA

Everyone knows what mirror neurons are, those darlings of the pop neuroscience world. First observed in the ventral premotor area F5 of macaque monkeys, mirror neurons increase their rate of firing when the animal performs an action, and when the animal watches someone else perform the action (Rizzolati et al, 1996). These "monkey see, monkey do" neurons have taken on a life far beyond their originally postulated role in imitation. However, not everyone believes that mirror neurons can account for all aspects of human language, culture, and social cognition -- from empathy to altruism to autism to aesthetics to

certain listeners' misattribution of anger in the music of avant garde jazz saxophonists (Gridley & Hoff, 2006)

-- as explained by Alison Gopnik [see also The Neurocritic, Mixing Memory, Neurofuture, et al.]:

The idea that these particular cells might underlie a fundamental human impulse [altruism] reflects the emergence of a new scientific myth. Like a traditional myth, it captures intuitions about the human condition through vivid metaphors.

As long-time readers might know, mirror neurons have been a popular topic of ridicule throughout the entire four year history of this blog. For your celebratory reading pleasure, here's The Neurocritic's mirror neuron œuvre:

Neuromarketing and "the Super Bowl Brain Scans"

Neurofeedback in Autism

Spindle Neurons: The Next New Thing?

An "Endophenotype" For Sexual Orientation?

Mirror Neurons Control The Universe

Mirror Neurons in Primary Motor Cortex?

Mirror Neurons Control Hard-ons?

Waves of Mu

Spanner or Sex Object?

I Feel Your Pain, I REALLY Do: Synaesthesia for Another's Pain


Footnote

¹ "Gary Craig is not a licensed health professional and offers EFT as an ordained minister and as a personal performance coach. Please consult qualified health practitioners regarding your use of EFT."

Twitticism: "Mirror neurons can explain everything. We can all go home now."

Mirror Neurons in Primary Motor Cortex?

The mirror neurons, it would seem, dissolve the barrier between self and others. I call them "empathy neurons" or "Dalai Llama neurons".

-- MIRROR NEURONS AND THE BRAIN IN THE VAT
by V.S. Ramachandran

Everyone knows what mirror neurons are, those darlings of the pop neuroscience world. First observed in the ventral premotor area F5 of macaque monkeys, mirror neurons increase their rate of firing when the animal performs an action, and when the animal watches someone else perform the action (Rizzolati et al, 1996). These "monkey see, monkey do" neurons have taken on a life far beyond their originally postulated role in imitation. However, not everyone believes that mirror neurons can account for all aspects of human language, culture, and social cognition -- from empathy to altruism to autism to aesthetics to

certain listeners' misattribution of anger in the music of avant garde jazz saxophonists (Gridley & Hoff, 2006)

-- as explained by Alison Gopnik [see also The Neurocritic, Mixing Memory, Neurofuture, et al.]:

The idea that these particular cells might underlie a fundamental human impulse [altruism] reflects the emergence of a new scientific myth. Like a traditional myth, it captures intuitions about the human condition through vivid metaphors.

An intriguing new study in the Journal of Neuroscience (Tkach et al., 2007) describes neuronal activity in the primary motor cortex (MI, also called M1) and dorsal premotor cortex of monkeys that looks an awful lot like that of mirror neurons, heretofore confined to ventral premotor cortex and the inferior parietal lobe. The authors conclude that

congruence between observation and action is a general feature of the motor system, even outside of canonical "mirror" areas.

Why is this so interesting? Primarily because of what's going on in M1. If [some] cells there show similar activity during both the execution and observation of actions, what's preventing the arm from moving in the latter case?

If our interpretation of this phenomenon is correct and the monkeys are generating covert motor commands during observation that are congruent with the commands generated during the behavior itself, a natural question is how the dissociation between motor cortical modulation and action occurs. One possibility is that the motor cortical activity we observe is being actively gated by other cortical areas. Results from human EEG studies along with our LFP results suggest that an increase in power in the beta range is associated with inhibition of the excitatory state of the motor cortex (Gilbertson et al., 2005). There is some clinical evidence regarding the origin of this inhibition in patients with frontal lobe damage that exhibit "unwilled" automatic movements (Archibald et al., 2001). These clinical studies suggest that the prefrontal, anterior cingulate, and supplementary motor cortices may contribute the necessary inhibition to prevent triggering of movement commands realized in activated motor and premotor cortical areas. Another possibility is that the motor cortex is part of a more distributed network responsible for movement. Therefore, motor cortical activity alone may not be sufficient to elicit action. Without knowing more about the functional roles of the cells from which we are recording, it is difficult to say anything further about the mechanisms intervening between stimulus and response during the observation phase of the experiment.

In the end, we return to the question, "What's so special about mirror neurons?" We know virtually nothing about the morphological properties of these magical cells (unlike their media cousins, the spindle neurons), so the answer awaits another day (and results from some highly impractical experiments).

