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Over the last decades, the treatment of schizophrenia has shifted fundamentally from a focus on symptom reduction to a focus on recovery and improving aspects of functioning. In this study, we examined the effect of transcranial direct current stimulation (tDCS) on social cognitive and nonsocial neurocognitive functions, as well as on electroencephalogram (EEG) measures, in individuals with schizophrenia. Thirty-seven individuals with schizophrenia were administered one of three different tDCS conditions (cathodal, anodal, and sham) per visit over the course of three visits, with approximately one week between each visit. Order of conditions was randomized and counterbalanced across subjects. For the active conditions, the electrode was placed over the left dorsolateral prefrontal cortex with the reference electrode over right supraorbital cortex. Current intensity was 2 mA and was maintained for two 20-minute sessions, with a one hour break between the sessions. Assessments were conducted immediately following each session, in a counterbalanced order of administration. No systematic effects were found across the social and nonsocial cognitive domains, and no significant effects were detected on event-related potentials (ERPs). The very small effect sizes, further validated by post-hoc power analyses (large Critical Ns), demonstrated that these findings were not due to lack of statistical power. Except for mild local discomfort, no significant side effects were reported. Findings demonstrate the safety and ease of administration of this procedure, but suggest that a single dose of tDCS over these areas does not yield a therapeutic effect on cognition in schizophrenia. ClinicalTrials.gov NCT02539797.

Transcranial ultrasound stimulation (tUS) shows potential as a noninvasive brain stimulation (NIBS) technique, offering increased spatial precision compared to other NIBS techniques. However, its reported effects on primary motor cortex (M1) are limited. We aimed to better understand tUS effects in human M1 by performing tUS of the hand area of M1 (M1 hand ) during tonic muscle contraction of the index finger. Stimulation during muscle contraction was chosen because of the transcranial magnetic stimulation-induced phenomenon known as cortical silent period (cSP), in which transcranial magnetic stimulation (TMS) of M1 hand involuntarily suppresses voluntary motor activity. Since cSP is widely considered an inhibitory phenomenon, it presents an ideal parallel for tUS, which has often been proposed to preferentially influence inhibitory interneurons. Recording electromyography (EMG) of the first dorsal interosseous (FDI) muscle, we investigated effects on muscle activity both during and after tUS. We found no change in FDI EMG activity concurrent with tUS stimulation. Using single-pulse TMS, we found no difference in M1 excitability before versus after sparsely repetitive tUS exposure. Using acoustic simulations in models made from structural MRI of the participants that matched the experimental setups, we estimated in-brain pressures and generated an estimate of cumulative tUS exposure experienced by M1 hand for each subject. We were unable to find any correlation between cumulative M1 hand exposure and M1 excitability change. We also present data that suggest a TMS-induced MEP always preceded a near-threshold cSP.

Increasing contextual interference (CI) during practice benefits learning, making it a desirable difficulty. For example, interleaved practice (IP) of motor sequences is generally more difficult than repetitive practice (RP) during practice but leads to better learning. Here we investigated whether CI in practice modulated resting-state functional connectivity during consolidation. 26 healthy adults (11 men/15 women, age = 23.3 ± 1.3 years) practiced two sets of three sequences in an IP or RP condition over 2 days, followed by a retention test on Day 5 to evaluate learning. On each practice day, functional magnetic resonance imaging (fMRI) data were acquired during practice and also in a resting state immediately after practice. The resting-state fMRI data were processed using independent component analysis (ICA) followed by functional connectivity analysis, showing that IP on Day 1 led to greater resting connectivity than RP between the left premotor cortex and left dorsolateral prefrontal cortex (DLPFC), bilateral posterior cingulate cortices, and bilateral inferior parietal lobules. Moreover, greater resting connectivity after IP than RP on Day 1, between the left premotor cortex and the hippocampus, amygdala, putamen, and thalamus on the right, and the cerebellum, was associated with better learning following IP. Mediation analysis further showed that the association between enhanced resting premotor-hippocampal connectivity on Day 1 and better retention performance following IP was mediated by greater task-related functional activation during IP on Day 2. Our findings suggest that the benefit of CI to motor learning is likely through enhanced resting premotor connectivity during the early phase of consolidation. [Display omitted] •Introducing contextual interference (CI) in practice benefits motor learning.•High-CI practice enhanced resting brain connectivity immediately after practice.•Enhanced brain connectivity after high-CI practice was linked to better learning.

