Device-based non-invasive brain stimulation (NIBS) techniques show promise for the treatment of neurological and psychiatric disorders, although inconsistencies in protocol designs and study findings can make the field difficult to navigate. In this Review, we discuss applications of NIBS for enhancing cognitive and motor function in people with various neurological diseases that are characterized by disruption of large-scale brain networks, including neurodegenerative diseases and brain lesion disorders such as stroke and traumatic brain injury. In particular, we focus on repetitive transcranial magnetic stimulation and transcranial electrical stimulation, as these techniques have been widely used in clinical settings and randomized controlled trials. We summarize and synthesize current knowledge, and highlight gaps and shortcomings in the existing research that make it difficult to draw firm conclusions, including small sample sizes, heterogeneous patient populations and variations in stimulation protocols. We believe that a rapid evolution of NIBS techniques from state-dependent, network-informed, multifocal and subcortical paradigms to individualized electric field modelling and accelerated NIBS protocols will improve the management of neurological disorders. However, realizing this potential will require us to address crucial challenges and acquire deeper mechanistic insights, with the aim of developing adaptive, biomarker-driven protocols to optimize target engagement, dosing and timing for each patient.

• Publication type
• Journal Article MeSH
• Review MeSH

Transcranial direct current stimulation combined with cognitive training (tDCS-cog) represents a promising approach to combat cognitive decline among healthy older adults and patients with mild cognitive impairment (MCI). In this 5-day-long double-blinded randomized trial, we investigated the impact of intensified tDCS-cog protocol involving two trains of stimulation per day on working memory (WM) enhancement in 35 amnestic and multidomain amnestic MCI patients. Specifically, we focused to improve WM tasks relying on top-down attentional control and hypothesized that intensified tDCS would enhance performance of visual object matching task (VOMT) immediately after the stimulation regimen and at a 1-month follow-up. Secondarily, we explored whether the stimulation would augment online visual working memory training. Using fMRI, we aimed to elucidate the neural mechanisms underlying the intervention effects by analyzing BOLD activations during VOMT. Our main finding revealed no superior after-effects of tDCS-cog over the sham on VOMT among individuals with MCI as indicated by insignificant immediate and long-lasting after-effects. Additionally, the tDCS-cog did not enhance online training as predicted. The fMRI analysis revealed brain activity alterations in right insula that may be linked to tDCS-cog intervention. In the study we discuss the insignificant behavioral results in the context of the current evidence in tDCS parameter space and opening the discussion of possible interference between trained cognitive tasks.

• MeSH
• Dorsolateral Prefrontal Cortex MeSH
• Double-Blind Method MeSH
• Cognitive Dysfunction * therapy   MeSH
• Memory, Short-Term physiology   MeSH
• Humans MeSH
• Brain diagnostic imaging   MeSH
• Prefrontal Cortex physiology   MeSH
• Transcranial Direct Current Stimulation * methods   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

The vertex has been used as a suitable control stimulation site in repetitive transcranial magnetic stimulation studies. The objectives of this study are (1) to assess cognitive performance (CP) after theta burst stimulation (TBS); (2) to evaluate whether clinically relevant cortical areas might be reached by vertex stimulation and how that might influence CP. Twenty young healthy subjects performed a cognitive task prior to and immediately after intermittent TBS (iTBS) and continuous TBS (cTBS) of two active cortical stimulation sites and the vertex. We used the Wilcoxon signed-rank test to compare the pre- and post-stimulation reaction times (RTs) and a mixed ANOVA analysis to evaluate the effect of the stimulation on changes in RTs. A three-dimensional finite-element model (FEM) was used to calculate the vertex TBS-induced electrical field (E-field) in the adjacent regions of interest (ROIs). Correlation analyses were performed between E-fields in the ROIs and cognitive outcomes. We found a significant effect only of the stimulation time factor (F (1,12) = 65.37, p < 0.001) on RT shortening, with no superiority of the active site stimulation compared to the vertex stimulation. In 73.5% of vertex TBS sessions, a significant E-field was induced in at least one ROI. We found a negative association between the magnitude of the iTBS-induced E-fields and RT changes (R = - 0.54, p = 0.04). TBS protocols may lead to changes in CP when applied over the craniometrically targeted vertex. We therefore suggest not using a conventional approach as a vertex targeting method.

• Keywords
• Cognitive, Control condition, SimNIBS, Transcranial magnetic stimulation, Vertex stimulation, rTMS,
• MeSH
• Head * MeSH
• Humans MeSH
• Reaction Time MeSH
• Theta Rhythm MeSH
• Transcranial Magnetic Stimulation * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

