Michael A. Hunter

Baseline effects of transcranial direct current stimulation on glutamatergic neurotransmission and large-scale network connectivity

Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain׳s neural architecture, from the micro to macro scales, have yet to be investigated. Using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy ((1)H MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-state networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. (1)H MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t-tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal-parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia (p<0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. The observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders.

Tracking the neuroplastic changes associated with transcranial direct current stimulation: a push for multimodal imaging

The human brain operates through an intricate balance of excitatory and inhibitory processes. Transcranial direct current stimulation (tDCS) is a non-invasive technique that is generally assumed to work by increasing the level of brain activity near the anode (positive polarity), while decreasing it near the cathode (negative polarity). However, this is based in part on untested assumptions: the exact (cellular and synaptic) inhibitory or excitatory processes that are targeted preferentially using either polarity is still an open area of research. Furthermore, the relationship between electrode polarity and membrane excitability is highly contingent upon stimulation parameters (e.g., montage, intensity, cognitive task, etc.). Although neuroimaging has been utilized to verify these general effects in the brain, further development is needed to advance our understanding of the mechanisms by which tDCS produces changes across different levels of the nervous system. To date, tDCS has produced reliable changes in neurometabolite concentration using magnetic resonance spectroscopy (MRS; Rango et al., 2008; Stagg et al., 2009; Clark et al., 2011); whole-brain functional connectivity using functional magnetic resonance imaging (fMRI; Baudewig et al., 2001; Kwon et al., 2008; Polania et al., 2011a, 2012; Pena-Gomez et al., 2012; Sehm et al., 2012, 2013; Park et al., 2013; see Turi et al., 2012 for review); and neural oscillations and event-related potentials using electroencephalography (EEG; Keeser et al., 2011; Polania et al., 2011b; Jacobson et al., 2012) or magnetocenphalography (MEG; Venkatakrishnan et al., 2011). While each of these imaging techniques provides information at specific levels within the brains neural architecture, from the micro-scales (e.g., neuro-metabolites) to the macro-scales (e.g., population-level neural synchronization), no study has combined more than one imaging modality with tDCS in order to track neuroplastic changes across these different scales. In this Opinion Article, we briefly summarize the progress made on tracking tDCS-induced neuroplastic changes using single imaging modalities (specifically MRS, fMRI, and EEG). We then demonstrate the need for multimodal imaging, with the goal of establishing a more comprehensive examination of both local and global neuroplastic changes due to tDCS. Such a design would enable measurements of brain chemistry and large-scale functional connectivity within the same subject and tDCS session, thus capturing interactions of these measures that may account for significant variability in cognition and behavior.

Cortical thickness as a contributor to abnormal oscillations in schizophrenia

Introduction Although brain rhythms depend on brain structure (e.g., gray and white matter), to our knowledge associations between brain oscillations and structure have not been investigated in healthy controls (HC) or in individuals with schizophrenia (SZ). Observing function–structure relationships, for example establishing an association between brain oscillations (defined in terms of amplitude or phase) and cortical gray matter, might inform models on the origins of psychosis. Given evidence of functional and structural abnormalities in primary/secondary auditory regions in SZ, the present study examined how superior temporal gyrus (STG) structure relates to auditory STG low-frequency and 40 Hz steady-state activity. Given changes in brain activity as a function of age, age-related associations in STG oscillatory activity were also examined. Methods Thirty-nine individuals with SZ and 29 HC were recruited. 40 Hz amplitude-modulated tones of 1 s duration were presented. MEG and T1-weighted sMRI data were obtained. Using the sources localizing 40 Hz evoked steady-state activity (300 to 950 ms), left and right STG total power and inter-trial coherence were computed. Time–frequency group differences and associations with STG structure and age were also examined. Results Decreased total power and inter-trial coherence in SZ were observed in the left STG for initial post-stimulus low-frequency activity (~ 50 to 200 ms, ~ 4 to 16 Hz) as well as 40 Hz steady-state activity (~ 400 to 1000 ms). Left STG 40 Hz total power and inter-trial coherence were positively associated with left STG cortical thickness in HC, not in SZ. Left STG post-stimulus low-frequency and 40 Hz total power were positively associated with age, again only in controls. Discussion Left STG low-frequency and steady-state gamma abnormalities distinguish SZ and HC. Disease-associated damage to STG gray matter in schizophrenia may disrupt the age-related left STG gamma-band function–structure relationships observed in controls.

