Due to recent advances in machine learning on graphs, representing the connections of the human brain as a network has become one of the most pervasive analytical paradigms. However, most existing graph machine learning-based methods suffer from a subset of five critical limitations: They are (1) designed for simple pair-wise interactions while recent studies on the human brain show the existence of higher-order dependencies of brain regions, (2) designed to perform on pre-constructed networks from time-series data, which limits their generalizability, (3) designed for classifying brain networks, limiting their ability to reveal underlying patterns that might cause the symptoms of a disease or disorder, (4) designed for learning of static patterns, missing the dynamics of human brain activity, and (5) designed in supervised setting, relying their performance on the existence of labeled data. To address these limitations, we present HADiB, an end-to-end anomaly detection model that automatically learns the structure of the hypergraph representation of the brain from neuroimage data. HADiB uses a tetra-stage message-passing mechanism along with an attention mechanism that learns the importance of higher-order dependencies of brain regions. We further present a new adaptive hypergraph pooling to obtain brain-level representation, enabling HADiB to detect the neuroimage of people living with a specific disease or disorder. Our experiments on Parkinson’s Disease, Attention Deficit Hyperactivity Disorder, and Autism Spectrum Disorder show the efficiency and effectiveness of our approaches in detecting anomalous brain activity.