INTRODUCTION: Impaired copy of intersecting pentagons from the Mini-Mental State Examination (MMSE), has been used to assess dementia in Parkinson's disease (PD). We used a digitizing tablet during the pentagon copying test (PCT) as a potential tool for evaluating early cognitive deficits in PD without major cognitive impairment. We also aimed to uncover the neural correlates of the identified parameters using whole-brain magnetic resonance imaging (MRI). METHODS: We enrolled 27 patients with PD without major cognitive impairment and 25 age-matched healthy controls (HC). We focused on drawing parameters using a digitizing tablet. Parameters with between-group differences were correlated with cognitive outcomes and were used as covariates in the whole-brain voxel-wise analysis using voxel-based morphometry; familywise error (FWE) threshold p < 0.001. RESULTS: PD patients differed from HC in attention domain z-scores (p < 0.0001). In terms of tablet parameters, the groups differed in Shannon entropy (horizontal in-air, p = 0.003), which quantifies the movements between two strokes. In PD, a correlation was found between the median of Shannon entropy (horizontal in-air) and attention z-scores (R = -0.55, p = 0.006). The VBM revealed an association between our drawing parameter of interest and gray matter (GM) volume variability in the right superior parietal lobe (SPL). CONCLUSION: Using a digitizing tablet during the PCT, we identified a novel entropy-based parameter that differed between the nondemented PD and HC groups. This in-air parameter correlated with the level of attention and was linked to GM volume variability of the region engaged in spatial attention.

• Keywords
• In-air movement, Kinematic analysis, Parkinson's disease, Pentagon copying test, Shannon entropy,
• MeSH
• Entropy MeSH
• Cognitive Dysfunction * MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Neuropsychological Tests MeSH
• Parkinson Disease * complications   diagnostic imaging   psychology   MeSH
• Gray Matter MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.

• MeSH
• Frontal Lobe diagnostic imaging   physiopathology   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Cross-Over Studies MeSH
• Memory, Short-Term physiology   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Adolescent MeSH
• Young Adult MeSH
• Neuropsychological Tests MeSH
• Transcranial Direct Current Stimulation MeSH
• Reaction Time physiology   MeSH
• Parietal Lobe diagnostic imaging   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Enhancing cognitive functions through noninvasive brain stimulation is of enormous public interest, particularly for the aging population in whom processes such as working memory are known to decline. In a randomized double-blind crossover study, we investigated the acute behavioral and neural aftereffects of bifrontal and frontoparietal transcranial direct current stimulation (tDCS) combined with visual working memory (VWM) training on 25 highly educated older adults. Resting-state functional connectivity (rs-FC) analysis was performed prior to and after each stimulation session with a focus on the frontoparietal control network (FPCN). The bifrontal montage with anode over the left dorsolateral prefrontal cortex enhanced VWM accuracy as compared to the sham stimulation. With the rs-FC within the FPCN, we observed significant stimulation × time interaction using bifrontal tDCS. We found no cognitive aftereffects of the frontoparietal tDCS compared to sham stimulation. Our study shows that a single bifrontal tDCS combined with cognitive training may enhance VWM performance and rs-FC within the relevant brain network even in highly educated older adults.

• MeSH
• Frontal Lobe MeSH
• Double-Blind Method MeSH
• Cross-Over Studies MeSH
• Cognition * MeSH
• Cognitive Behavioral Therapy methods   MeSH
• Memory, Short-Term MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Neuropsychological Tests MeSH
• Prefrontal Cortex MeSH
• Transcranial Direct Current Stimulation methods   MeSH
• Psychomotor Performance MeSH
• Aged MeSH
• Educational Status MeSH
• Parietal Lobe MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: Cognitive impairment in Parkinson's disease (PD) is associated with altered connectivity of the resting state networks (RSNs). Longitudinal studies in well cognitively characterized PD subgroups are missing. OBJECTIVES: To assess changes of the whole-brain connectivity and between-network connectivity (BNC) of large-scale functional networks related to cognition in well characterized PD patients using a longitudinal study design and various analytical methods. METHODS: We explored the whole-brain connectivity and BNC of the frontoparietal control network (FPCN) and the default mode, dorsal attention, and visual networks in PD with normal cognition (PD-NC, n = 17) and mild cognitive impairment (PD-MCI, n = 22) as compared to 51 healthy controls (HC). We applied regions of interest-based, partial least squares, and graph theory based network analyses. The differences among groups were analyzed at baseline and at the one-year follow-up visit (37 HC, 23 PD all). RESULTS: The BNC of the FPCN and other RSNs was reduced, and the whole-brain analysis revealed increased characteristic path length and decreased average node strength, clustering coefficient, and global efficiency in PD-NC compared to HC. Values of all measures in PD-MCI were between that of HC and PD-NC. After one year, the BNC was further increased in the PD-all group; no changes were detected in HC. No cognitive domain z-scores deteriorated in either group. CONCLUSION: As compared to HC, PD-NC patients display a less efficient transfer of information globally and reduced BNC of the visual and frontoparietal control network. The BNC increases with time and MCI status, reflecting compensatory efforts.

• Keywords
• Between-network connectivity, Parkinson’s disease, cognitive resting state brain networks, functional MRI, graph measures, longitudinal, mild cognitive impairment, partial least squares analysis,
• MeSH
• Adult MeSH
• Cognitive Dysfunction etiology   pathology   psychology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Magnetic Resonance Imaging MeSH
• Brain diagnostic imaging   pathology   MeSH
• Nerve Net diagnostic imaging   pathology   MeSH
• Neuroimaging MeSH
• Parkinson Disease complications   pathology   psychology   MeSH
• Prefrontal Cortex pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Parietal Lobe pathology   MeSH
• Mental Status and Dementia Tests MeSH
• Visual Cortex pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH