How do I get my statistics right? Solid advice to younger cognitive neuroscientists

Beginning (and also more advanced) cognitive neuroscientists often face the problem of neuroimaging being highly costly (up to even some thousands of dollars/euros per subject) and thus the number of subjects that one can measure end up being rather modest, typically from a few to few tens. Furthermore, modern neuroimaging methods tend to produce a wealth of data per subject, and the poor neuroscientist quickly runs into the problem of having to decide whether and how to conduct corrections for multiple statistical comparisons. Adding to confusion, a cognitive neuroscientist can easily find functional magnetic resonance imaging studies published in notable journals such as Science with as few as eight or even five subjects, and yet run into arguments that his/her "too few" 15 or 20 subjects is a severe problem that results in rejection of the study from a lesser journal.

In his paper that is written with an unusual but highly entertaining ironic tone, Karl Friston (2012) presents the most common lines of critic on statistical analysis of neuroimaging data, provides advice and insights on how to design one's experiment so that it is statistically sound, and how to counter argue the most typical erroneous critic by reviewers. I see this as highly important given the abundance of misunderstandings on statistics that one often runs into when trying to publish findings in the area of neuroimaging (and also other fields of science).

It is important to note that none of the hard work and exciting findings that one obtains really contribute to scientific knowledge until the results have been published in one of the scientific journals. The peer-review process is inarguably the cornerstone of science, and good reviews often help improve the scientific quality of one's publications, but on the other hand delays in publication or rejection of a manuscript (that results in even larger delay in getting published) if based on misunderstanding of statistics especially on part of an expert reviewer, is a highly unfortunate outcome that slows down progress of science.

Reference: Friston K. Ten ironic rules for non-statistical reviewers. NeuroImage (2012) 61: 1300–1310. http://dx.doi.org/10.1016/j.neuroimage.2012.04.018

Midbrain dopamine system triggers shifting of context representations in dorsolateral prefrontal cortex

Shifting quickly and flexibly between different goals that one is pursuing is one of the most amazing of human cognitive skills. For example, running into a friend in the midst of shopping groceries for one’s family in a local store one is able to recall what one had intended to relate to him/her upon seeing that friend. Following lively discussion for several minutes, getting back to the goal of shopping the groceries is flexible and effortless. At the same while that there is this amazing flexibility, one is perseverant and not distracted from pursuing one’s goals by other stimuli and events that are irrelevant to the behavioral goals at hand. It has been proposed that the midbrain dopaminergic system and prefrontal cortical areas underlie this capability to shift between goal directed behaviors, but empirical demonstrations have not been unequivocal.

In their recent study, D’Ardenne et al. (2012) combined transcranial magnetic stimulation and functional magnetic resonance imaging to study the interplay between phasic signals produced by the brain stem dopaminergic system and context representations (aka “cognitive set”) maintained by the prefrontal cortex. The authors observed that transcranial magnetic stimulation of especially the right dorsolateral prefrontal cortex, timed around the presentation of the task context, impaired context-dependent responses more than context-independent responses. Functional magnetic resonance imaging of the ventral tegmental area and substantia nigra further disclosed phasic signals that co-occurred with context shifting events and correlated with phasic signals that were observed in dorsolateral prefrontal cortex.

Together, these experiments provide robust support for the model where phasic (presumably dopaminergic) signals produced by ventral tegmental area and substantia nigra trigger shifting of context representation in the (especially the right) dorsolateral prefrontal cortex. This study also provides a nice example of how transcranial magnetic stimulation can be combined with functional magnetic resonance imaging and behavioral task designs to gain insight into the neural basis of human goal directed behavior.

Reference: D’Ardenne K, Eshel N, Luka J, Lenartowicz A, Nystrom LE, Cohen JD. Role of prefrontal cortex and the midbrain dopamine system in working memory updating. Proc Natl Acad Sci USA (2012) e-publication ahead of print. http://dx.doi.org/10.1073/pnas.1116727109

Enhanced stress reactivity in women after exposure to negative news

Given that stress-related disorders constitute one of the most severe societal and medical problems in modern societies, investigation of the predisposing factors are more than well justified. One potential source of stress is the constant and abundant flow of negative news via the media, including 24-hour TV coverage, internet, and recently also constant access to negative newsfeed through mobile devices such as tablets and smartphones. It has been relatively little explored, however, whether exposure to negative news via the mass media elevates secretion of stress hormones such as cortisol in healthy individuals.

