OK, I'm back in Philadelphia and my copy of Louann Brizendine's The Male Brain has arrived. I still haven't had time to read it, but I promised to look up the business about the dorsal premammillary nucleus, so here goes.
You'll recall that Dr. Brizendine's opinion piece at cnn.com ("Love, sex, and the male brain", 3/24/2010) asserted that
Our brains are mostly alike. We are the same species, after all. But the differences can sometimes make it seem like we are worlds apart.
The "defend your turf" area — dorsal premammillary nucleus — is larger in the male brain and contains special circuits to detect territorial challenges by other males. And his amygdala, the alarm system for threats, fear and danger is also larger in men. These brain differences make men more alert than women to potential turf threats.
And Vaughan Bell at Mind Hacks countered that
Male and female humans are indeed the same species, but we are not a species which has a dorsal premammillary nucleus because it's only been identified in the rat.
Furthermore, there is no reliable evidence that amygdala size differs between the sexes in humans and a recent study that looked specifically at this issue found no difference.
His link with respect to amygdala size was specific (J. Brabec et al., "Volumetry of the human amygdala – An anatomical study", Psychiatry Res 2010), and completely contradicted Brizendine's assertion.
But in the case of the dorsal premammillary nucleus, Vaughan could give only a link to a PubMed search, which might perhaps have missed something; so I wondered what specific support Brizendine might have cited in the book for this point.
Indeed, The Male Brain displays the same impressive flourish of endnotes and references as The Female Brain did. It has 135 pages of text, 41 pages of endnotes, and 83 pages of references. I'll be interested to see whether the notes and references are related to the claims in the text in the same way. In several tedious posts (e.g. here, here and here), I followed up the notes and references behind specific claims in The Female Brain, and found a surprising lack of relevant connection.
I'm not sure how much more of such sleuthing I've got the energy for, but I promised to check out that dorsal premammillary nucleus, so here goes. (Regular readers won't be surprised to learn that this turns out to be another beautiful example of Explanatory Neurophilia.)
The Male Brain's index gives us these page references for dorsal premammillary nucleus:
emotional lives of men and, 110, 111, 170-71
function of, xv
Pages xv-xvi are a picture of "The Male Brain" with ten areas singled out for attention. The header says that
Scientists think of brain areas like the ACC, TPJ, and RCZ ad being "hubs" of brain activation, sending electrical signals to other areas of the brain, causing behaviors to occur or not occur.
The third of the ten key areas (maybe more later on the nine others) is listed this way:
3. DORSAL PREMAMMILLARY NUCLEUS (DPN): The defend-your-turf area, it lies deep inside the hypothalamus and contains the circuitry for a male's instinctive one-upmanship, territorial defense, fear, and aggression. It's larger in males than in females and contains special circuits to detect territorial challenges by other males, making men more sensitive to potential turf threats.
There are no endnotes for this section. A quick check of the literature reveals that the DPN in rats is involved in a number of things that have nothing to do with intra-species turf defense, e.g. as described in D. Caroline Blanchard et al., "Dorsal premammillary nucleus differentially modulates defensive behaviors induced by different threat stimuli in rats", Neuroscience Letters 345:145-148, 2003:
Lesions of the dorsal premammillary nucleus (PMd) have been reported to produce dramatic reductions in responsivity of rats to a live cat. Such lesions provide a means of analyzing the potentially differential neural systems involved in different defensive behaviors, and the relationship between these systems and concepts such as anxiety. Rats with bilateral electrolytic lesions of the PMd were run in an elevated plus maze (EPM), exposed first to cat odor and then to a live cat, and assessed for postshock freezing and locomotion. PMd lesions produced a dramatic reduction in freezing, avoidance, and stretch attend to the cat odor stimulus, and reduction in freezing, with greater activity, and enhanced stretch approach to cat exposure. However, PMd lesions had minimal effects in the EPM, and postshock freezing scores were unchanged. These results confirm earlier findings of reduced defensiveness of PMd-lesioned rats to a cat, extending the pattern of reduced defensiveness to cat odor stimuli as well, but also suggest that such lesions have few effects on nonolfactory threat stimuli.
