Cognitive enhancement with Salience Network electrical stimulation is influenced by network structural connectivity

The Salience Network (SN) and its interactions are important for cognitive control. We have previously shown that structural damage to the SN is associated with abnormal functional connectivity between the SN and Default Mode Network (DMN), abnormal DMN deactivation, and impaired response inhibition, which is an important aspect of cognitive control. This suggests that stimulating the SN might enhance cognitive control. Here, we tested whether non-invasive transcranial direct current stimulation (TDCS) could be used to modulate activity within the SN and enhance cognitive control. TDCS was applied to the right inferior frontal gyrus/anterior insula cortex during performance of the Stop Signal Task (SST) and concurrent functional (f)MRI. Anodal TDCS improved response inhibition. Furthermore, stratification of participants based on SN structural connectivity showed that it was an important influence on both behavioural and physiological responses to anodal TDCS. Participants with high fractional anisotropy within the SN showed improved SST performance and increased activation of the SN with anodal TDCS, whilst those with low fractional anisotropy within the SN did not. Cathodal stimulation of the SN produced activation of the right caudate, an effect which was not modulated by SN structural connectivity. Our results show that stimulation targeted to the SN can improve response inhibition, supporting the causal influence of this network on cognitive control and confirming it as a target to produce cognitive enhancement. Our results also highlight the importance of structural connectivity as a modulator of network to TDCS, which should guide the design and interpretation of future stimulation studies

Expanding Your Cognitive Capacity: An Assessment of the Neuroplastic Changes Associated with Mindfulness Training and Transcranial Stimulation

Given that mindfulness-based training techniques (MBT) stimulates and pushes ones core cognitive control capacity limits, brain stimulation techniques, such as transcranial direct current stimulation (tDCS), can be used to facilitate the ongoing neural patterns of functional connectivity toward long-lasting neuroplastic change. The current study assessed the combined effects of MBT with right frontal tDCS on cognitive control abilities and their corresponding brain patterns of activation using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). This study found an enhancement in working memory and sustained attention performance along with changes in the attention-related P3 component and its theta and alpha oscillatory profiles recorded by EEG. Furthermore, a reconfiguration in the chronnectome of large-scale resting-state networks was observed using resting-state fMRI, in addition to task-related changes in the polymodal neural architecture associated with encoding and adaptation, which may bridge the necessary connections from near to far transfer gains

Neural processes underpinning pain perception : genetic, temporal, and behavioral factors

Pain is an alarm system – warning us of dangers in the environment – yet becomes problematic when it transitions into chronic pain. It is defined, according to the International Association of Pain as “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”. In advancing our knowledge of the underlying mechanisms of acute pain, it is relevant to understand sources of variability in pain perception. One such source is the genetic influence on brain function. This can be studied using a classic twin design to infer the proportion of variance in brain activation attributed to genetics. Another source of variation pertains to the temporal fluctuations in brain activity that could track pain processing. This was studied here using time-varying functional connectivity. Furthermore, since pain arises through large-scale interactions in the brain – the purpose here is to study pain and related processes through network neuroscience. Specifically, how functionally specialized – or segregated – neural structures of the brain integrate to shape pain

Examining targeted brain stimulation to improve vigilant attention in right-hemispheric stroke

Neglect is a disabling neuropsychological syndrome frequently observed following right-hemispheric stroke. Affected individuals present with attentional deficits, ranging from a difficulty in orienting towards the contralesional space to a generalised difficulty with maintaining attention over time. Neglect may be persistent - particularly its non-lateralised component. This thesis focused on investigating the efficacy of a potential treatment involving non-invasive targeted brain stimulation to improve vigilant attention. In a randomised double-blind sham-controlled crossover study, healthy individuals across the lifespan and stroke patients with attentional impairments received real and sham transcranial direct current stimulation (tDCS) whilst performing a vigilance task. A high-definition montage was used to constrain current delivery over the right dorsolateral prefrontal cortex, a key region of the vigilance network. Results show that, at the group level, targeted tDCS improved target detection across all groups. By examining performance across temporal epochs, it was noted that tDCS did not impede worsening of performance with increasing time-on-task. The superiority of tDCS was however found throughout the task, outlasting stimulation delivery. A lesion anatomy study indicated that task performance was related to lesion location rather than volume. In addition, variability in patients' response to treatment was observed and linked to lesion profile, revealing that damage to specific brain regions caused lack of tDCS response. Finally, a concurrent tDCS-fMRI study was conducted to examine brain network response to tDCS. Brain stimulation did not affect local connectivity, but rather influenced functional connectivity within large-scale networks in the contralateral hemisphere. This finding emerged across groups using different analysis approaches, confirming its robustness. This systematic behavioural and imaging investigation supports a role of tDCS to improve non-lateralised deficits of neglect, which could be harnessed in future clinical trials. Furthermore, it sheds light on network response to precise cortical targeting, revealing its widespread effect.Open Acces

Precision non-implantable neuromodulation therapies : a perspective for the depressed brain

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although nonimplantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more ‘‘precision-oriented’’ practice

Abnormal dorsal attention network activation in memory impairment after traumatic brain injury

Memory impairment is a common, disabling effect of traumatic brain injury. In healthy individuals, successful memory encoding is associated with activation of the dorsal attention network as well as suppression of the default mode network. Here, in traumatic brain injurypatients we examined whether: i) impairments in memory encoding are associated with abnormal brain activation in these networks; ii) whether changes in this brain activity predict subsequent memory retrieval; and iii) whether abnormal white matter integrity underpinningfunctional networks is associated with impaired subsequent memory. 35 patients with moderate-severetraumatic brain injury aged 23-65 years (74% males) in the post-acute/chronic phase after injury and 16 healthy controls underwent functional MRI during performance of an abstract image memory encoding task. Diffusion tensor imaging was used to assess structural abnormalities across patient groups compared to 28 age-matched healthy controls. Successful memory encoding across all participants was associated with activation of the dorsal attention network, the ventral visual stream and medial temporal lobes. Decreased activation was seen in the default mode network. Patients with preserved episodic memory demonstrated increased activation in areas of the dorsal attention network.Patients with impaired memory showed increased left anterior prefrontal activity. White matter microstructure underpinning connectivity between core nodes of the encoding networks was significantly reduced in patients with memory impairment. Our results show for the first time that patients with impaired episodic memory show abnormal activation of key nodes within the dorsal attention network and regions regulating default mode network activity during encoding. Successful encoding was associated with an opposite direction of signal change between patients with and without memory impairment, suggesting that memory encoding mechanisms could be fundamentally altered in this population. We demonstrate a clear relationship between functional networks activated during encoding and underlying abnormalities within the structural connectome in patients with memory impairment. We suggest that encoding failures in this group are likely due to failed control of goal-directed attentional resources

Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation

Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation

Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at “rest.” A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large‐scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within‐DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large‐scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies