Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation

Highlights

• Non-invasive brain stimulation is increasingly used in neurology and psychiatry.

• The clinical efficacy of these stimulation approaches remains limited.

• Imaging brain networks can help identify where and how to stimulate.

• The treatment of brain disorders will benefit from integrating network science and brain stimulation.

Abstract

The flexible integration of segregated neural processes is essential to healthy brain function. Advances in neuroimaging techniques have revealed that psychiatric and neurological disorders are characterized by anomalies in the dynamic integration of widespread neural populations. Re-establishing optimal neural activity is an important component of the treatment of such disorders. Non-invasive brain stimulation is emerging as a viable tool to selectively restore both local and widespread neural activity in patients affected by psychiatric and neurological disorders. Importantly, the different forms of non-invasive brain stimulation affect neural activity in distinct ways, which has important ramifications for their clinical efficacy. In this review, we discuss how non-invasive brain stimulation techniques influence widespread neural integration across brain regions. We suggest that the efficacy of such techniques in the treatment of psychiatric and neurological conditions is contingent on applying the appropriate stimulation paradigm to restore specific aspects of altered neural integration.

Introduction

Healthy brain function relies on co-ordinated integration of localized activity across widespread neural networks (Catani et al., 2013, Park and Friston, 2013). Understanding how such activity is integrated globally across the brain is arguably one of the greatest challenges facing modern neuroscience (Devor et al., 2013). Although the function and physiological impact of neural activity in specialized brain regions is relatively well understood, we are only beginning to understand how this local activity is integrated between distant regions – for example between primary sensory and higher cognitive areas – or how local damage to, or stimulation of, a specific neural population affects activity elsewhere in the brain.

Our understanding of how local changes in brain activity can influence distant, but functionally related, brain regions has improved in parallel with advances in various forms of brain imaging and brain stimulation methods. For example, stroke patients with local brain lesions often have cognitive impairments that cannot be directly related to the site of damage (Verdon et al., 2010). Further, many of the most common psychiatric and neurological conditions, including depression, obsessive-compulsive disorder and schizophrenia, are associated with impaired integration of functionally related neural networks (Insel, 2010, Menon, 2011, Zhou et al., 2012, Filippi et al., 2013, Fornito et al., 2015).

In recent years it has become clear that various forms of non-invasive brain stimulation (NIBS), such as transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), can modify ongoing brain activity. This has led to a dramatic increase in research applying NIBS in the clinical domain, with the goal of improving abnormal brain function in various conditions (Hummel et al., 2005, Hummel and Cohen, 2006, Passard et al., 2007, Floel, 2014, Liew et al., 2014). The rationale for the use of NIBS has been that if behavioral changes arising from a clinical condition occur due to altered activity within a given brain network, normalizing this activity with NIBS should lead to improved behavior. Such a rationale has motivated studies utilizing NIBS across a range of clinical conditions, including, but not limited to, stroke (Grefkes and Fink, 2014), schizophrenia (Frantseva et al., 2014), depression (Fitzgerald et al., 2009, Fox et al., 2013), and obsessive–compulsive disorder (Fitzgerald et al., 2010). Despite some encouraging results, symptomatic improvement following NIBS in such conditions has generally been modest, and often clinically insignificant (Kalu et al., 2012). Although several reviews have alluded to the effects of NIBS propagating to distant regions via axonal connectivity (Lefaucheur et al., 2014, Liew et al., 2014, Li et al., 2015), they have not considered the consequence of these aspects in the clinical domain. An often overlooked factor affecting the effectiveness of NIBS is the optimal targeting of underlying neural networks associated with the clinical condition (Fox et al., 2012). For instance, the efficacy of TMS in the treatment of depression is influenced by the precise location of stimulation within the DLPFC. The region with the highest efficacy was a region with anticorrelated activity between DLPFC and the subgenual cingulate (Fox et al., 2012). Further, several studies have now investigated how each of the different forms of NIBS alters the activity of large-scale neural networks. Studies suggest that the global effect induced by NIBS is dependent on several factors including electrode placement (Sehm et al., 2013), connectedness of the targeted brain region to other regions (e.g., Rounis et al., 2006 vs. Cocchi et al., 2015), and whether the participant is concurrently undertaking a task (Nitsche et al., 2003, Fregni et al., 2005, Hummel et al., 2005, Antal et al., 2007, Kujirai et al., 2006, Andrews et al., 2011). This interplay between functional interactions between brain regions and NIBS in health and disease has been the focus of many recent studies.

In this review, we discuss prevailing ideas regarding brain function as a complex interaction between multiple neural networks, and outline how different forms of NIBS might interact and modify these networks. We then relate this to how pathological network disturbances could be optimally targeted with specific forms of NIBS. When applying NIBS in the clinical domain, we contend that without a thorough understanding of both the specific network disturbance of the targeted condition, and the mode of action of the NIBS protocol, the desired benefits may not be obtained, or worse, any effects on functioning may be detrimental.