Much of neuroscience research is motivated by diseases. Some major research questions pertain to vulnerability: what brain areas or systems are vulnerable to perturbations that trigger dysfunction? And which individuals are vulnerable to developing a disease? The articles in this issue touch upon these questions.

Hippocampal dysfunction is central to many disorders, as well as to age-related cognitive impairment. On page 585, Small and colleagues show that specific hippocampal subregions are differentially affected in different conditions, and argue that this differential vulnerability helps to explain the diversity of symptoms in various hippocampus-linked conditions.

A major goal of biomarker research is to identify factors that determine disease vulnerability. In a Perspective on page 603, Walsh and colleagues discuss the substantial scientific challenges and social and ethical concerns associated with the development and application of autism biomarkers. Notably, many of these concerns arise from the question of whether autism should be viewed as a disability or as a cognitive difference.

Migraine is a complex and disabling brain disorder, and an important question is what drives the activation of pain pathways in vulnerable individuals. On page 570, Goadsby and colleagues review the evidence that regions of the brainstem and forebrain are involved in modulating migraine pain and that dysfunction in these areas may contribute to the pathophysiology of this disorder.

Finally, on page 553, Christopher Colwell describes the mechanisms that link the circadian rhythms in gene transcription and neural activity in the suprachiasmatic nucleus. He proposes that these neural activity rhythms may be the vulnerable component of the circadian system, as they are the first to decline with ageing and in neurodegenerative disease models.