Parkinson’s disease (PD) is a neurodegenerative disease with both genetic and environmental risk factors. Efforts to understand the growing incidence and prevalence of PD have led to several state PD registry initiatives in the United States. The California PD Registry (CPDR) is the largest state-wide PD registry and requires electronic reporting of all eligible cases by all medical providers. We borrow from our experience with the CPDR to highlight 4 gaps to population-based PD registries. Specifically we address (1) who should be included in PD registries; (2) what data should be collected in PD case reports; (3) how to ensure the validity of case reports; and (4) how can state PD registries exchange and aggregate information. We propose a set of recommendations that addresses these and other gaps toward achieving a promise of a practical, interoperable, and scalable PD registry in the U.S., which can serve as a key health information resource to support epidemiology, health equity, quality improvement, and research.

What is the relationship between language and complex thought? In the context of deductive reasoning there are two main views. Under the first, which we label here the language-centric view, language is central to the syntax-like combinatorial operations of complex reasoning. Under the second, which we label here the language-independent view, these operations are dissociable from the mechanisms of natural language. We applied continuous theta burst stimulation (cTBS), a form of noninvasive neuromodulation, to healthy adult participants to transiently inhibit a subregion of Broca’s area (left BA44) associated in prior work with parsing the syntactic relations of natural language. We similarly inhibited a subregion of dorsomedial frontal cortex (left medial BA8) which has been associated with core features of logical reasoning. There was a significant interaction between task and stimulation site. Post hoc tests revealed that performance on a linguistic reasoning task, but not deductive reasoning task, was significantly impaired after inhibition of left BA44, and performance on a deductive reasoning task, but not linguistic reasoning task, was decreased after inhibition of left medial BA8 (however not significantly). Subsequent linear contrasts supported this pattern. These novel results suggest that deductive reasoning may be dissociable from linguistic processes in the adult human brain, consistent with the language-independent view.

Electronic Health Record (EHR) systems are often configured to address challenges and improve patient safety for persons with Parkinson’s disease (PWP). For example, EHR systems can help identify Parkinson’s disease (PD) patients across the hospital by flagging a patient’s diagnosis in their chart, preventing errors in medication and dosing through the use of clinical decision support, and supplementing staff education through care plans that provide step-by-step road maps for disease-based care of a specific patient population. However, most EHR-based solutions are locally developed and, thus, difficult to scale widely or apply uniformly across hospital systems. In 2020, the Parkinson’s Foundation, a national and international leader in PD research, education, and advocacy, and Epic, a leading EHR vendor with more than 35% market share in the United States, launched a partnership to reduce risks to hospitalized PWP using standardized EHR-based solutions. This article discusses that project which included leadership from physician informaticists, movement disorders specialists, hospital quality officers, the Parkinson’s Foundation and members of the Parkinson’s community. We describe the best practice solutions developed through this project. We highlight those that are currently available as standard defaults or options within the Epic EHR, discuss the successes and limitations of these solutions, and consider opportunities for scalability in environments beyond a single EHR vendor. The Parkinson’s Foundation and Epic launched a partnership to develop best practice solutions in the Epic EHR system to improve safety for PWP in the hospital. The goal of the partnership was to create the EHR tools that will have the greatest impact on outcomes for hospitalized PWP.

