Effects of anodal tDCS on electroencephalography correlates of cognitive control in mild-to-moderate traumatic brain injury.

BACKGROUND: Transcranial direct current stimulation (tDCS) may provide a potential therapy for cognitive deficits caused by traumatic brain injury (TBI), yet its efficacy and mechanisms of action are still uncertain. OBJECTIVE: We hypothesized that anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) would boost the influence of a cognitive training regimen in a mild-to-moderate TBI (mmTBI) sample. Cognitive enhancement was measured by examining event-related potentials (ERPs) during cognitive control tasks from pre- to post-treatment. METHODS: Thirty-four participants with mmTBI underwent ten sessions of cognitive training with active (n = 17) or sham (n = 17) anodal tDCS to the left DLPFC. ERPs were assessed during performance of an auditory oddball (3AOB), N-back, and dot pattern expectancy (DPX) task before and after treatment. RESULTS: P3b amplitudes significantly decreased from baseline to post-treatment testing, regardless of tDCS condition, in the N-back task. The active tDCS group demonstrated a significantly increased P3a amplitude in the DPX task. No statistically significant stimulation effects were seen during the 3AOB and N-back tasks. CONCLUSION: Active anodal tDCS paired with cognitive training led to increases in P3a amplitudes in the DPX, inferring increased cognitive control. P3b decreased in the N-back task demonstrating the effects of cognitive training. These dissociated P3 findings suggest separate mechanisms invoked by different neuroplasticity-inducing paradigms (stimulation versus training) in brain networks that support executive functioning.

Ventromedial Prefrontal-Anterior Cingulate Hyperconnectivity and Resilience to Apathy in Traumatic Brain Injury.

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining in which patients apathy does or does not develop post-TBI. We aimed to elucidate the impact of TBI on motivational neural circuits and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging data were collected in patients with subacute mild TBI (n = 44), chronic mild-to-moderate TBI (n = 26), and nonbrain-injured control participants (CTRL; n = 28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori vmPFC seed adopted from a motivated decision-making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. The vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating previous work suggesting that apathy has an enduring impact in TBI. The vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Last, we subdivided the TBI group based on patients above versus below the threshold for "clinically significant apathy," finding that TBI patients with clinically significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represent an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.

Cerebral Perfusion Effects of Cognitive Training and Transcranial Direct Current Stimulation in Mild-Moderate TBI.

Background: Persistent post-traumatic symptoms (PPS) after traumatic brain injury (TBI) can lead to significant chronic functional impairment. Pseudocontinuous arterial spin labeling (pCASL) has been used in multiple studies to explore changes in cerebral blood flow (CBF) that may result in acute and chronic TBI, and is a promising neuroimaging modality for assessing response to therapies. Methods: Twenty-four subjects with chronic mild-moderate TBI (mmTBI) were enrolled in a pilot study of 10 days of computerized executive function training combined with active or sham anodal transcranial direct current stimulation (tDCS) for treatment of cognitive PPS. Behavioral surveys, neuropsychological testing, and magnetic resonance imaging (MRI) with pCASL sequences to assess global and regional CBF were obtained before and after the training protocol. Results: Robust improvements in depression, anxiety, complex attention, and executive function were seen in both active and sham groups between the baseline and post-treatment visits. Global CBF decreased over time, with differences in regional CBF noted in the right inferior frontal gyrus (IFG). Active stimulation was associated with static or increased CBF in the right IFG, whereas sham was associated with reduced CBF. Neuropsychological performance and behavioral symptoms were not associated with changes in CBF. Discussion: The current study suggests a complex picture between mmTBI, cerebral perfusion, and recovery. Changes in CBF may result from physiologic effect of the intervention, compensatory neural mechanisms, or confounding factors. Limitations include a small sample size and heterogenous injury sample, but these findings suggest promising directions for future studies of cognitive training paradigms in mmTBI.

Joint analysis of frontal theta synchrony and white matter following mild traumatic brain injury.

Some of the most disabling aspects of mild traumatic brain injury (mTBI) include lingering deficits in executive functioning. It is known that mTBI can damage white matter tracts, but it remains unknown how this structural brain damage translates into cognitive deficits. This experiment utilized theta band phase synchrony to identify the dysfunctional neural operations that contribute to cognitive problems following mTBI. Sub-acute stage (< 2 weeks) mTBI patients (N = 52) and healthy matched controls (N = 32) completed a control-demanding task with concurrent EEG. Structural MRI was also collected. While there were no performance-specific behavioral differences between groups in the dot probe expectancy task, the degree of theta band phase synchrony immediately following injury predicted the degree of symptom recovery two months later. Although there were no differences in fractional anisotropy (FA) between groups, joint independent components analysis revealed that a smaller network of lower FA-valued voxels contributed to a diminished frontal theta phase synchrony network in the mTBI group. This finding suggests that frontal theta band markers of cognitive control are sensitive to sub-threshold structural aberrations following mTBI.

Executive function predictors of delayed memory deficits after mild traumatic brain injury.

