Humans consistently make suboptimal decisions involving random events, yet the underlying neural mechanisms remain elusive. Using functional MRI and a matching pennies game that captured subjects' increasing tendency to predict the break of a streak as it continued [i.e., the "gambler's fallacy" (GF)], we found that a strong blood oxygen level-dependent response in the left lateral prefrontal cortex (LPFC) to the current outcome preceded the use of the GF strategy 10 s later. Furthermore, anodal transcranial direct current stimulation over the left LPFC, which enhances neuronal firing rates and cerebral excitability, increased the use of the GF strategy, and made the decisions more "sticky." These results reveal a causal role of the LPFC in implementing suboptimal decision strategy guided by false world models, especially when such strategy requires great resources for cognitive control.decision-making | brain stimulation | random process T he ability to perceive patterns and to use them to guide decisions is an important aspect of human cognition. During the long history of evolution, the human brain has been well adapted to the statistical regularities in the environment (1, 2). Nevertheless, humans have been consistently shown to be bad at making decisions involving "independently and identically distributed" random events generated by the Bernoulli process, exhibiting suboptimal behaviors such as probability matching and the "gambler's fallacy" (GF) (3-5). In particular, the GF is an increasing tendency to predict the break of a streak generated by a random process (e.g., flipping a fair coin) when the streak gets longer (6), and has been observed in many laboratory and reallife situations (6-9).Behavioral research has suggested that the GF is a cognitive bias generated by a false perception of the random process (e.g., the small number law) (6, 10), which is probably formed through years of evolution in response to the pattern-rich world (1, 2). Consistently, the subjective beliefs about the specific generating mechanisms (i.e., the world model) could significantly affect participants' predictions (6-9). Computational models show that a rational mind guided by a false "world model" (i.e., outcome dependency) could well generate this type of suboptimal decisions, which can be changed by alternations of the world model (11). Nevertheless, the neural mechanisms of the GF have not been clearly addressed.Several lines of research have suggested the involvement of the prefrontal cortex (PFC) in several decision processes that could contribute to the GF strategy. First, the PFC is good at detecting and constructing patterns, especially out of randomness (12). Second, the PFC plays an important role in decision making by encoding a particular state of the environment and the desirability of the outcome expected from such a state (13,14). During the pennies-matching gamble, PFC neurons have been shown to encode multiple types of information related to decision making (including animals' past decisions, payoffs, and ...