In other words, the DPN is involved in rats' (passive) defensive responses to the presence of a cat, or even just to cat odor, but not to other sorts of threats such as the open arms of a maze, or an electric shock to the foot, where odor is not involved. Thus the DPN is more (and also less) than "the defend-your-turf area" in rats — it responds to predator threats as well as threats from dominant conspecifics, but it's apparently not involved in more active or aggressive forms of defense. Who knows what its homologue's functions are in humans – but presumably the mediation of instinctive "freezing, avoidance, and stretch" responses to cat odor are not among them.
Page 110 of The Male Brain tells us:
Evolutionary biologists suggest that behaviors like bluffing, posturing, and fighting have evolved to protect males, especially from opponents within their own species. Instinctive male-male competition and hierarchical fighting is driven by both hormones and brain circuits. A special area in the male brain's hypothalamus, the dorsal premammillary nucleus, or DPN, has been discovered, in rats, to contain circuitry for this instinctive one-upmanship. In humans, this one-upmanship and drive for status-seeking is found in men worldwide; it's not just a habit or a cultural tradition but more like a design feature of the male brain.
Here (unlike in the earlier passage) the DPN size business is explicitly linked to research on rat brains, and the connection to human males is made only by implication.
The endnotes (p. 170) give us this:
110 circuitry for this instinctive one-upmanship: Motta 2009 found an area in the male brain's hypothalamus, called the DPN, is activated for instinctive one-upmanship in male rats for territory protection against higher-ranking males.
That's S.C. Motta and M. Goto, "Dissecting the brain's fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders", PNAS 106(12):4870-75, 2009.
As this study notes, lesion studies had previously established that (in rats) "the site most responsive to predatory threats" (specifically, cats) is "the tiny dorsal premammillary nucleus (PMD)", though other parts of the hypothalamus are also involved. Motta and Goto's contribution:
The experiments reported here were designed to test the hypothesis that the hypothalamus also plays a critical role in the processing and expression of fear responses to another natural danger—a dominant conspecific. For this, hypothalamic activation in response to a predator or a dominant conspecific was compared and it was shown that the PMD is critical for fear expression in both situations, supporting a critical role for the hypothalamus in both responses. Furthermore, despite similar behavior patterns displayed in both threatening situations, predator and dominant conspecific threats are processed by differentiable components of the fear system.
The dependent variable that they looked at was not "activation" in the sense of direct measures of electrical activity, but rather upregulation of the protein product Fos. Interestingly, the PMD (their acronym for the dorsal premammillary nucleus) is the part of the hypothalamus most similarly affected by the threats posed by predators and by dominant conspecifics:
Hypothalamic patterns of neuronal activation are thus strikingly different in animals exposed to a natural predator or a dominant conspecific, although they are not entirely separate. In particular, the PMD was clearly activated in both experimental groups. Careful anatomical inspection indicates, however, that PMD activation patterns are not identical in the 2 groups. Cell count analysis confirms that exposure to a predator or a dominant conspecific massively induces Fos upregulation in the PMD (F3,21 = 129.9, P < 0.0001) and that, whereas predator exposure upregulation is centered in ventrolateral regions of the PMD (PMDvl), upregulation following exposure to a conspecific resident is centered in dorsomedial regions of the nucleus.
So what we have — in male rats — is that the DPN is activated by threats from cats and from dominant conspecifics; and that the (overlapping) effects of these two threats are centered in slightly different parts of the ("tiny") DPN, with the effect of the alpha rats being centered in dorsomedial (as opposed to ventrolateral) regions.
This is a long ways from identifying the DPN, even in rats, as "the defend-your-turf area" that "contains the circuitry for a male's instinctive one-upmanship, territorial defense, fear, and aggression", especially because the rat-response involved (to both predators and dominant conspecifics) is "freezing" or other passive defense reactions, not "boxing" or other aggressive or active defense behaviors, much less the general pattern of "bluffing, posturing, and fighting" that Brizendine attributes to this brain region.
