A non-invasive, multimodal approach to restore functional networks and cognition in alzheimer's disease and frontotemporal dementia.

Background and Significance

The disruption of specific large-scale networks is a key feature of several neurodegenerative disorders. Alzheimer`s disease (AD) is associated with the progressive degeneration of the so-called default mode network (DMN), while behaviouralfrontotemporal dementia (bvFTD) is associated with degeneration of the `salience` network (SN)(Pievani et al, Lancet Neurol 2011). Network disruption tracks the pathology and drives the clinical symptoms, hence targeting largescalenetworks might offer a novel and effective approach to restore cognition in these conditions.

Non invasive brain stimulation techniques (e.g., repetitive transcranial direct current stimulation-tDCS, or transcranialmagnetic stimulation) have shown promising in modulating cognition in healthy and patients by stimulating task-specificnetworks or, alternatively, by suppressing anti-correlated regions (Cotelli et al, JNNP 2011; Eldaief et al, PNAS 2011).

Largely unknown is whether stimulating the DMN and SN in AD and bvFTD can improve cognition.Aim of this study is to combine resting-state fMRI (rs-fMRI) networks mapping with tDCS to modulate the DMN and SN inAD and bvFTD. Since the DMN and SN are mutually anti-correlated (DMN connectivity is reduced and SN connectivity isenhanced in AD, while the opposite is seen in bvFTD; Zhou et al, Brain 2010), we will test whether the stimulation of disease-specific networks or, alternatively, the suppression of anti-correlated networks can modulate cognition.

Specific aims

1. To assess the cognitive effect of disease-specific networks stimulation in AD (DMN stimulation) and bvFTD (SNstimulation);
2. To assess the cognitive effect of anti-correlated networks suppression in AD (SN suppression) and bvFTD (DMN suppression);
3. To investigate correlations between tDCS-related network changes and biomarker changes in AD and bvFTD.

Impact and Implications

The stimulation of disease-specific networks might prove a novel, effective, and non-pharmacological alternative to drug treatment in AD and bvFTD patients. The possibility to modulate brain function by suppressing anti-correlated networksmight open the venue to minimally-invasive therapeutic approaches.