Crossed Wires

From similar sets of neuroimaging data, researchers are reaching different conclusions about whether brain wiring differs between men and women.

By | January 16, 2015

FLICKR, WINDELL OSKAYIn a brain-imaging study published in PNAS in December 2013, scientists reported significant differences in brain connectivity patterns between men and women. If confirmed, their finding would overturn the widespread assumption among neuroscientists that sex doesn’t matter when it comes to brain anatomy and function. What’s more, the authors—a group co-led by Ruben Gur at the University of Pennsylvania—suggested that such wiring differences could give rise to behavioral differences between the sexes.

“Detailed connectome maps of the brain will not only help us understand the differences between how men and women think, but it will also give us more insight into the roots of neurological disorders, which are often sex-related,” Gur said in a statement.

But it wasn’t long before the results were called into question. Several researchers pointed out that the authors failed to include data on effect size, making it difficult to verify claims about “fundamental” differences in brain wiring between the sexes. Some critics also argued that Gur and colleagues had ignored other factors that could have accounted for the results—gendered experiences like hobbies or study subjects, say, or brain size. Still others accused the authors of having served up untested stereotype-based speculation on how such wiring differences could affect behavior.

Then, in November 2014, Jürgen Hänggi at the University of Zurich and his colleagues published a study in Frontiers of Human Neuroscience demonstrating that the wiring differences observed by Gur’s team were driven by differences in brain size rather than sex.

To further muddy the waters, researchers who were not involved in either study offer conflicting views on the links among sex, brain size, and the human connectome.

To neurobiologist Larry Cahill’s mind, sex is the biggest factor driving brain size, so even if connectivity differs according to brain size, there is still a strong sex influence, on average, on connectivity patterns. “While we can and should debate what these findings mean,” said Cahill, a professor at the University of California, Irvine, “the findings leave little doubt that there exist striking differences in the ways in which the brains of women, on average, and men, on average, are wired.”

But Cordelia Fine, a neuropsychologist at the University of Melbourne and author of Delusions of Gender: The Real Science Behind Sex Differences, said that “it’s an important and plausible possibility that these wiring differences are largely or entirely an effect of brain size, and may have little bearing on our understanding of sex differences in behavior.”

Stats and significance

For their study, Gur and his colleagues used a version of MRI called diffusion tensor imaging (DTI) to construct brain-wiring maps of 949 people (428 male and 521 female) aged 8 to 22. Their analysis demonstrated that, on average, male brains have more connections within each hemisphere than do females brains, whereas female brains tend to have more connections across the two hemispheres. This led the researchers to write that their results “reveal fundamental sex differences in the structural architecture of the human brain.”

As commenters pointed out on the post-publication peer review website PubPeer and elsewhere, the paper did not include estimates of effect size to substantiate such claims. “They report finding significant differences between the sexes, but don’t show the statistics that allow the reader to evaluate the size of any sex difference against other factors such as age or individual variability,” wrote Tom Stafford of the University of Sheffield, at The Conversation. “This matters because you can have a statistically significant difference which isn’t practically meaningful.”

In response, Gur said that one could estimate effect size from the data presented. Indeed, Gerard Ridgeway, who works on statistical analysis of brain-imaging data at the University of Oxford but was not involved in the study, did just that. He calculated an approximate effect size (Cohen’s d = 0.48, compared to 1.72 for height difference) that was “not consistent with the idea that men’s and women’s brains are fundamentally ‘wired’ differently,” Ridgeway wrote at Figshare. Instead, he suggested, connections in the brains of men and women may display subtle differences on average, which can be statistically significant with a large sample size.

Even so, Ridgeway acknowledged that there are no objective thresholds for “small” or “large” effects. And Cahill argued that even small effect sizes can be important. “It’s incorrect to think the only statistically significant findings we have to worry about are ones with large effect sizes,” said Cahill. “The vast majority of biomedical research has relied on statistical significance, independent of effect size, and that’s perfectly justifiable.”

Size not sex?

Another criticism of the 2013 PNAS paper was that Gur and colleagues didn’t rule out alternative explanations for the brain wiring differences. “The authors paid no attention—either empirical or conceptual—to the possible role of gendered experiences . . . in female/male differences in brain or behavior,” Melbourne’s Fine wrote in an e-mail to The Scientist.