Lateralized abnormalities in auditory M50 sensory gating and cortical thickness of the superior temporal gyrus in post-traumatic stress disorder: Preliminary results

Auditory sensory gating deficits have been reported in subjects with post-traumatic stress disorder (PTSD), but the hemispheric and neuronal origins of this deficit are not well understood. The objectives of this study were to: (1) investigate auditory sensory gating of the 50-ms response (M50) in patients diagnosed with PTSD by utilizing magnetoencephalography (MEG); (2) explore the relationship between M50 sensory gating and cortical thickness of the superior temporal gyrus (STG) measured with structural magnetic resonance imaging (MRI); and (3) examine the association between PTSD symptomatology and bilateral sensory gating. Seven participants with combat-related PTSD and eleven controls underwent the paired-click sensory gating paradigm. MEG localized M50 neuronal generators to the STG in both groups. The PTSD group displayed impaired M50 gating in the right hemisphere. Thinner right STG cortical thickness was associated with worse right sensory gating in the PTSD group. The right S1 M50 source strength and gating ratio were correlated with PTSD symptomatology. These findings suggest that the structural integrity of right hemisphere STG cortices play an important role in auditory sensory gating deficits in PTSD.

Frontal and superior temporal auditory processing abnormalities in schizophrenia

Background Although magnetoencephalography (MEG) studies show superior temporal gyrus (STG) auditory processing abnormalities in schizophrenia at 50 and 100 ms, EEG and corticography studies suggest involvement of additional brain areas (e.g., frontal areas) during this interval. Study goals were to identify 30 to 130 ms auditory encoding processes in schizophrenia (SZ) and healthy controls (HC) and group differences throughout the cortex. Methods The standard paired-click task was administered to 19 SZ and 21 HC subjects during MEG recording. Vector-based Spatial–temporal Analysis using L1-minimum-norm (VESTAL) provided 4D maps of activity from 30 to 130 ms. Within-group t-tests compared post-stimulus 50 ms and 100 ms activity to baseline. Between-group t-tests examined 50 and 100 ms group differences. Results Bilateral 50 and 100 ms STG activity was observed in both groups. HC had stronger bilateral 50 and 100 ms STG activity than SZ. In addition to the STG group difference, non-STG activity was also observed in both groups. For example, whereas HC had stronger left and right inferior frontal gyrus activity than SZ, SZ had stronger right superior frontal gyrus and left supramarginal gyrus activity than HC. Conclusions Less STG activity was observed in SZ than HC, indicating encoding problems in SZ. Yet auditory encoding abnormalities are not specific to STG, as group differences were observed in frontal and SMG areas. Thus, present findings indicate that individuals with SZ show abnormalities in multiple nodes of a concurrently activated auditory network.

Enhanced working memory performance via transcranial direct current stimulation: The possibility of near and far transfer

Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In each experiment, participants received either active (2.0mA) or sham (0.1mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). In Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used.

Frontal slow-wave activity as a predictor of negative symptoms, cognition and functional capacity in schizophrenia

BACKGROUND Increased temporal and frontal slow-wave delta (1-4 Hz) and theta (4-7 Hz) activities are the most consistent resting-state neural abnormalities reported in schizophrenia. The frontal lobe is associated with negative symptoms and cognitive abilities such as attention, with negative symptoms and impaired attention associated with poor functional capacity. AIMS To establish whether frontal dysfunction, as indexed by slowing, would be associated with functional impairments. METHOD Eyes-closed magnetoencephalography data were collected in 41 participants with schizophrenia and 37 healthy controls, and frequency-domain source imaging localised delta and theta activity. RESULTS Elevated delta and theta activity in right frontal and right temporoparietal regions was observed in the schizophrenia v. CONTROL GROUP In schizophrenia, right-frontal delta activity was uniquely associated with negative but not positive symptoms. In the full sample, increased right-frontal delta activity predicted poorer attention and functional capacity. CONCLUSIONS Our findings suggest that treatment-associated decreases in slow-wave activity could be accompanied by improved functional outcome and thus better prognosis.