References

Gridley MC, Hoff R. (2006). Do mirror neurons explain misattribution of emotions in music? Percept Mot Skills 102:600-2.

Rizzolatti G, Fadiga L, Gallese V, Fogassi L. (1996). Premotor cortex and the recognition of motor actions. Cog Brain Res. 3:131-41.

Tkach D, Reimer J, Hatsopoulos NG. (2007). Congruent activity during action and action observation in motor cortex. J Neurosci. 27:13241-50.

A variety of studies have shown that motor cortical areas can be activated by observation of familiar actions. Here, we describe single-neuron responses in monkey primary motor (MI) and dorsal premotor (PMd) cortices during passive observation and execution of a familiar task. We show that the spiking modulation, preferred directions, and encoded information of cells in MI and PMd remain consistent during both observation and movement. Furthermore, we find that the presence of a visual target is necessary to elicit this congruent neural activity during observation. These findings along with results from our analysis of the oscillatory power in the beta frequency of the local field potential are consistent with previous imaging and EEG studies that have suggested that congruence between observation and action is a general feature of the motor system, even outside of canonical "mirror" areas. Such congruent activity has proposed relevance to motor learning, mimicry, and communication and has practical applications for the development of motor-cortical neuroprostheses in paralyzed patients.

Spindle Neurons in Macaques?

Spindle neurons, or Von Economo neurons (VENs), are a unique type of large, bipolar neuron found primarily in layer Vb in the anterior cingulate cortex and the frontoinsular cortex of humans.¹ In 1999, Nimchinsky and colleagues discovered that among the 28 nonhuman primate species they examined, only great apes had VENs [see Spindle Neurons: The Next New Thing?].

Spindle neurons are also seen in humpback, fin, sperm, and killer whales (Hof & Van der Gucht, 2007), elephants (Hakeem et al., 2009), and cetaceans such as the bottlenose dolphin, Risso’s dolphin, and the beluga whale (Butti et al., 2009).

Because VENs are only found in large-brained, highly evolved social species, and are potentially implicated in certain neurological and psychiatric disorders, their hypothesized functions include empathy, conscious awareness, and self-referential processing. A 2011 review by Allman and colleagues reiterated that only great apes (bonobos, chimpanzees, gorillas, orangutans) have VENs and suggested they...

...may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI [frontoinsular cortex] and LA [limbic anterior area] to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of frontotemporal dementia (FTD) implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging.

VENs: Not Only for Great Apes Any More!

But now, a new study has identified these special neurons in the insular cortex of macaque monkeys (Evrard et al., 2012).


Figure 1 (Evrard et al., 2012). The Von Economo Neuron Is Present in Layer 5b in a Restricted Portion of the Agranular Anterior Insula in the Macaque Monkey (A) High-magnification photomicrographs demonstrating the identical morphology of the macaque and human VENs. Scale bar represents 25 μm.


Why weren't they found in the earlier studies that looked for them?

Three reasons: (1) they're a lot smaller in monkeys; (2) they're more fragile in monkeys; and (3) they're confined to a more limited anatomical region.

First, the large human VENs unambiguously stand out at low microscope magnifications. Searching for relatively smaller VENs among the densely packed cell population in layer 5 in the monkey required the highest microscope magnification, which would be unusual for anyone accustomed to examining the more obvious VENs in hominids. Second, the cytoskeletal matrix of the small monkey VENs might be more fragile during histological processing than that of the larger human VENs. ... Third, in the major prior study, the number of VENs in humans and great apes was counted in consecutive sections that were apparently spaced at 1 mm intervals ... such a sampling paradigm would likely have been inadequate for the identification of VENs within the small VEN-containing region of the ventral AAI that measures ∼2 × 2 × 1 mm³ in macaques.

The authors pointed out a major advantage of their new discovery, namely that more invasive studies are now possible (i.e., you can't do single cell neurophysiology in dolphins or bonobos).

But wait... are they really VENs?

The morphology, size, laminar distribution, and proportional distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN.

Allman, Hof, and colleagues might have something more to say on the matter, based on their earlier findings (e.g., Allman et al., 2011):

The VENs are illustrated at higher magnification in Figure 3, which shows that they have very similar morphology in the great apes and humans. In primates, the VENs are present in FI only in great apes and humans. This is the same taxonomic distribution as was found for the VENs in LA, which suggests that the VENs emerged as a specialized neuron type in the common ancestor of great apes and humans.

Figure 3 (Allman et al., 2011). VENs in area FI of humans and great apes.


The new paper concedes that:

The presence of VENs in the macaque does not discredit prior evidence for a crucial role of the VENs and AIC in the emergence of self-awareness and social cognition in humans (Craig, 2009; Allman et al., 2011). VENs in humans appear to be disproportionally slightly larger than in macaques (see above); they may also have an enhanced immunopositivity (and perhaps gene expression) for proteins that are typically involved in homeostasis, which perhaps favors higher interoceptive sensitivity.