Further, she added, “the authors didn’t consider that their findings reflect different wiring solutions between larger and smaller brains, rather than sex differences per se.” Zurich’s Hänggi and colleagues had also suspected as much. When a comment they submitted to PNAS detailing this alternative explanation was rejected, the researchers instead published a paper in Frontiers.

To test the hypothesis that differences in brain wiring are a function of brain size, Hänggi and colleagues used DTI to examine connectivity patterns in 138 human brains (69 male and 69 female). They found a clear link between brain size and wiring pattern: intrahemispheric connectivity was stronger in larger brains, the researchers found, irrespective of sex.

What’s more, Hänggi’s team was able to replicate Gur’s finding—a correlation between sex and brain wiring pattern—in a random subsample including only 27 male and 27 female brains. Then, to investigate the effect of sex differences independent of brain size, the researchers compared the size-matched brains of 27 men and 27 women. In groups with equal brain sizes, there was no significant correlation between sex and connectivity pattern. “The apparent sex effect disappeared,” said Hänggi.

Conflicting views

Gur does not agree. “I don’t think their own data support their conclusions,” he said of Hänggi’s results. “With such a small sample, to claim that they can explain all the differences in connectivity by brain volume, and to do that by picking all sorts of subsamples, makes no sense.” Gur added that his group had covaried for brain size in their original analysis, finding that the sex effect remained. “It attenuated, but it did not go away,” he said of this secondary analysis, which the researchers did not include in the manuscript they submitted to PNAS.

UC Irvine’s Cahill added that even if Hänggi’s results stand up, they don’t negate the finding that there is a difference in wiring patterns in the brains of men, on average, compared to those of women, on average. “What is the single largest factor we have that distinguishes the big-brained and small-brained groups [in Hänggi’s study]?” he asked. “It’s sex. So even if we grant that Hänggi et al. are correct that brain connectivity differs according to brain size, we still have the same sex influence, on average.”

For Cahill, Hänggi and colleagues are operating under a false assumption of what constitutes a sex difference. Of course, some women will have bigger brains than some men, just as some women are taller than some men, but on average men are taller than women, and have larger brains. “It’s not a binary difference, like penis and vagina,” said Cahill. “That’s why I prefer the term ‘sex influence.’ Different brain size is a consequence of sex, so—directly or indirectly—the difference in brain connectivity is influenced by sex.”

But Hänggi maintained that brain size trumps sex in its influence on brain wiring. “Assuming that brain sex and brain size are highly correlated, similar effect sizes should have been reported in both studies,” he wrote in a follow-up e-mail. “However, the strongest effect size reported by Gur and colleagues, who investigated 949 subjects, was approximately d = 0.482. We investigated only 138 subjects, but we found effect sizes [for brain size] that were twice or three times times larger (d = 1.65).”

If Hänggi is right, and what was presented as a sex effect is indeed a brain-size effect, Fine noted that this finding would have implications for the work of neuroscientists trying to explain behavioral differences between the sexes. “Unless we have a reason to think that, due to their different brain connectivity, larger-brained men differ psychologically to smaller-brained men, and ditto for females, it no longer seems likely to be of profound behavioral importance that, overall, females and males have different patterns of connectivity,” she said.

Editor’s note (January 19): This article has been updated to clarify Cordelia Fine’s position with the addition of a quote in the seventh paragraph.

Add a Comment

Avatar of: You

You

Processing...
Processing...

Sign In with your LabX Media Group Passport to leave a comment

Not a member? Register Now!

LabX Media Group Passport Logo

Comments

Avatar of: BrainSize

BrainSize

Posts: 1

January 16, 2015

Dear reader

I would like to add some further empirical evidence clearly favoring brain size over sex.

In the above mentioned article, Prof. Gur said:

"With such a small sample, to claim that they can explain all the differences in connectivity by brain volume, and to do that by picking all sorts of subsamples, makes no sense.”

However, the results these "small non-sense subsamples" provided are very interesting.

1. If brain sex and brain size are the same thing, it is difficult to explain

(i) why we have also found the connectivity patter under question within sex-specific groups (i.e., when we compared small-brained women with large-brained women and small-brained men with large-brained men) and

(ii) why this effect disappears when men and women were matched (balanced) for brain size.

