Vehicle accidents are the primary cause of fatalities worldwide. Most often, experiencing fatigue on the road leads to operator errors and behavioral lapses. Thus, there is a need to predict the cognitive state of drivers, particularly their fatigue level. Electroencephalography (EEG) has been demonstrated to be effective for monitoring changes in the human brain state and behavior. Thirty-seven subjects participated in this driving experiment and performed a perform lane-keeping task in a visual-reality environment. Three domains, namely, frequency, temporal and 2D spatial information, of EEG channel location were comprehensively considered. A 4D convolutional neural network (4D CNN) algorithm was then proposed to associate all information from the EEG signals and the changes in the human state and behavioral performance. 4D CNN achieves superior forecasting performance over 2D CNN, 3D CNN and shallow networks. The results showed a 3.82% improvement in the RMSE, a 3.45% improvement in the error rate, and a 11.98% improvement in the correlation coefficient with 4D CNN compared with 3D CNN. The 4D CNN algorithm extracts the significant theta and alpha activations in the frontal and posterior cingulate cortices under distinct fatigue levels. This work contributes to enhancing our understanding of deep learning methods in the analysis of EEG signals. We even envision that deep learning might serve as a bridge between translation neuroscience and further real-world applications.