Transcranial alternating current stimulation affects the BOLD signal in a frequency and task-dependent manner.

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for manipulating ongoing brain oscillations. While previous studies demonstrated frequency-specific effects of tACS on diverse cognitive functions, its effect on neural activity remains poorly understood. Here we asked how tACS modulates regional fMRI blood oxygenation level dependent (BOLD) signal as a function of frequency, current strength, and task condition. TACS was applied over the posterior cortex of healthy human subjects while the BOLD signal was measured during rest or task conditions (visual perception, passive video viewing and motor task). TACS was applied in a blockwise manner at different frequencies (10, 16, 60 and 80 Hz). The strongest tACS effects on BOLD activity were observed with stimulation at alpha (10 Hz) and beta (16 Hz) frequency bands, while effects of tACS at the gamma range were rather modest. Specifically, we found that tACS at 16 Hz induced BOLD activity increase in fronto-parietal areas. Overall, tACS effects varied as a function of frequency and task, and were predominantly seen in regions that were not activated by the task. Also, the modulated regions were poorly predicted by current density modeling studies. Taken together, our results suggest that tACS does not necessarily exert its strongest effects in regions below the electrodes and that region specificity might be achieved with tACS due to varying susceptibility of brain regions to entrain to a given frequency.

Lesions affecting the right hippocampal formation differentially impair short-term memory of spatial and nonspatial associations.

Converging evidence from behavioral and imaging studies suggests that within the human medial temporal lobe (MTL) the hippocampal formation may be particularly involved in recognition memory of associative information. However, it is unclear whether the hippocampal formation processes all types of associations or whether there is a specialization for processing of associations involving spatial information. Here, we investigated this issue in six patients with postsurgical lesions of the right MTL affecting the hippocampal formation and in ten healthy controls. Subjects performed a battery of delayed match-to-sample tasks with two delays (900/5,000 ms) and three set sizes. Subjects were requested to remember either single features (colors, locations, shapes, letters) or feature associations (color-location, color-shape, color-letter). In the single-feature conditions, performance of patients did not differ from controls. In the association conditions, a significant delay-dependent deficit in memory of color-location associations was found. This deficit was largely independent of set size. By contrast, performance in the color-shape and color-letter conditions was normal. These findings support the hypothesis that a region within the right MTL, presumably the hippocampal formation, does not equally support all kinds of visual memory but rather has a bias for processing of associations involving spatial information. Recruitment of this region during memory tasks appears to depend both on processing type (associative/nonassociative) and to-be-remembered material (spatial/nonspatial).

Aberrant functional connectivity of resting state networks related to misperceptions and intra-individual variability in Parkinson's disease.

Patients with Parkinson's disease (PD) frequently suffer from visual misperceptions and hallucinations, which are difficult to objectify and quantify. We aimed to develop an image recognition task to objectify misperceptions and to assess performance fluctuations in PD patients with and without self-reported hallucinations. Thirty-two non-demented patients with Parkinson's disease (16 with and 16 without self-reported visual hallucinations) and 25 age-matched healthy controls (HC) were tested. Participants performed a dynamic image recognition task with real and scrambled images. We assessed misperception scores and intra-individual variability in recognition times. To gain insight into possible neural mechanisms related to misperceptions and performance fluctuations we correlated resting state network connectivity to the behavioral outcomes in a subsample of Parkinson's disease patients (N = 16). We found that PD patients with self-reported hallucinations (PD-VH) exhibited higher perceptual error rates, due to decreased perceptual sensitivity and not due to changed decision criteria. In addition, PD-VH patients exhibited higher intra-individual variability in recognition times than HC or PD-nonVH patients. Both, misperceptions and intra-individual variability were negatively correlated with resting state functional connectivity involving frontal and parietal brain regions, albeit in partly different subregions. Consistent with previous research suggesting that hallucinations arise from dysfunction in attentional networks, misperception scores correlated with reduced functional connectivity between the dorsal attention and salience network. Intra-individual variability correlated with decreased connectivity between somatomotor and right fronto-parietal networks. We conclude that our task can detect visual misperceptions that are more prevalent in PD-VH patients. In addition, fluctuating visual performance appear to be a signature of PD-VH patients, which might assist further studies of the underlying pathophysiological mechanisms and cognitive processes.

Modulation of Long-Range Connectivity Patterns via Frequency-Specific Stimulation of Human Cortex.

There is increasing interest in how the phase of local oscillatory activity within a brain area determines the long-range functional connectivity of that area. For example, increasing convergent evidence from a range of methodologies suggests that beta (20 Hz) oscillations may play a vital role in the function of the motor system [1-5]. The "communication through coherence" hypothesis posits that the precise phase of coherent oscillations in network nodes is a determinant of successful communication between them [6, 7]. Here we set out to determine whether oscillatory activity in the beta band serves to support this theory within the cortical motor network in vivo. We combined non-invasive transcranial alternating-current stimulation (tACS) [8-12] with resting-state functional MRI (fMRI) [13] to follow both changes in local activity and long-range connectivity, determined by inter-areal blood-oxygen-level-dependent (BOLD) signal correlation, as a proxy for communication in the human cortex. Twelve healthy subjects participated in three fMRI scans with 20 Hz, 5 Hz, or sham tACS applied separately on each scan. Transcranial magnetic stimulation (TMS) at beta frequency has previously been shown to increase local activity in the beta band [14] and to modulate long-range connectivity within the default mode network [15]. We demonstrated that beta-frequency tACS significantly changed the connectivity pattern of the stimulated primary motor cortex (M1), without changing overall local activity or network connectivity. This finding is supported by a simple phase-precession model, which demonstrates the plausibility of the results and provides emergent predictions that are consistent with our empirical findings. These findings therefore inform our understanding of how local oscillatory activity may underpin network connectivity.

Simultaneous Transcranial Alternating Current Stimulation and Functional Magnetic Resonance Imaging.

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations. TACS employs frequency-specific stimulation of the human brain through current applied to the scalp with surface electrodes. Most current knowledge of the technique is based on behavioral studies; thus, combining the method with brain imaging holds potential to better understand the mechanisms of tACS. Because of electrical and susceptibility artifacts, combining tACS with brain imaging can be challenging, however, one brain imaging technique that is well suited to be applied simultaneously with tACS is functional magnetic resonance imaging (fMRI). In our lab, we have successfully combined tACS with simultaneous fMRI measurements to show that tACS effects are state, current, and frequency dependent, and that modulation of brain activity is not limited to the area directly below the electrodes. This article describes a safe and reliable setup for applying tACS simultaneously with visual task fMRI studies, which can lend to understanding oscillatory brain function as well as the effects of tACS on the brain.