By our bootstraps: Comparing methods for measuring auditory 40 Hz steady-state neural activity

Although the 40 Hz auditory steady-state response (ASSR) is of clinical interest, the construct validity of EEG and MEG measures of 40 Hz ASSR cortical microcircuits is unclear. This study evaluated several MEG and EEG metrics by leveraging findings of (a) an association between the 40 Hz ASSR and age in the left but not right hemisphere, and (b) right- > left-hemisphere differences in the strength of the 40 Hz ASSR. The contention is that, if an analysis method does not demonstrate a left 40 Hz ASSR and age relationship or hemisphere differences, then the obtained measures likely have low validity. Fifty-three adults were presented 500 Hz stimuli modulated at 40 Hz while MEG and EEG were collected. ASSR activity was examined as a function of phase similarity (intertrial coherence) and percent change from baseline (total power). A variety of head models (spherical and realistic) and a variety of dipole source modeling strategies (dipole source localization and dipoles fixed to Heschls gyri) were compared. Several sensor analysis strategies were also tested. EEG sensor measures failed to detect left 40 Hz ASSR and age associations or hemisphere differences. A comparison of MEG and EEG head-source models showed similarity in the 40 Hz ASSR measures and in estimating age and left 40 Hz ASSR associations, indicating good construct validity across models. Given a goal of measuring the 40 Hz ASSR cortical microcircuits, a source-modeling approach was shown to be superior in measuring this construct versus methods that rely on EEG sensor measures.

Functional connectivity within and between intrinsic brain networks correlates with trait mind wandering.

&NA; Individual differences across a variety of cognitive processes are functionally associated with individual differences in intrinsic networks such as the default mode network (DMN). The extent to which these networks correlate or anticorrelate has been associated with performance in a variety of circumstances. Despite the established role of the DMN in mind wandering processes, little research has investigated how large‐scale brain networks at rest relate to mind wandering tendencies outside the laboratory. Here we examine the extent to which the DMN, along with the dorsal attention network (DAN) and frontoparietal control network (FPCN) correlate with the tendency to mind wander in daily life. Participants completed the Mind Wandering Questionnaire and a 5‐min resting state fMRI scan. In addition, participants completed measures of executive function, fluid intelligence, and creativity. We observed significant positive correlations between trait mind wandering and 1) increased DMN connectivity at rest and 2) increased connectivity between the DMN and FPCN at rest. Lastly, we found significant positive correlations between trait mind wandering and fluid intelligence (Ravens) and creativity (Remote Associates Task). We interpret these findings within the context of current theories of mind wandering and executive function and discuss the possibility that certain instances of mind wandering may not be inherently harmful. Due to the controversial nature of global signal regression (GSReg) in functional connectivity analyses, we performed our analyses with and without GSReg and contrast the results from each set of analyses. HighlightsResting state functional connectivity was examined in several intrinsic networks.Connectivity between the DMN and FPCN positively correlated with trait mind wandering.Connectivity within the DMN positively correlated with trait mind wandering.Trait mind wandering positively correlated with fluid intelligence and creativity.

Modulating affective experience and emotional intelligence with loving kindness meditation and transcranial direct current stimulation: A pilot study

ABSTRACT Positive emotional perceptions and healthy emotional intelligence (EI) are important for social functioning. In this study, we investigated whether loving kindness meditation (LKM) combined with anodal transcranial direct current stimulation (tDCS) would facilitate improvements in EI and changes in affective experience of visual stimuli. LKM has been shown to increase positive emotional experiences and we hypothesized that tDCS could enhance these effects. Eighty-seven undergraduates were randomly assigned to 30 minutes of LKM or a relaxation control recording with anodal tDCS applied to the left dorsolateral prefrontal cortex (left dlPFC) or right temporoparietal junction (right TPJ) at 0.1 or 2.0 milliamps. The primary outcomes were self-reported affect ratings of images from the International Affective Picture System and EI as measured by the Mayer, Salovey and Caruso Emotional Intelligence Test. Results indicated no effects of training on EI, and no main effects of LKM, electrode placement, or tDCS current strength on affect ratings. There was a significant interaction of electrode placement by meditation condition (p = 0.001), such that those assigned to LKM and right TPJ tDCS, regardless of current strength, rated neutral and positive images more positively after training. Results suggest that LKM may enhance positive affective experience.