No, No, No! How the Brain Processes Negation

Atlantic Fellows Adolfo García and Agustín Ibáñez—along with Mariano Díaz-Rivera and Agustina Birba—share findings from new research about the use of negative language, associated brain activities, and implications for people living with dementia.

Man holding a sign that says "no"

The word 'no': a pathway to study dementia?

No… don’t… won’t… can’t… such useful, ever-present words. There they are, all the time, when you disagree with someone’s opinion, when you decline an invitation, when you stop a toddler from grabbing knife, and so on. These complex functions, including contradiction, rejection, and prohibition, set in motion many social dynamics which shape our daily life. Now, what happens in our brains upon perceiving such words? Which neural circuits do they recruit to achieve such communicative goals? And do these mechanisms differ in people living with dementia?

An interesting theory proposes that negation engages inhibitory mechanisms – that is, the circuits that enable us to interrupt ongoing actions, thoughts, feelings, and impulses. In tasks combining words with physical actions, negative sentences (e.g., Virgil won’t play the drums), compared with affirmative sentences (e.g., Virgil will play the drums), involve distinct changes of the delta band, a brain wave frequency which shows the same pattern when we stop doing an action. Moreover, negative words elicit activity changes in regions of the brain implicated in the suppression of active motoric, cognitive, and affective processes.

Yet, despite its recent growth, evidence for this view has come exclusively from healthy participants. As such, it has failed to achieve a crucial goal for revealing direct links between the brain and behavior: the detection of distinct alterations in patients with different disinhibitory symptoms. This is the gap we bridged in our latest study, published in Cerebral Cortex, with coauthors from Spain and Latin America, including GBHI members Sebastián Moguilner and Andrea Slachevsky.

Pulling the brain’s brakes (and failing to do so)

We recruited healthy individuals and two patient groups. Our focus was on persons with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative syndrome characterized by inhibitory deficits. For example, patients may find it hard to stop impulsive actions or inappropriate behavior, such as swearing in public or grabbing someone else’s belongings without permission. As a complementary control group, we evaluated Alzheimer’s disease (AD) patients. In this condition, inhibitory deficits are not primary diagnostic symptoms and they are typically milder than in bvFTD.

We asked participants to read negative and affirmative sentences. Both types could be accompanied by either a yellow or a blue circle. The task required pressing a button when the yellow circle appeared and refraining from pressing it if the blue circle appeared. Crucially, yellow circles appeared much more frequently than blue ones. Thus, participants developed a tendency towards pressing the button, which they had to inhibit every now and then. As they performed the task, we recorded their electrical brain activity and then measured their brain anatomy and connectivity with structural and functional neuroimaging techniques.

In healthy controls, when the task required withholding the response, negative sentences involved distinct changes in the delta band (which supports inhibition). Conversely, bvFTD patients did not exhibit any neurophysiological difference when processing negative and affirmative sentences in inhibitory contexts. Also, in these patients, that disruption was related to brain regions and networks supporting inhibitory skills. These alterations seemed specific to bvFTD, as processing of negative sentences in AD patients elicited the same modulation observed in healthy persons, associated with brain regions that are not crucially involved in inhibition.

Negative words, positive findings

These findings reinforce the idea that comprehension of negative words depends on inhibitory circuits. That is, the same neural mechanisms recruited to suppress a physical action may be engaged when we process negative sentences. Furthermore, our study shows that this link is mediated by different dimensions of the brain, including its electrical activity, structure, and connectivity. No less importantly, this research suggests that negation processing might represent an interesting target for neurological evaluations: tentatively, assessments of this domain could help identify persons with bvFTD and differentiate them from those with other forms of dementia, such as AD.

More generally, this investigation illustrates the potential of interdisciplinary research. The combination of linguistic, neuroscientific, and clinical insights can inspire breakthroughs in the quest to understand how language works, how the brain integrates its surrounding stimuli, and how particular dysfunctions may help differentiate prevalent neurological diseases. All of this, once again, thanks to that ubiquitous, indispensable word: no.

Reference: Díaz-Rivera, M., Birba, A., Fittipaldi, S., Mola, D., Morera, Y., de Vega, M., Moguilner, S., Lillo, P., Slachevsky, A., González Campo, C., Ibáñez, A. & García, A. M. (2022). Multidimensional inhibitory signatures of sentential negation in behavioral variant frontotemporal dementia. Cerebral Cortex, bhac074. doi: