ABSTRACT
Although previous studies have reported correlations between alpha oscillations and the "retention" subprocess of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain oscillations. Conventional transcranial alternating current stimulation (tACS) is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention subprocess). Here, we developed an online phase-corrected tACS system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits the modulation of brain oscillations at the target stimulation frequency within a short stimulation period and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to participants during the retention subprocess of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. These findings strongly support a causal link between alpha oscillations and WM retention and illustrate the broad application prospects of phase-corrected tACS.
Subject(s)
Memory, Short-Term , Transcranial Direct Current Stimulation , Humans , Memory, Short-Term/physiology , Brain/physiology , CognitionABSTRACT
Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min).
ABSTRACT
Refractive errors are associated with a range of pathological conditions, such as myopic maculopathy and glaucoma, and are highly heritable. Studies of missense and putative loss of function (pLOF) variants identified via whole exome sequencing (WES) offer the prospect of directly implicating potentially causative disease genes. We performed a genome-wide association study for refractive error in 51 624 unrelated adults, of European ancestry, aged 40-69 years from the UK and genotyped using WES. After testing 29 179 pLOF and 495 263 missense variants, 1 pLOF and 18 missense variants in 14 distinct genomic regions were taken forward for fine-mapping analysis. This yielded 19 putative causal variants of which 18 had a posterior inclusion probability >0.5. Of the 19 putative causal variants, 12 were novel discoveries. Specific variants were associated with a more myopic refractive error, while others were associated with a more hyperopic refractive error. Association with age of onset of spectacle wear (AOSW) was examined in an independent validation sample (38 100 early AOSW cases and 74 243 controls). Of 11 novel variants that could be tested, 8 (73%) showed evidence of association with AOSW status. This work identified COL4A4 and ATM as novel candidate genes associated with refractive error. In addition, novel putative causal variants were identified in the genes RASGEF1, ARMS2, BMP4, SIX6, GSDMA, GNGT2, ZNF652 and CRX. Despite these successes, the study also highlighted the limitations of community-based WES studies compared with high myopia case-control WES studies.
Subject(s)
Myopia , Refractive Errors , Adult , Exome/genetics , Genome-Wide Association Study/methods , Humans , Myopia/genetics , Neoplasm Proteins/genetics , Pore Forming Cytotoxic Proteins , Refractive Errors/genetics , Exome SequencingABSTRACT
Purpose: Emmetropization requires coordinated scaling of the major ocular components, corneal curvature and axial length. This coordination is achieved in part through a shared set of genetic variants that regulate eye size. Poorly coordinated scaling of corneal curvature and axial length results in refractive error. We tested the hypothesis that genetic variants regulating eye size in emmetropic eyes are distinct from those conferring susceptibility to refractive error. Methods: A genome-wide association study (GWAS) for corneal curvature in 22,180 adult emmetropic individuals was performed as a proxy for a GWAS for eye size. A polygenic score created using lead GWAS variants was tested for association with corneal curvature and axial length in an independent sample: 437 classified as emmetropic and 637 as ametropic. The genetic correlation between eye size and refractive error was calculated using linkage disequilibrium score regression for approximately 1 million genetic variants. Results: The GWAS for corneal curvature in emmetropes identified 32 independent genetic variants (P < 5.0e-08). A polygenic score created using these 32 genetic markers explained 3.5% (P < 0.001) and 2.0% (P = 0.001) of the variance in corneal curvature and axial length, respectively, in the independent sample of emmetropic individuals but was not predictive of these traits in ametropic individuals. The genetic correlation between eye size and refractive error was close to zero (rg = 0.00; SE = 0.06; P = 0.95). Conclusions: These results support the hypothesis that genetic variants regulating eye size in emmetropic eyes do not overlap with those conferring susceptibility to myopia. This suggests that distinct biological pathways regulate normal eye growth and myopia development.
Subject(s)
Axial Length, Eye/diagnostic imaging , Genetic Predisposition to Disease , Genome-Wide Association Study/methods , Myopia/genetics , Polymorphism, Single Nucleotide , Refraction, Ocular/physiology , Adolescent , Adult , Aged , Child , Female , Humans , Linkage Disequilibrium , Male , Middle Aged , Myopia/diagnosis , Myopia/physiopathology , Young AdultABSTRACT
Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated. Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1). Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation. Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential. Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.
ABSTRACT
The romantic relationship refers to the specific relationship in which partners are dependent upon each other to obtain satisfactory outcomes and facilitate the pursuit of their most important needs and goals. Satisfying romantic relationships is a strong predictor of better psychological well-being, better physical health, and longer life expectancy. However, romantic relationships are not all smooth-sailing and lovers are often confronted with a variety of unavoidable issues that constantly challenge the stability of their romantic relationships. Dissatisfying romantic relationships are harmful and even destructive. Dyads of lovers engage in a variety of efforts to protect and maintain their romantic relationships based on qualitative research methods including theories- and psychological consultation-based approaches. Unfortunately, those existing approaches do not seem to effectively improve romantic relationships. Thus, it is necessary to seek an efficient approach regulating dyads of lovers in romantic relationships simultaneously. Transcranial alternating current stimulation (tACS) with advantages over existing approaches satisfies this purpose. We discuss the practicability of tACS in detail, as well as why and how tACS can be utilized to improve romantic relationships. In summary, this review firstly introduced the concept of romantic relationship and the necessity of enhancing it. Then, it discussed methods to improve romantic relationships including some existing approaches. This review next discussed the practicability of using tACS to improve romantic relationships. Finally, it shone a spotlight on potential future directions for researches aiming to improve romantic relationships.