Zsolt Turi

Combining functional magnetic resonance imaging with transcranial electrical stimulation

Transcranial electrical stimulation (tES) is a neuromodulatory method with promising potential for basic research and as a therapeutic tool. The most explored type of tES is transcranial direct current stimulation (tDCS), but also transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) have been shown to affect cortical excitability, behavioral performance and brain activity. Although providing indirect measure of brain activity, functional magnetic resonance imaging (fMRI) can tell us more about the global effects of stimulation in the whole brain and what is more, on how it modulates functional interactions between brain regions, complementing what is known from electrophysiological methods such as measurement of motor evoked potentials. With this review, we aim to present the studies that have combined these techniques, the current approaches and discuss the results obtained so far.

Functional Neuroimaging and Transcranial Electrical Stimulation

Transcranial electrical stimulation (tES) is a noninvasive tool for inducing local and widespread neuroplastic changes in brain networks. The combination of tES with various neuroimaging techniques provides whole brain data on the working mechanisms of tES, in particular on the development of large-scale activation patterns of interconnected neuronal regions induced by tES. This review focuses on the combined usage of a noninvasive application of transcranial direct current stimulation and functional magnetic resonance imaging and on magnetic resonance spectroscopy.

When Size Matters: Large Electrodes Induce Greater Stimulation-related Cutaneous Discomfort Than Smaller Electrodes at Equivalent Current Density

BACKGROUND Cutaneous discomfort is typically reported during transcranial direct current stimulation (tDCS), restricting the current intensity and duration at which tDCS can be applied. It is commonly thought that current density is associated with the intensity of perceived cutaneous perception such that larger electrodes with a lower current density results in milder cutaneous sensations. OBJECTIVE The present study examined the relationship between current density, current intensity and cutaneous sensations perceived during tDCS. METHODS Two experiments were performed. In the first control experiment, the cutaneous sensations induced by varying current intensities (0.025, 0.5, 1.0 and 1.5 mA) were examined up to 10 min. These data were used for optimizing inter-stimulation intervals in the second main experiment, where participants rated the intensity, spatial size and location of the cutaneous sensations experienced during tDCS using two electrodes sizes (16 cm2 and 35 cm2). In the equivalent current density condition, the current density was kept constant under both electrodes (0.014, 0.029 and 0.043 mA/cm2), whereas in the equal current intensity condition (0.5, 1.0 and 1.5 mA) the same intensities were used for the two electrode sizes. RESULTS Large electrodes were associated with greater cutaneous discomfort when compared to smaller electrodes at a given current density. Further, levels of cutaneous perception were similar for small and large electrodes when current intensity was kept constant. CONCLUSION Cutaneous sensations during stimulation can be minimized by reducing the electrode size from 35 cm2 to 16 cm2.

Separating Recognition Processes of Declarative Memory via Anodal tDCS: Boosting Old Item Recognition by Temporal and New Item Detection by Parietal Stimulation

There is emerging evidence from imaging studies that parietal and temporal cortices act together to achieve successful recognition of declarative information; nevertheless, the precise role of these regions remains elusive. To evaluate the role of these brain areas in declarative memory retrieval, we applied bilateral tDCS, with anode over the left and cathode over the right parietal or temporal cortices separately, during the recognition phase of a verbal learning paradigm using a balanced old-new decision task. In a parallel group design, we tested three different groups of healthy adults, matched for demographic and neurocognitive status: two groups received bilateral active stimulation of either the parietal or the temporal cortex, while a third group received sham stimulation. Accuracy, discriminability index (d’) and reaction times of recognition memory performance were measurements of interest. The d’ sensitivity index and accuracy percentage improved in both active stimulation groups, as compared with the sham one, while reaction times remained unaffected. Moreover, the analysis of accuracy revealed a different effect of tDCS for old and new item recognition. While the temporal group showed enhanced performance for old item recognition, the parietal group was better at correctly recognising new ones. Our results support an active role of both of these areas in memory retrieval, possibly underpinning different stages of the recognition process.

Bi-frontal transcranial alternating current stimulation in the ripple range reduced overnight forgetting

High frequency oscillations in the hippocampal structures recorded during sleep have been proved to be essential for long-term episodic memory consolidation in both animals and in humans. The aim of this study was to test if transcranial Alternating Current Stimulation (tACS) of the dorsolateral prefrontal cortex (DLPFC) in the hippocampal ripple range, applied bi-frontally during encoding, could modulate declarative memory performance, measured immediately after encoding, and after a nights sleep. An associative word-pair learning test was used. During an evening encoding phase, participants received 1 mA 140 Hz tACS or sham stimulation over both DLPFCs for 10 min while being presented twice with a list of word-pairs. Cued recall performance was investigated 10 min after training and the morning following the training session. Forgetting from evening to morning was observed in the sham condition, but not in the 140 Hz stimulation condition. 140 Hz tACS during encoding may have an effect on the consolidation of declarative material.