Delayed memory deficits are common for patients with mild traumatic brain injury (mTBI), according to a recent systematic review of meta-analyses (Karr et al., 2014). However, there has been little work to identify different cognitive processes that may be underpinning these delayed memory deficits for mTBI. Frontal cortex is important for delayed memory, and is implicated in the pathophysiology of mTBI; moreover, frontal lobes are typically considered the locus of executive abilities. To further explore these relationships, we sought to partly explain delayed memory deficits after mTBI by examining behavioral indicators of executive function. Results showed that sub-acute as well as chronic mTBI patients performed worse than controls on the delayed memory trial of the Hopkins Verbal Learning Test-Revised (Brandt & Benedict, 2001), recalling approximately 18% and 15% fewer words, respectively. Furthermore, worse delayed memory performance was associated with less use of the cognitive strategy of semantic clustering, and with lower scores for the executive function composite from a standardized neuropsychological battery (NIH EXAMINER; Kramer et al., 2014). In contrast, serial clustering, a memory organizational strategy thought to be less dependent on executive function, did not show strong relationships to clinical status or delayed memory performance. This exploratory work suggests novel hypotheses to be tested in future, confirmatory studies, including that general executive functions and/or semantic clustering will mediate delayed memory deficits following mTBI.

ERPs predict symptomatic distress and recovery in sub-acute mild traumatic brain injury.

Mild traumatic brain injury (mTBI) can affect high-level executive functioning long after somatic symptoms resolve. We tested if simple EEG responses within an oddball paradigm could capture variance relevant to this clinical problem. The P3a and P3b components reflect bottom-up and top-down processes driving engagement with exogenous stimuli. Since these features are related to primitive decision abilities, abnormal amplitudes following mTBI may account for problems in the ability to exert executive control. Sub-acute (<2 weeks) mTBI participants (N = 38) and healthy controls (N = 24) were assessed at an initial session as well as a two-month follow-up (sessions 1 and 2). We contrasted the initial assessment to a comparison group of participants with chronic symptomatology following brain injury (N = 23). There were no group differences in P3a or P3b amplitudes. Yet in the sub-acute mTBI group, higher symptomatology on the Frontal Systems Behavior scale (FrSBe), a questionnaire validated as measuring symptomatic distress related to frontal lobe injury, correlated with lower P3a in session 1. This relationship was replicated in session 2. These findings were distinct from chronic TBI participants, who instead expressed a relationship between increased FrSBe symptoms and a lower P3b component. In the sub-acute group, P3b amplitudes in the first session correlated with the degree of symptom change between sessions 1 and 2, above and beyond demographic predictors. Controls did not show any relationship between FrSBe symptoms and P3a or P3b. These findings identify symptom-specific alterations in neural systems that vary along the time course of post-concussive symptomatology.

Transcranial direct current stimulation (tDCS) over right temporoparietal junction (rTPJ) for social cognition and social skills in adults with autism spectrum disorder (ASD).

Social deficits are core to autism spectrum disorder (ASD). Current treatments are extremely time- and labor-intensive. Transcranial direct current stimulation (tDCS) may be a promising treatment modality to safely enhance treatments targeting social cognition and social skills. This pilot study investigates the effectiveness of social skills treatment interventions paired with anodal tDCS for six adults 18-58 years with ASD. Differences were predicted on the verbal fluency (VF) test and a test of social skills (TASSK-M) for verum (2.0 mA) vs. sham tDCS, which was randomly assigned in a within-subjects, double-blinded design in adults with ASD with normal or higher cognitive functioning. The anode electrode was placed over right temporoparietal (CP6) and cathode over ipsilateral deltoid. Wilcoxon signed-rank tests for paired data indicated that participants received a significantly higher score on the VF test after receiving verum tDCS compared to sham tDCS, with no significant differences found on the TASSK-M. Post-hoc analysis showed that the emotion-word portion of the VF test, specifically, indicated significant differences when comparing verum to sham tDCS conditions. These findings provide optimism for the use of tDCS as delivered in the current study paired with social skills treatment interventions for ASD, particularly for improving skills of emotion verbal fluency.

Transcranial Direct Current Stimulation to the Right Temporoparietal Junction for Social Functioning in Autism Spectrum Disorder: A Case Report.

OBJECTIVES: While there is evidence of improved social functioning after applying transcranial direct current stimulation (tDCS) at the right temporoparietal junction (rTPJ) in individuals who are healthy, no current studies have investigated the use of tDCS at the rTPJ to improve social functioning in individuals with autism spectrum disorder (ASD). This case investigates the use of tDCS applied to the rTPJ to target social functioning in a high-functioning adult with ASD. METHODS: The authors present a case of an 18-year old patient with ASD treated successfully with tDCS; 1.5 mA of tDCS was applied once a day for 30 minutes for 8 consecutive days with the anode electrode over rTPJ (CP6 in the 10/10 electroencephalogram system) and the cathode electrode placed on the ipsilateral deltoid. Behavioral outcome was assessed using the Autism Treatment Evaluation Checklist prior to tDCS, after the final tDCS session, and at 2 months after tDCS. An additional, informal follow-up was also made 1 year after tDCS. RESULTS: Autism Treatment Evaluation Checklist showed substantial improvement in social functioning from baseline to post-tDCS, which was maintained at 2 months. The patient also reported lessened feelings of anger and frustration over social disappointments. Informal follow-up 1 year after stimulation indicates that the patient continues to maintain many improvements. CONCLUSIONS: Anodal tDCS to the rTPJ may represent an effective treatment for improving social functioning in ASD, with a larger clinical trial needed to validate this effect.