Neuromodulation of disrupted brain networks

Neuromodulation technologies have experienced an incredible development in the past twenty years. Scientists and clinicians have access to a toolbox of invasive (e.g., neural implants, deep brain stimulation) and noninvasive (e.g., transcranial brain stimulation) techniques that allow us to stimulate and modulate human brain activity with measurable impact on human perception, cognition, and emotion. Noninvasive brain stimulation (NIBS) applies either low output electric current, magnetic pulses, or sound waves, transcranially through the intact skull, to either increase or decrease neural activity levels, or to modulate the connectivity between different areas of the brain within functional networks controlling human cognition. Transcranial magnetic stimulation (TMS) is the most versatile and best-established NIBS technology with protocols capable of also modulating brain activity beyond the duration of the stimulation itself, thereby inducing longer lasting neuroplastic changes. TMS is therefore used in many labs worldwide as a basic brain research tool to study how the healthy human brain works. TMS is also a recognized, evidence-based, and regulatory approved therapy for treating various brain disorders such as depression, neuropathic pain, or stroke. In recent years, TMS has been combined with functional magnetic resonance imaging (fMRI) to combine the complementary assets of both approaches, that is, a noninvasive method to increase or inhibit ongoing local neural activity (TMS) with a noninvasive method to assess the direct and indirect activity changes induced by TMS throughout the entire human brain. This article describes the various ways in which fMRI can be integrated with TMS. FMRI before TMS allows to identify personalized stimulation targets and biomarkers for clinical responses. Simultaneous TMS and fMRI revealed that TMS, unlike previously assumed, can also reach subcortical brain regions via functional network connectivity to the directly stimulated cortical target, and that those cortico-subcortical network effects of TMS are state-dependent, thus interacting with the participants’ momentary neural/cognitive state. These insights are now used to optimize brain stimulation treatments for a variety of neuropsychiatric disorders.