Transcranial direct current stimulation over the left prefrontal cortex increases randomness of choice in instrumental learning

INTRODUCTION There is growing evidence from neuro-computational studies that instrumental learning involves the dynamic interaction of a computationally rigid, low-level striatal and a more flexible, high-level prefrontal component. METHODS To evaluate the role of the prefrontal cortex in instrumental learning, we applied anodal transcranial direct current stimulation (tDCS) optimized for the left dorsolateral prefrontal cortex, by using realistic MR-derived finite element model-based electric field simulations. In a study with a double-blind, sham-controlled, repeated-measures design, sixteen male participants performed a probabilistic learning task while receiving anodal and sham tDCS in a counterbalanced order. RESULTS Compared to sham tDCS, anodal tDCS significantly increased the amount of maladaptive shifting behavior after optimal outcomes during learning when reward probabilities were highly dissociable. Derived parameters of the Q-learning computational model further revealed a significantly increased model parameter that was sensitive to random action selection in the anodal compared to the sham tDCS session, whereas the learning rate parameter was not influenced significantly by tDCS. CONCLUSION These results congruently indicate that prefrontal tDCS during instrumental learning increased randomness of choice, possibly reflecting the influence of the cognitive prefrontal component.

Language deficits in pre-symptomatic Huntington's disease: Evidence from Hungarian

A limited number of studies have investigated language in Huntingtons disease (HD). These have generally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and morphology. Several studies of verbal inflectional morphology in English and French have reported evidence of over-active rule processing, such as over-suffixation errors (e.g., walkeded) and over-regularizations (e.g., digged). Here we extend the investigation to noun inflection in Hungarian, a Finno-Ugric agglutinative language with complex morphology, and to genetically proven pre-symptomatic Huntingtons disease (pre-HD). Although individuals with pre-HD have no clinical, motor or cognitive symptoms, the underlying pathology may already have begun, and thus sensitive behavioral measures might reveal already-present impairments. Indeed, in a Hungarian morphology production task, pre-HD patients made both over-suffixation and over-regularization errors. The findings suggest the generality of over-active rule processing in both HD and pre-HD, across languages from different families with different morphological systems, and for both verbal and noun inflection. Because the neuropathology in pre-HD appears to be largely restricted to the caudate nucleus and related structures, the findings further implicate these structures in language, and in rule-processing in particular. Finally, the need for effective treatments in HD, which will likely depend in part on the ability to sensitively measure early changes in the disease, suggests the possibility that inflectional morphology, and perhaps other language measures, may provide useful diagnostic, tracking, and therapeutic tools for assessing and treating early degeneration in pre-HD and HD.

Placebo Intervention Enhances Reward Learning in Healthy Individuals

According to the placebo-reward hypothesis, placebo is a reward-anticipation process that increases midbrain dopamine (DA) levels. Reward-based learning processes, such as reinforcement learning, involves a large part of the DA-ergic network that is also activated by the placebo intervention. Given the neurochemical overlap between placebo and reward learning, we investigated whether verbal instructions in conjunction with a placebo intervention are capable of enhancing reward learning in healthy individuals by using a monetary reward-based reinforcement-learning task. Placebo intervention was performed with non-invasive brain stimulation techniques. In a randomized, triple-blind, cross-over study we investigated this cognitive placebo effect in healthy individuals by manipulating the participants’ perceived uncertainty about the intervention’s efficacy. Volunteers in the purportedly low- and high-uncertainty conditions earned more money, responded more quickly and had a higher learning rate from monetary rewards relative to baseline. Participants in the purportedly high-uncertainty conditions showed enhanced reward learning, and a model-free computational analysis revealed a higher learning rate from monetary rewards compared to the purportedly low-uncertainty and baseline conditions. Our results indicate that the placebo response is able to enhance reward learning in healthy individuals, opening up exciting avenues for future research in placebo effects on other cognitive functions.

Perturbation of theta-gamma coupling at the temporal lobe hinders verbal declarative memory

BACKGROUND Phase-amplitude cross-frequency coupling (PAC) is characterized by the modulation of the power of a fast brain oscillation (e.g., gamma) by the phase of a slow rhythm (e.g., theta). PAC in different sub- and neocortical regions is known to underlie effective neural communication and correlates with successful long-term memory formation. OBJECTIVE/HYPOTHESIS The present work aims to extend earlier observational data, by probing the functional role of theta-gamma PAC in the left temporal cortex in humans during verbal long-term memory encoding. METHODS In three double-blinded, placebo-controlled experiments (n = 72), we employed cross-frequency transcranial alternating current stimulation (tACS) to externally modulate ongoing PAC during a verbal-associative learning task. Three types of cross-frequency tACS protocols were used: bursts of high gamma tACS were coupled to the peak or trough of the theta tACS cycle, and a control condition where gamma tACS was continuously superimposed at theta tACS cycles. RESULTS Gamma bursts coupled to the trough of theta tACS induced robust behavioral impairment in memory performance (p < .01), whereas gamma burst coupled to the peak or continuously superimposed with theta tACS had no significant behavioral effects. CONCLUSIONS Our results demonstrate direct evidence regarding the importance of theta-gamma coupling in verbal long-term memory formation.

On ways to overcome the magical capacity limit of working memory

The ability to simultaneously process and maintain multiple pieces of information is limited. Over the past 50 years, observational methods have provided a large amount of insight regarding the neural mechanisms that underpin the mental capacity that we refer to as “working memory.” More than 20 years ago, a neural coding scheme was proposed for working memory. As a result of technological developments, we can now not only observe but can also influence brain rhythms in humans. Building on these novel developments, we have begun to externally control brain oscillations in order to extend the limits of working memory.