Transcranial Direct Current Stimulation Facilitates Associative Learning and Alters Functional Connectivity in the Primate Brain.

There has been growing interest in transcranial direct current stimulation (tDCS), a non-invasive technique purported to modulate neural activity via weak, externally applied electric fields. Although some promising preliminary data have been reported for applications ranging from stroke rehabilitation to cognitive enhancement, little is known about how tDCS affects the human brain, and some studies have concluded that it may have no effect at all. Here, we describe a macaque model of tDCS that allows us to simultaneously examine the effects of tDCS on brain activity and behavior. We find that applying tDCS to right prefrontal cortex improves monkeys' performance on an associative learning task. While firing rates do not change within the targeted area, tDCS does induce large low-frequency oscillations in the underlying tissue. These oscillations alter functional connectivity, both locally and between distant brain areas, and these long-range changes correlate with tDCS's effects on behavior. Together, these results are consistent with the idea that tDCS leads to widespread changes in brain activity and suggest that it may be a valuable method for cheaply and non-invasively altering functional connectivity in humans.

Using precise word timing information improves decoding accuracy in a multiband-accelerated multimodal reading experiment.

The blood-oxygen-level-dependent (BOLD) signal measured in functional magnetic resonance imaging (fMRI) experiments is generally regarded as sluggish and poorly suited for probing neural function at the rapid timescales involved in sentence comprehension. However, recent studies have shown the value of acquiring data with very short repetition times (TRs), not merely in terms of improvements in contrast to noise ratio (CNR) through averaging, but also in terms of additional fine-grained temporal information. Using multiband-accelerated fMRI, we achieved whole-brain scans at 3-mm resolution with a TR of just 500 ms at both 3T and 7T field strengths. By taking advantage of word timing information, we found that word decoding accuracy across two separate sets of scan sessions improved significantly, with better overall performance at 7T than at 3T. The effect of TR was also investigated; we found that substantial word timing information can be extracted using fast TRs, with diminishing benefits beyond TRs of 1000 ms.

Transcranial Direct Current Stimulation Modulates Neuronal Activity and Learning in Pilot Training.

Skill acquisition requires distributed learning both within (online) and across (offline) days to consolidate experiences into newly learned abilities. In particular, piloting an aircraft requires skills developed from extensive training and practice. Here, we tested the hypothesis that transcranial direct current stimulation (tDCS) can modulate neuronal function to improve skill learning and performance during flight simulator training of aircraft landing procedures. Thirty-two right-handed participants consented to participate in four consecutive daily sessions of flight simulation training and received sham or anodal high-definition-tDCS to the right dorsolateral prefrontal cortex (DLPFC) or left motor cortex (M1) in a randomized, double-blind experiment. Continuous electroencephalography (EEG) and functional near infrared spectroscopy (fNIRS) were collected during flight simulation, n-back working memory, and resting-state assessments. tDCS of the right DLPFC increased midline-frontal theta-band activity in flight and n-back working memory training, confirming tDCS-related modulation of brain processes involved in executive function. This modulation corresponded to a significantly different online and offline learning rates for working memory accuracy and decreased inter-subject behavioral variability in flight and n-back tasks in the DLPFC stimulation group. Additionally, tDCS of left M1 increased parietal alpha power during flight tasks and tDCS to the right DLPFC increased midline frontal theta-band power during n-back and flight tasks. These results demonstrate a modulation of group variance in skill acquisition through an increasing in learned skill consistency in cognitive and real-world tasks with tDCS. Further, tDCS performance improvements corresponded to changes in electrophysiological and blood-oxygenation activity of the DLPFC and motor cortices, providing a stronger link between modulated neuronal function and behavior.

Investigation of Biases and Compensatory Strategies Using a Probabilistic Variant of the Wisconsin Card Sorting Test.

The Wisconsin Card Sorting Test (WCST) evaluates a subject's ability to shift to a new pattern of behavior in response to the presentation of unexpected negative feedback. The present study introduces a novel version of the traditional WCST by integrating a probabilistic component into its traditional rule shifting to add uncertainty to the task, as well as the option to forage for information during any particular trial. These changes transformed a task that is trivial for neurotypical individuals into a challenging environment useful for evaluating biases and compensatory strategizing. Sixty subjects performed the probabilistic WCST at four uncertainty levels to determine the effect of uncertainty on subject performance and strategy. Results revealed that increasing the level of uncertainty during a run of trials correlated with a reduction in rational strategizing in favor of both random choice and information foraging, evoking biases and suboptimal strategies such as satisfaction of search, negativity bias, and probability matching.

Respiration drives network activity and modulates synaptic and circuit processing of lateral inhibition in the olfactory bulb.

Respiration produces rhythmic activity in the entire olfactory system, driving neurons in the olfactory epithelium, olfactory bulb (OB), and cortex. The rhythmic nature of this activity is believed to be a critical component of sensory processing. OB projection neurons, mitral and tufted cells exhibit both spiking and subthreshold membrane potential oscillations rhythmically coupled to respiration. However, the network and synaptic mechanisms that produce respiration-coupled activity, and the effects of respiration on lateral inhibition, a major component of sensory processing in OB circuits, are not known. Is respiration-coupled activity in mitral and tufted cells produced by sensory synaptic inputs from nasal airflow alone, cortico-bulbar feedback, or intrinsic membrane properties of the projection neurons? Does respiration facilitate or modulate the activity of inhibitory lateral circuits in the OB? Here, in vivo intracellular recordings from identified mitral and tufted cells in anesthetized rats demonstrate that nasal airflow provides excitatory synaptic inputs to both cell types and drives respiration-coupled spiking. Lateral inhibition, inhibitory postsynaptic potentials evoked by intrabulbar microstimulation, was modulated by respiration. In individual mitral and tufted cells, inhibition was larger at specific respiratory phases. However, lateral inhibition was not uniformly larger during a particular respiratory phase in either cell type. Removing nasal airflow abolished respiration-coupled spiking in both cell types and nearly eliminated spiking in mitral, but not tufted, cells. In the absence of nasal airflow, lateral inhibition was weaker in mitral cells and less modulated in tufted cells. Thus, respiration drives distinct network activities that functionally modulate sensory processing in the OB.

Lateral Connectivity in the Olfactory Bulb is Sparse and Segregated.

Lateral connections in the olfactory bulb were previously thought to be organized for center-surround inhibition. However, recent anatomical and physiological studies showed sparse and distributed interactions of inhibitory granule cells (GCs) which tended to be organized in columnar clusters. Little is known about how these distributed clusters are interconnected. In this study, we use transsynaptic tracing viruses bearing green or red fluorescent proteins to further elucidate mitral- and tufted-to-GC connectivity. Separate sites in the glomerular layer were injected with each virus. Columns with labeling from both viruses after transsynaptic spread show sparse red or green GCs which tended to be segregated. However, there was a higher incidence of co-labeled cells than chance would predict. Similar segregation of labeling is observed from dual injections into olfactory cortex. Collectively, these results suggest that neighboring mitral and tufted cells receive inhibitory inputs from segregated subsets of GCs, enabling inhibition of a center by specific and discontinuous lateral elements.