2. The strength of the effect under question can be modulated by brain size.

(i) When we compared small-brained men with large-brained women, who did not significantly differ in brain size, the effect disappears entirely.

(ii) In sharp contrast, our extreme group comparison compared small-brained women with large-brained men, the brain size of whom differed massively, the effect under question becomes much stronger.

3. Why can the connectivity pattern under question also be found across mammals (from the mouse to the elephant) when it is mainly driven by sex and not by brain size?

In my opinion, the findings of the analyses with these "small non-sense subsamples" are highly convincing and suggest that the effect under question is really driven by brain size and not by sex per se. Therefore, our results clearly contradicting the conclusions drawn by the representatives of the sex hypothesis.

Avatar of: Neurona

Neurona

Posts: 60

January 19, 2015

With all due respect, Dr. Cahill errs very seriously when he refers to penis and vagina as a "binary difference".  The proper comparison is penis and clitoris, where the same embryonic tissues forms different sized phalluses.  

Avatar of: sexyneuron

sexyneuron

Posts: 1

January 20, 2015

Although entries like this one are needed to counteract the wide publicity that studies like this one receive from the press, I must say that this is not a big surprise ...  In fact, many "dramatic" sex differences turn out to be rather small when effect sizes are calculated and not a few vanish when metaanalysis pull together the results of various studies. That's, for example, the case of the often-cited differences on the corpus callossum (for a metaanalysis, see Bishop & Wahlsten Neuroscience and BiobehavioralReviews,Vol. 21, No. 5, pp. 581-601, 1997. 

(By the way, I agree with the comments on the other two posts)

 

Avatar of: N K Mishra

N K Mishra

Posts: 58

January 25, 2015

Behavioural differences between the two sexes are more deeply ingrained. These may be termed tertiary as apposed to primary and secondary.There are numerous variables for differential wiring.

Avatar of: PRice

PRice

Posts: 9

February 15, 2015

At the risk of wading into a quagmire, it’s hard to take this study’s findings seriously, that there are new and significant hardwired differences in human male and female brains in additional to what we already knew, because the authors do not explain all the factors involved in why they found what they did.

For example, can we raise kids in our culture along typical gender roles and biases, then at ages 12-14, say that the differences in their brains are solely due to their genders?

To do so would be to ignore what is known about epigenetic and environmental influences in shaping the brain.

http://surfaceyourrealself.com/2015/02/15/problematic-research-on-hardwired-differences-in-human-male-and-female-brains-surfaceyourrealself/

Avatar of: Growly

Growly

Posts: 2

August 10, 2015

Just an observation here. Aren't scientific studies supposed to be dispassionate, clinical observations? Yet there seems to be a strong irrational, emotional response to the idea that there are differences in the brain structures between the 2 genders. I think everyone should take a step back and ask why that is? Why is there such strong resistance to the idea?

I'm not saying it shouldn't be retested and challenged. That is also a scientific process, so challenging it is a routine requirement. But there does seem to be some sort of emotional resistance to the notion, with theories of brain size and gender programming being preferred; anything in fact, rather than a gender difference. What is everyone so afraid of?

Avatar of: Growly

Growly

Posts: 2

August 10, 2015

Just an observation here. Aren't scientific studies supposed to be dispassionate, clinical observations? Yet there seems to be a strong irrational, emotional response to the idea that there are differences in the brain structures between the two genders. I think everyone should take a step back and ask why that is? Why is there such strong resistance to the idea?

I'm not saying it shouldn't be retested and challenged. That is also a scientific process, so challenging it is a routine requirement. But there does seem to be some sort of emotional resistance to the notion, with theories of brain size and gender programming being preferred; anything in fact, rather than a gender difference. What is everyone so afraid of?

Popular Now

  1. Top 10 Innovations 2016
    Features Top 10 Innovations 2016

    This year’s list of winners celebrates both large leaps and small (but important) steps in life science technology.

  2. Gut Microbes Linked to Neurodegenerative Disease
  3. Pubic Hair Grooming Linked to STI Risk
    The Nutshell Pubic Hair Grooming Linked to STI Risk

    Observational study suggests pubic hair grooming correlates with heightened risk of acquiring sexually transmitted infections, although causation remains unclear.

  4. Naive T Cells Find Homes in Lymphoid Tissue
Rockland