This paper represents the convergence of two distinct journeys. The first began as a friendly bet between PhD colleagues. At the same time, the second was fueled by an ambitious vision to establish a laboratory in Chile dedicated to exploring the causal connections between brain activity and behavior. 

The First Path 

The story begins with a playful bet between PhD students Francisco Zamorano and Pablo Billeke. They hypothesized that in an inhibition task—specifically, the classic go/no-go paradigm—participants would get faster over time in responding to “go” signals as their responses became more automatic. In this task, participants press a button in response to a “go” signal (like a green light) but must refrain from pressing when a sporadic “no-go” (red light) signal appears. To settle the bet, they ran an experiment. To their surprise, participants slowed down their responses to “go” signals as the task progressed.  

Why did this happen? Those unexpected results suggested a more profound underlying process. It seemed that as participants encountered more “go” signals, they anticipated the likelihood of a “no-go” event, thus mentally preparing for the need to inhibit their response. This is akin to crossing a green-lit street but becoming more cautious, expecting the light to change.  

Through a series of studies, those PhD students and later in their early scientific careers found that this dynamic adjustment depended on certain factors. For example, participants only slowed down when “go” stimuli appeared faster (1). Additionally, they observed that while children show a similar anticipatory adjustment, this response is absent in individuals with attention difficulties, such as those with ADHD (2). 

The second Path 

 Years later, two new students, María Paz Martínez and Gabriela Valdebenito, sought to establish a laboratory to measure brain activity and apply stimulation techniques to study brain-behavior causality. After securing grants and setting up the lab, they began integrating behavioral models with brain activity to explore these causal relationships. 

 With the support of Antoni Valero, they implemented transcranial magnetic stimulation (TMS), and under Rafael Polania’s guidance, they identified latent variables in complex behaviors through cognitive-computational modeling. An early study revealed a region in the parietal cortex associated with perceived uncertainty during decision-making. Using TMS to disrupt parietal activity, they demonstrated that this brain region plays a causal role in processing uncertainty (3). 

The Current Paths Converge 

In this study, computational models revealed that participants’ responses in the go/no-go task were influenced by both the probability of the “no-go” signal appearing and the timing of “go” signals in a nonlinear manner. This behavior aligned with a learning model, suggesting that as participants encountered more frequent “go” signals, they recalibrated, heightening their awareness of the occasional but crucial “no-go” moments. This adaptive process illustrates a sophisticated interplay between anticipation and inhibition, shedding light on how the brain manages uncertainty in real time. 

Key Findings 

Our collaborative research combined behavioral tasks and neural techniques, revealing that: 

1. Multiple factors influence expectation dynamics in response to stimuli requiring inhibition and demand continuous adaptation to environmental changes. 
2. Metabolic and electrophysiological markers (measured via fMRI and theta-range EEG) in a network, including the prefrontal cortex’s superior gyrus, are linked to these adaptive expectations. 
3. Non-invasive brain stimulation can enhance theta oscillations in this region, modulating behavior and improving anticipatory precision in complex stimulus contexts. 

These insights, born from the intersection of two investigative paths, offer a window into the mechanisms underlying attention-related disorders, suggesting new possibilities for therapeutic approaches that target brain function. 

References:

1. Zamorano, F. et al. Temporal Constraints of Behavioral Inhibition: Relevance of Inter-stimulus Interval in a Go-Nogo Task. Plos One 9, e87232 (2014).
2. Zamorano, F. et al. Lateral Prefrontal Theta Oscillations Reflect Proactive Cognitive Control Impairment in Males With Attention Deficit Hyperactivity Disorder. Front. Syst. Neurosci. 14, 37 (2020).
3. Valdebenito-Oyarzo, G. et al. The parietal cortex has a causal role in ambiguity computations in humans. PLOS Biol. 22, e3002452 (2024).