(By the way, I'm also somewhat taken aback by the unsupported assertion that "drive for status-seeking" is "a design feature of the male brain", given years of science and fiction suggesting — if anything — the opposite sexual stereotype. For a survey of one set of issues in the linguistic area, see Elizabeth Gordon, "Sex, speech and stereotypes: Why women use prestige speech forms more than men", Language in Society 26:47-63, 1997. As a crude check on the validity of the cross-cultural concept here, a search on Google Scholar for male status-seeking returns 2,220 items, while a search for female status-seeking returns 2,050 — a random example being "Empirical Tests of Status Consumption: Evidence from Women's Cosmetics".)
Page 111 tells us the story of "Neil", a patient who is anxious about the fact that the president of his firm has decided to retire:
If we could peek back into Neil's brain in this atmosphere of unstable hierarchy, we'd see what was causing his emotional roller-coaster ride. When he thought his prospects for VP looked promising, we'd see his brain area for anticipating rewards activating, and he'd feel good. But when he thought George might get the promotion, we'd see his territoriality circuits in the DPN activating, and he'd feel haunted by the threat of losing face and forfeiting his place in the hierarchy.
Assuming that he's a rat, that is, and that he's "freezing" because a dominant rat has entered his cage. (In fact, Neil's turmoil is caused by the fact that the dominant male is leaving the cage, thus putting the status hierarchy in doubt — Brizendine doesn't cite any studies that show DPN activation in rats as a result of status uncertainty.)
There are no new footnotes for this passage — Brizendine has simply transferred some partly-analogous research from rats, where her interpretation is oversimplified and over-interpreted, to men, where we have no idea whatsoever whether Neil's DPN is playing any special role at all in his turmoil, and certainly no idea whether it's playing a sex-specific role.
Pages 170-171: Page 170 contains the note relevant to page 110, discussed above. Page 171 contains notes to pages 112-113 of the text, none of which say anything whatever about the DPN.
So I'm afraid that Vaughan Bell was right — Louann Brizendine's assertions in her CNN piece about the DPN are based entirely on rat research. I think he might have gone too far in asserting that this structure "[has] only been identified in the rat". At least, if I understand Clifford B. Saper, "Hypothalamus", chapter 17 (pp. 513-550) in The Human Nervous System, 2004, there's a homologous region in the human brain (though I can't figure out for sure whether the same name is used). But there seems to be no evidence as to whether its size is sexually differentiated, and what functions it might have.
In another respect, Vaughan didn't go far enough in calling her claims into question, since even if men and women were exactly like male and female rats in the relevant respects, she'd be elevating to the status of "the defend-your-turf area" a brain region that mediates freezing reactions to cat odor (but not non-smell-related threats) and similar passive reactions to (the smell of?) dominant conspecifics.
In thinking about these things, I recommend taking a look at Geert de Vries & Per Södersten, "Sex differences in the brain: The relation between structure and function", Hormones and Behavior 55(5):589-596, 2009. Their abstract:
In the fifty years since the organizational hypothesis was proposed, many sex differences have been found in behavior as well as structure of the brain that depend on the organizational effects of gonadal hormones early in development. Remarkably, in most cases we do not understand how the two are related. This paper makes the case that overstating the magnitude or constancy of sex differences in behavior and too narrowly interpreting the functional consequences of structural differences are significant roadblocks in resolving this issue.
They close with this observation on "The dual function hypothesis":
In prairie voles, the presence of a sex difference in the brain clearly does not correlate with the size of a sex difference in behavior. The species with the largest sex difference in VP [vasopressin] innervation reported to date shows some of the least conspicuous sex differences in social behavior. Apparently, the sex difference in VP can cause as well as prevent sex difference in social behavior. Because there is no reason that this dual function is VP's prerogative, we suggested that in general sex differences in brain structure may cause as well as prevent sex differences in specific behaviors or centrally regulated functions. This dual function hypothesis is perfectly testable. To take the VP system as an example, one would predict in the former case, that blocking VP neurotransmission would blunt or eliminate sex differences and in the latter case that the same treatment would cause a sex difference that wasn't there before. In fact, such tests have already been done; treatment with a VP antagonist blocked social recognition memory in male but not in female rats, thereby creating a new sex difference. Related to this, the V1a receptor knock-out mouse has a behavioral phenotype in males but not in females, exactly what one would predict for a system that is more important for a function in one sex than in the other.