In their recent study, Marin et al. (2012) randomly assigned thirty women and thirty men to groups that were to read twenty-four neutral vs. negative news excerpts lasting for a total of 10 minutes. After that they were all administered the Trier Social Stress Test. Salivary cortisol samples were collected at 10 minute intervals throughout the experimental procedure. A free recall of the news was also performed one day after the experiment. Even though reading the news per se failed to change cortisol levels, cortisol levels were significantly elevated by the Trier Social Stress Test in those women who were first exposed to negative news. Women also remembered the negative news excerpts better than men on the following day.

These findings disclose exposure to negative news as a potential factor that might predispose individuals to elevated stress (especially women, even though similar patterns that however failed to reach statistical significance were also noted in men) and thus in part also enhance the chance for developing stress-related disorders.  The findings show that exposure to negative news modulates the stress reactivity of women to subsequent psychosocial stressor and enhances their memory performance for the negative news. These results point out the importance of better understanding individual and societal reactions to negative information that is brought to people via modern mass media more readily and abundantly than ever before in the history of our species.

Reference: Marin M-F, Morin-Major J-K, Schramek TE, Baupre A, Perna A, Juster R-P, Lupien SJ. There is no news like bad news: women are more remembering and stress reactive after reading real negative news than men. PLoS ONE (2012) 7: e47189. http://dx.doi.org/10.1371/journal.pone.0047189

Brain-state based triggering of target sounds as a novel paradigm in selective attention research

The neural basis selective attention (i.e., how one can select, out of the massive amount of stimuli that constantly bombard one’s senses, the concurrently relevant ones for further processing) is one of the most interesting research questions in cognitive neuroscience. The importance of research on selective attention is further enhanced by the central role that selective attention deficits play in a number of neurological and psychiatric disorders. Dichotic listening is one of the most often-used task paradigms in selective attention research, where subjects are instructed to attend sounds presented to one ear and to ignore sounds presented to the opposite ear. Average neural responses to attended vs. ignored sounds are then compared to disclose neural correlates of selective attention. Fluctuation of the focus of attention over the course of the experiment has been one potential shortcoming of this otherwise excellent paradigm. 

In their recent study, Andermann et al. (2012) detected online the attentional states of experimental subjects and triggered presentation of near-threshold target stimuli based on the presence of correct vs. incorrect attentional state. Specifically, electroencephalogram epochs time-locked to onset of stimuli were first recorded to attended vs. ignored sound streams during a dichotic listening task. These data were then utilized to teach a brain computer interface algorithm to detect high vs. low selective attention states that triggered presentation of the near-threshold targets in the experiment proper. Notably, when the near-threshold target stimuli were presented during estimated correct (i.e., towards the designated ear) vs. incorrect (i.e., fluctuation of attention away from the designated ear) attentional state, the target sounds were detected at a higher rate. Curiously, in the near-threshold target detection task, correct attentional state also resulted in higher number of “illusory percepts” (i.e., a target was detected when none was present). It was also observed that there was considerable fluctuation in the attentional states of the subjects over the course of the experiment.

The strength of this study is that it provides a new type of research paradigm for the investigation of the neural basis of selective attention. More generally, the authors suggest that the brain state-triggered stimulus delivery will enable efficient, statistically tractable studies of rare patterns of ongoing activity in single neurons and distributed neural circuits, and their influence on subsequent behavioral and neural responses.

Reference: Andermann ML, Kauramaki J, Palomaki T, Moore CI, Hari R, Jaaskelainen IP, Sams M. Brain state-triggered stimulus delivery: An efficient tool for probing ongoing brain activity. Open Journal of Neuroscience (2012) 2-5.