Are they confined to the anterior insula in macaques? No, VENs were also found in the ACC, but that will be reported separately (a lesson for all you junior scientists).

Now that they've been found in monkeys [and can be studied physiologically], will spindle neurons finally catch up with their more glamorous elder cousins, the mirror neurons? Are they really the next new thing? Six years ago, I pondered these points:

Somehow, the "spindle neuron" meme hasn't caught on like the "mirror neuron" meme. Is it because spindle neurons have been only been described anatomically (not physiologically), while the reverse is true for mirror neurons? Anatomically speaking, do we know much about mirror neurons?

Evrard, Forro, and Logothetis are all over it:

...invasive studies of their organization, hodology, and physiology could provide significant insights into the evolutionary basis for self-awareness and empathy in humans. Regarding the latter, it would be particularly interesting to examine whether the VENs share functional similarities with the “mirror” neurons of the ventral premotor cortex (Gallese et al., 2004).

Finally, a commentary in Neuron by Critchley and Seth (2012) wonders if studies of the macaque insula will reveal the neural mechanisms of self-referential processes underlying conscious awareness. If VENs indeed mediate self-referential processing, then they were largely involved in writing this post.


More Reading

Spindle Neurons: The Next New Thing?

Spindle Neurons in Humpback Whales

Spindle Neurons and Frontotemporal Dementia

Spindle Neurons and Science Writing

Spindle Neurons in Elephants and Dolphins: Convergent Evolution in Large-Brained Mammals?


Footnotes

¹ The VENs and other large pyramidal cells in cortical layer V are projection neurons that provide output to more distant regions.


References

Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, Park S, Goubert V, Hof PR. (2011). The von Economo neurons in the frontoinsular and anterior cingulate cortex. Ann NY Acad Sci. 1225:59-71.

Butti, C., Sherwood, C., Hakeem, A., Allman, J., & Hof, P. (2009). Total number and volume of Von Economo neurons in the cerebral cortex of cetaceans. Journal of Comparative Neurology 515:243-259.

Evrard, H., Forro, T., & Logothetis, N. (2012). Von Economo Neurons in the Anterior Insula of the Macaque Monkey. Neuron, 74 (3), 482-489 DOI: 10.1016/j.neuron.2012.03.003

Hakeem, A., Sherwood, C., Bonar, C., Butti, C., Hof, P., & Allman, J. (2009). Von Economo Neurons in the Elephant Brain. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology 292:242-248.

Hof PR, Van Der Gucht E. (2007). Structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae). Anatom Rec Part A, 290:1-31.

Nimchinsky EA, Gilissen E, Allman JM, Perl DP, Erwin JM, Hof PR. (1999). A neuronal morphologic type unique to humans and great apes. Proc Natl Acad Sci 96:5268-73.

Mirror Neuron Death March

Above image: Jim Peters almost wins the marathon Vancouver, 7 August 1954, with mirror neurons by Rizzolatti & Craighero (2004).

Greg Hickok at Talking Brains has a series of posts dismantling the mirror neuron theory of action understanding. Actually, he lets one of the leading researchers in the field, Giacomo Rizzolatti [and his coauthor] dismantle the theory himself in a recent review paper (Rizzolatti & Sinigaglia, 2010). Greg points out the inconsistencies in the NRN article...

So, mirror neurons, those cells that fire during specific actions such as grasping-with-the-hand and while watching the same specific action -- the very cells that got everyone SO excited -- are not involved in action understanding. Rather, according to R&S, action understanding is achieved by cells that do not code for actions at all, but something higher level, goals/intentions.

It's worth noting that R&S directly contradict themselves in the sidebar definition of "Mirror-based action understanding":

The comprehension of an observed action based on the activation of a motor programme in the observer’s brain. p. 265

A motor program presumably controls a specific action, such as grasping-with-the-hand, not an action-independent goal or intention.

...and also the problems with promoting an unfalsifiable theory:

I think the mirror neuron folks have a serious problem on their hands: there is apparently no empirical result that can falsify the theory. If a mirror neuron shows up in an unexpected place, it is a new part of the mirror system. If a mirror neuron's activity dissociates from action understanding, it was not coding understanding at that moment. If damage to the motor system doesn't disrupt understanding, it is because that part of the motor system isn't mirroring.

As another long-time mirror neuron skeptic, I highly recommend this series:

Mirror Neurons - The unfalsifiable theory

Mirror neurons support action understanding -- "from the inside"?

Self-destruction of the mirror neuron theory of action understanding

Reference

Rizzolatti, G. & Sinigaglia, C. (2010). The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations. Nature Reviews Neuroscience, 11 (4), 264-274.

Everybody in Mirror Neurons!

See Spindle Neurons: The Next New Thing?