People all over the world use their hands to communicate expressively. Autonomous gestures, also known as emblems, are highly social in nature, and convey conventionalized meaning without accompanying speech. To study the neural bases of cross-cultural social communication, we used single pulse transcranial magnetic stimulation (TMS) to measure corticospinal excitability (CSE) during observation of culture-specific emblems. Foreign Nicaraguan and familiar American emblems as well as meaningless control gestures were performed by both a Euro-American and a Nicaraguan actor. Euro-American participants demonstrated higher CSE during observation of the American compared to the Nicaraguan actor. This motor resonance phenomenon may reflect ethnic and cultural ingroup familiarity effects. However, participants also demonstrated a nearly significant (p = 0.053) actor by emblem interaction whereby both Nicaraguan and American emblems performed by the American actor elicited similar CSE, whereas Nicaraguan emblems performed by the Nicaraguan actor yielded higher CSE than American emblems. The latter result cannot be interpreted simply as an effect of ethnic ingroup familiarity. Thus, a likely explanation of these findings is that motor resonance is modulated by interacting biological and cultural factors.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising noninvasive cortical stimulation methods for adjunctive treatment of movement disorders. They avoid surgical risks and provide theoretical advantages of specific neural circuit neuromodulation. Neuromodulatory effects depend on extrinsic stimulation factors (cortical target, frequency, intensity, duration, number of sessions), intrinsic patient factors (disease process, individual variability and symptoms, state of medication treatment), and outcome measures. Most studies to date have shown beneficial effects of rTMS or tDCS on clinical symptoms in Parkinson’s disease (PD) and support the notion of spatial specificity to the effects on motor and nonmotor symptoms. Stimulation parameters have varied widely, however, and some studies are poorly controlled. Studies of rTMS or tDCS in dystonia have provided abundant data on physiology, but few on clinical effects. Multiple mechanisms likely contribute to the clinical effects of rTMS and tDCS in movement disorders, including normalization of cortical excitability, rebalancing of distributed neural network activity, and induction of dopamine release. It remains unclear how to individually adjust rTMS or tDCS factors for the most beneficial effects on symptoms of PD or dystonia. Nonetheless, the noninvasive nature, minimal side effects, positive effects in preliminary clinical studies, and increasing evidence for rational mechanisms make rTMS and tDCS attractive for ongoing investigation.

Practice of tasks in an interleaved order generally induces superior retention compared to practicing in a repetitive order. Younger and older adults practiced serial reaction time tasks that were arranged in a repeated or an interleaved order on 2 successive days. Retention was tested on Day 5. For both groups, reaction times in the interleaved condition were slower than the repetitive condition during practice, but the reverse was true during retention on Day 5. After interleaved practice, changes in M1 excitability measured by paired-pulse TMS were greater than after repetitive practice, and this effect was more pronounced in older adults. Moreover, the increased M1 excitability correlated with the benefit of interleaved practice. BOLD signal was also increased for interleaved compared to repetitive practice in both groups. However, the pattern of correlations between increased BOLD during practice and subsequent benefit of the interleaved condition differed by group. In younger adults, dorsolateral-prefrontal activity during practice was related to this benefit, while in older adults, activation in sensorimotor regions and rostral prefrontal cortex during practice correlated with the benefit of interleaving on retention. Older adults may engage compensatory mechanisms during interleaved practice such as increasing sensorimotor recruitment which in turn benefits learning.

The cerebellum has been shown to be important for skill learning, including the learning of motor sequences. We investigated whether cerebellar transcranial direct current stimulation (tDCS) would enhance learning of fine motor sequences. Because the ability to generalize or transfer to novel task variations or circumstances is a crucial goal of real world training, we also examined the effect of tDCS on performance of novel sequences after training. In Study 1, participants received either anodal, cathodal or sham stimulation while simultaneously practising three eight-element key press sequences in a non-repeating, interleaved order. Immediately after sequence practice with concurrent tDCS, a transfer session was given in which participants practised three interleaved novel sequences. No stimulation was given during transfer. An inhibitory effect of cathodal tDCS was found during practice, such that the rate of learning was slowed in comparison to the anodal and sham groups. In Study 2, participants received anodal or sham stimulation and a 24 h delay was added between the practice and transfer sessions to reduce mental fatigue. Although this consolidation period benefitted subsequent transfer for both tDCS groups, anodal tDCS enhanced transfer performance. Together, these studies demonstrate polarity-specific effects on fine motor sequence learning and generalization. This article is part of the themed issue ‘New frontiers for statistical learning in the cognitive sciences’.